Ignite Creation Date:
2025-12-24 @ 11:33 PM
Ignite Modification Date:
2026-02-22 @ 12:39 PM
Study NCT ID:
NCT04283656
Status:
COMPLETED
Last Update Posted:
2025-03-26
First Post:
2020-02-22
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000068116', 'term': 'Gender Dysphoria'}, {'id': 'D000163', 'term': 'Acquired Immunodeficiency Syndrome'}], 'ancestors': [{'id': 'D020018', 'term': 'Sexual Dysfunctions, Psychological'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D015658', 'term': 'HIV Infections'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000592662', 'term': 'doravirine'}, {'id': 'D002191', 'term': 'Canrenoic Acid'}, {'id': 'D013148', 'term': 'Spironolactone'}, {'id': 'D004958', 'term': 'Estradiol'}], 'ancestors': [{'id': 'D011245', 'term': 'Pregnadienes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D004963', 'term': 'Estrenes'}, {'id': 'D004962', 'term': 'Estranes'}, {'id': 'D045166', 'term': 'Estradiol Congeners'}, {'id': 'D012739', 'term': 'Gonadal Steroid Hormones'}, {'id': 'D042341', 'term': 'Gonadal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Walter.Kraft@jefferson.edu', 'phone': '(215) 955-9077', 'title': 'Dr. Walter K. Kraft', 'organization': 'Thomas Jefferson University'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '9 weeks, up to 30 days after last dose of drug administered', 'description': 'Adverse events were collected throughout the duration of the study, up to 30 days after last dose of drug administered. All subjects received all treatments, and as such the comparisons are between sequences. Adverse events were not separated out by treatment, but only by Sequence. Adverse Events were monitored without regard to the specific intervention or period.', 'eventGroups': [{'id': 'EG000', 'title': 'Sequence E', 'description': 'All subjects received all treatments, and as such the comparisons are between sequences.\n\nAdverse events were not separated out by treatment, but only by Sequence\n\n4 of 8 enrolled participants were assigned to receive Sequence E, which consisted of Treatment A, B, and C administered during period I, II, and III, respectively.\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Doravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily', 'otherNumAtRisk': 4, 'deathsNumAtRisk': 4, 'otherNumAffected': 4, 'seriousNumAtRisk': 4, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Sequence F', 'description': 'All subjects received all treatments, and as such the comparisons are between sequences.\n\nAdverse events were not separated out by treatment, but only by Sequence\n\n4 of 8 enrolled participants were assigned to receive Sequence F, which consisted of Treatment C, B, and A administered during period I, II, and III, respectively.\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Doravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily', 'otherNumAtRisk': 4, 'deathsNumAtRisk': 4, 'otherNumAffected': 4, 'seriousNumAtRisk': 4, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Nausea/vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Application site erythema', 'notes': 'Tegaderm redness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Catheter site redness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Catheter site pruritus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Folliculitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Blood glucose increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Muscle spasms', 'notes': 'Muscle cramps', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Brain fog', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Migraine', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Distractibility', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Dysphoria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Irritability', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Gender dysphoria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Libido increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Mood swings', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Acne', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Hair growth abnormal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}, {'term': 'Seborrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 4, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 4, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 26.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment A', 'description': 'Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '17798.14', 'spread': '21.7', 'groupId': 'OG000'}, {'value': '18413.21', 'spread': '41.75', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '0.97', 'ciLowerLimit': '0.76', 'ciUpperLimit': '1.24', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment A (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for doravirine AUC falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Doravirine AUC derived from plasma sampling with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'hr*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Doravirine Maximum Concentration (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment A', 'description': 'Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '745.46', 'spread': '21.43', 'groupId': 'OG000'}, {'value': '799.67', 'spread': '26.01', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '0.93', 'ciLowerLimit': '0.66', 'ciUpperLimit': '1.32', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment A (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for doravirine Cmax falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Doravirine maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Doravirine Trough Concentration (C24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment A', 'description': 'Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '283.74', 'spread': '25.42', 'groupId': 'OG000'}, {'value': '292.89', 'spread': '49.3', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '0.97', 'ciLowerLimit': '0.76', 'ciUpperLimit': '1.24', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment A (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for doravirine C24 falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '24 hours post-dose for all participants', 'description': 'Doravirine observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Tenofovir Disoproxil Fumarate Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment A', 'description': 'Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '2370.6', 'spread': '23.42', 'groupId': 'OG000'}, {'value': '2031.84', 'spread': '35.25', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.17', 'ciLowerLimit': '0.91', 'ciUpperLimit': '1.50', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment A (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for tenofovir AUC falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Tenofovir AUC derived from plasma sampling with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'hr*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Tenofovir Disoproxil Fumarate Maximum Concentration (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment A', 'description': 'Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '178.84', 'spread': '58.4', 'groupId': 'OG000'}, {'value': '129.95', 'spread': '99.92', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.38', 'ciLowerLimit': '0.73', 'ciUpperLimit': '2.60', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment A (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for tenofovir Cmax falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Tenofovir maximum observed concentration during the dosing interval', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Tenofovir Disoproxil Fumarate Trough Concentration (C24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment A', 'description': 'Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '29.59', 'spread': '24.23', 'groupId': 'OG000'}, {'value': '26', 'spread': '35.77', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.14', 'ciLowerLimit': '0.93', 'ciUpperLimit': '1.40', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment A (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate alone)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for tenofovir C24 falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '24 hours post-dose for all participants', 'description': 'Tenofovir observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Estradiol Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment B', 'description': 'Treatment B: Single-dose estradiol and spironolactone co-administered with placebo\n\nSpironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '9370.25', 'spread': '14.36', 'groupId': 'OG000'}, {'value': '9677.31', 'spread': '43.29', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '0.97', 'ciLowerLimit': '0.70', 'ciUpperLimit': '1.35', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment B (Single-dose estradiol and spironolactone co-administered with placebo)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratio for estradiol AUC falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC) derived from plasma sampling', 'unitOfMeasure': 'hr*pg/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Estradiol Maximum Concentration (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment B', 'description': 'Treatment B: Single-dose estradiol and spironolactone co-administered with placebo\n\nSpironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '118.08', 'spread': '20.5', 'groupId': 'OG000'}, {'value': '105.14', 'spread': '21.26', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.12', 'ciLowerLimit': '0.92', 'ciUpperLimit': '1.36', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment B (Single-dose estradiol and spironolactone co-administered with placebo)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratios for estradiol Cmax falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Estradiol maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}, {'type': 'PRIMARY', 'title': 'Estradiol Trough Concentration (C12)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Treatment C', 'description': 'Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nDoravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily'}, {'id': 'OG001', 'title': 'Treatment B', 'description': 'Treatment B: Single-dose estradiol and spironolactone co-administered with placebo\n\nSpironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}], 'classes': [{'categories': [{'measurements': [{'value': '100.26', 'spread': '26.56', 'groupId': 'OG000'}, {'value': '92.01', 'spread': '36.94', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.09', 'ciLowerLimit': '0.88', 'ciUpperLimit': '1.35', 'pValueComment': 'A two-sided significance level of 0.05 with a mean ratio of 1 for no effect was assumed.', 'estimateComment': 'Ratio represents Treatment C (Single-dose oral doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone) over Treatment B (Single-dose estradiol and spironolactone co-administered with placebo)', 'groupDescription': '6 participants completed the study and were included in the pharmacokinetic analysis. As all participants received the same treatment groups but not necessarily in the same order, calculations were done between arms (Sequence E and F). 10 subjects was determined to achieve 80% power to reject the null hypothesis (geometric mean ratios for estradiol C12 falls outside of the no-effect boundaries) with two-sided significance level of 0.05 assuming a mean ratio of 1 for no effect.', 'nonInferiorityType': 'EQUIVALENCE', 'statisticalComment': 'A post hoc power analysis determined 80% power would be achieved for 6 subjects to detect an effect size of 1.43 or greater at 5% significance level.', 'nonInferiorityComment': 'The no-effect (bioequivalence) boundaries of 80%-125% were used.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '12 hours post-dose for all participants', 'description': 'Estradiol observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': '6 participants completed the study and were included in the pharmacokinetic analysis.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Sequence E', 'description': '4 of 8 enrolled participants were assigned to receive Sequence E, which consisted of Treatment A, B, and C administered during period I, II, and III, respectively.\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Doravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}, {'id': 'FG001', 'title': 'Sequence F', 'description': '4 of 8 enrolled participants were assigned to receive Sequence F, which consisted of Treatment C, B, and A administered during period I, II, and III, respectively.\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Doravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '4'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Participants were recruited through social media outreach and by interaction with advocacy groups. They were enrolled in the study between January 4, 2022 and September 21, 2022 at the Clinical Research Unit at Thomas Jefferson University.', 'preAssignmentDetails': '8 enrolled participants were randomized 1:1 to either Sequence E of F.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Sequence E', 'description': '4 of 8 enrolled participants were assigned to receive Sequence E, which consisted of Treatment A, B, and C administered during period I, II, and III, respectively.\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Doravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}, {'id': 'BG001', 'title': 'Sequence F', 'description': '4 of 8 enrolled participants were assigned to receive Sequence F, which consisted of Treatment C, B, and A administered during period I, II, and III, respectively.\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone Doravirine/Lamivudine/Tenofovir: 100mg/300mg/300mg orally for one dose, daily Spironolactone 100mg: 200mg orally for two doses, twice-daily Estradiol 2mg: 4mg orally for two doses, twice-daily Placebo: Placebo for one dose, daily'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '25.5', 'groupId': 'BG000', 'lowerLimit': '25', 'upperLimit': '38'}, {'value': '27', 'groupId': 'BG001', 'lowerLimit': '24', 'upperLimit': '31'}, {'value': '25.5', 'groupId': 'BG002', 'lowerLimit': '24', 'upperLimit': '38'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex/Gender, Customized', 'classes': [{'title': 'Gender Identity', 'categories': [{'title': 'Transgender female (male-to-female)', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'Transgender male (female-to-male)', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': '8 participants were enrolled in the study and randomized 1:1 to either Sequence E or F.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-12-27', 'size': 1292739, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2023-07-07T13:12', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Three period crossover'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 8}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-01-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-03', 'completionDateStruct': {'date': '2022-12-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-03-11', 'studyFirstSubmitDate': '2020-02-22', 'resultsFirstSubmitDate': '2023-07-08', 'studyFirstSubmitQcDate': '2020-02-22', 'lastUpdatePostDateStruct': {'date': '2025-03-26', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-03-11', 'studyFirstPostDateStruct': {'date': '2020-02-25', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-03-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-10-25', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Doravirine AUC derived from plasma sampling with geometric mean ratio compared between treatment arms'}, {'measure': 'Doravirine Maximum Concentration (Cmax)', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Doravirine maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms'}, {'measure': 'Doravirine Trough Concentration (C24)', 'timeFrame': '24 hours post-dose for all participants', 'description': 'Doravirine observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms'}, {'measure': 'Tenofovir Disoproxil Fumarate Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Tenofovir AUC derived from plasma sampling with geometric mean ratio compared between treatment arms'}, {'measure': 'Tenofovir Disoproxil Fumarate Maximum Concentration (Cmax)', 'timeFrame': 'Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Tenofovir maximum observed concentration during the dosing interval'}, {'measure': 'Tenofovir Disoproxil Fumarate Trough Concentration (C24)', 'timeFrame': '24 hours post-dose for all participants', 'description': 'Tenofovir observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms'}, {'measure': 'Estradiol Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)', 'timeFrame': 'Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC) derived from plasma sampling'}, {'measure': 'Estradiol Maximum Concentration (Cmax)', 'timeFrame': 'Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants', 'description': 'Estradiol maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms'}, {'measure': 'Estradiol Trough Concentration (C12)', 'timeFrame': '12 hours post-dose for all participants', 'description': 'Estradiol observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Transgender Health', 'Gender Dysphoria', 'Transgender Women', 'Human Immunodeficiency Virus']}, 'referencesModule': {'references': [{'pmid': '38421210', 'type': 'RESULT', 'citation': 'Lam K, Kraft WK, Zhan T, Lam E. Bidirectional pharmacokinetics of doravirine, tenofovir, and feminizing hormones in transgender women (IDentify): A randomized crossover trial. Clin Transl Sci. 2024 Mar;17(3):e13721. doi: 10.1111/cts.13721.'}]}, 'descriptionModule': {'briefSummary': 'Transgender women living with Human Immunodeficiency Virus (HIV) may prioritize gender-affirming hormonal therapy over antiretroviral drug therapy. Hormonal therapy typically consists of oral estradiol and spironolactone, which induce drug-metabolizing enzymes after prolonged administration. This study evaluates the bi-directional potential drug interaction between the antiretroviral drug, doravirine, when co-administered with estradiol and spironolactone.', 'detailedDescription': 'This study will consist of healthy transgender women volunteers randomized to a 1:1 sequence ("E" or "F") There are three periods and in each period there are one of three treatments\n\nTreatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone\n\nThe primary outcome measures are the drug concentrations\n\nThe primary comparisons are geometric mean ratios of drugs with potential perpetrators of drug interactions using a crossover method'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'genderBased': True, 'genderDescription': 'Transgender Female', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Healthy self-identified transgender women (male-to-female) between 18-45 years old at the time of screening\n* Have not undergone an orchiectomy\n* Receiving oral estradiol and spironolactone for \\>/= 3 months prior to study entry with a self-reported adherence to prescribed doses of \\>/= 90%\n* Agree to abstain from alcohol consumption throughout the duration of the study\n* Be willing to briefly interrupt hormonal therapy prior to and during the study\n* If on pre-exposure prophylaxis (PrEP) therapy containing tenofovir alafenamide or tenofovir disoproxil fumarate, willing to discontinue PrEP at least 2 weeks before study start and for the duration of the study\n* Agree to use condoms for all sexual activity prior to the start and throughout the duration of the study\n* Evidence of a personal signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study\n\nExclusion Criteria:\n\n* Presence of clinically significant acute or chronic disease, that in the investigator's opinion, would compromise the participant's safety during the study\n* Use of injectable or transdermal estradiol\n* Use of any other hormonal replacement therapy, wit h the exception of oral estradiol and spironolactone\n* Current use of any antiretroviral drug. This will not be exclusionary if participants reported discontinuing within 30 days of screening\n* Creatinine clearance \\</= 60 mL/min, as estimated by the Cockcroft-Gault equation\n* Known anaphylactic or severe systemic reactions to any components of doravirine, lamivudine, or tenofovir disoproxil fumarate\n* Positive HIV, hepatitis B or Hepatitis C virus at screening. Evidence of prior hepatitis B infection and immunity is not exclusionary. Positive hepatitis C antibody with negative viral load or documented antiviral hepatitis C treatment with one post treatment non-detectable hepatitis C viral load is not exclusionary\n* Recent significant blood or plasma donation"}, 'identificationModule': {'nctId': 'NCT04283656', 'acronym': 'IDENTIFY', 'briefTitle': 'Evaluating Drug Interactions Between Doravirine With Estradiol and Spironolactone in Healthy Transgender Women', 'organization': {'class': 'OTHER', 'fullName': 'Thomas Jefferson University'}, 'officialTitle': 'A Prospective, Randomized, Three-period Crossover, Interaction Study to Evaluate the Pharmacokinetics of Doravirine and Tenofovir Disoproxil Fumarate Co-administered With Cross-sex Hormonal Therapy in Adult HIV-negative Transgender Women', 'orgStudyIdInfo': {'id': '15431'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Treatment A', 'description': 'Single-dose oral Doravirine/lamivudine/tenofovir disoproxil', 'interventionNames': ['Drug: Doravirine/Lamivudine/Tenofovir']}, {'type': 'EXPERIMENTAL', 'label': 'Treatment B', 'description': 'Single-dose estradiol and spironolactone co-administered with placebo', 'interventionNames': ['Drug: Spironolactone 100mg', 'Drug: Estradiol 2mg', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Treatment C', 'description': 'Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone', 'interventionNames': ['Drug: Doravirine/Lamivudine/Tenofovir', 'Drug: Spironolactone 100mg', 'Drug: Estradiol 2mg']}], 'interventions': [{'name': 'Doravirine/Lamivudine/Tenofovir', 'type': 'DRUG', 'otherNames': ['Delstrigo'], 'description': '100mg/300mg/300mg orally for one dose, daily', 'armGroupLabels': ['Treatment A', 'Treatment C']}, {'name': 'Spironolactone 100mg', 'type': 'DRUG', 'otherNames': ['Aldactone'], 'description': '200mg orally for two doses, twice-daily', 'armGroupLabels': ['Treatment B', 'Treatment C']}, {'name': 'Estradiol 2mg', 'type': 'DRUG', 'description': '4mg orally for two doses, twice-daily', 'armGroupLabels': ['Treatment B', 'Treatment C']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Placebo for one dose, daily', 'armGroupLabels': ['Treatment B']}]}, 'contactsLocationsModule': {'locations': [{'zip': '19107', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Clinical Research Unit at Thomas Jefferson University', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'overallOfficials': [{'name': 'Walter K Kraft, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Thomas Jefferson University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Pharmacokinetic data will be updated in study outcome and results.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Thomas Jefferson University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Walter K. Kraft', 'investigatorAffiliation': 'Thomas Jefferson University'}}}}