Ignite Creation Date:
2025-12-24 @ 4:31 PM
Ignite Modification Date:
2026-01-05 @ 6:08 PM
Study NCT ID:
NCT04603066
Status:
COMPLETED
Last Update Posted:
2025-08-14
First Post:
2020-09-21
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Tariquidar-ondansetron Combination in Neuropathic Pain
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2024-12-06', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D009437', 'term': 'Neuralgia'}], 'ancestors': [{'id': 'D010523', 'term': 'Peripheral Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D010146', 'term': 'Pain'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017294', 'term': 'Ondansetron'}, {'id': 'C402343', 'term': 'tariquidar'}], 'ancestors': [{'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D002227', 'term': 'Carbazoles'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006575', 'term': 'Heterocyclic Compounds, 3-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'sharout@wustl.edu', 'phone': '3132861715', 'title': 'Simon Haroutounian', 'organization': 'Washington University in St Louis'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Due to ethical considerations, cerebrospinal fluid (CSF) sampling was optional in the study, therefore data on plasma/CSF ratio is not available for all patients.\n\nA total of 24 patients were enrolled out of 28 participant planned.'}}, 'adverseEventsModule': {'timeFrame': '6 weeks', 'eventGroups': [{'id': 'EG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.', 'otherNumAtRisk': 23, 'deathsNumAtRisk': 23, 'otherNumAffected': 12, 'seriousNumAtRisk': 23, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.', 'otherNumAtRisk': 24, 'deathsNumAtRisk': 24, 'otherNumAffected': 19, 'seriousNumAtRisk': 24, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 7, 'numAffected': 7}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Metallic Taste', 'notes': 'Dysgeusia (Change in taste)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 8, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Drowsiness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dry Mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Paraesthesia', 'notes': 'specifically facial tingling', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Syncope', 'notes': 'Vasovagal response (syncope) during needle placement', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Infusion site bruising', 'notes': 'Pain/bruising/burning at infusion site', 'stats': [{'groupId': 'EG000', 'numAtRisk': 23, 'numEvents': 8, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 24, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}], 'frequencyThreshold': '4'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Concertation-time Profile of Ondansetron in Plasma, Measured by the Area Under the Concentration-time Curve (AUC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}, {'id': 'OG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.89', 'spread': '0.29', 'groupId': 'OG000'}, {'value': '0.87', 'spread': '0.45', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.8651', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.0204257', 'ciLowerLimit': '-0.2624635', 'ciUpperLimit': '0.2216122', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Measurements over 240 minutes, extrapolated to infinity', 'description': 'AUCinf for Ondansetron concentration in plasma based on venous blood sampling for plasma concentrations of ondansetron obtained at 0, 15, 30, 60, 90, 120, 180, and 240 minutes from the beginning of ondansetron infusion.', 'unitOfMeasure': 'mg*hr/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'participants who completed both sessions'}, {'type': 'PRIMARY', 'title': 'Cerebrospinal Fluid to Plasma Concentration Ratio of Ondansetron', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}, {'id': 'OG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.132', 'spread': '0.017', 'groupId': 'OG000'}, {'value': '0.112', 'spread': '0.018', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.056', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Net)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.01727052', 'ciLowerLimit': '-0.0005895', 'ciUpperLimit': '0.03513063', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'anytime between 0-240 minutes', 'description': 'The level of ondansetron in plasma and CSF (cerebrospinal fluid) in samples, taken around the same time, was measured, and the ratio of the two values was calculated. This ratio (partition coefficient, Kp) of ondansetron, compared between the two sessions, with placebo vs tariquidar', 'unitOfMeasure': 'ratio', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Participant who had both CSF and plasma samples drawn at the same time, at both sessions.'}, {'type': 'SECONDARY', 'title': '% Change in Pain Intensity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}, {'id': 'OG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}], 'classes': [{'categories': [{'measurements': [{'value': '37.2', 'spread': '35.1', 'groupId': 'OG000'}, {'value': '28.8', 'spread': '28.7', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline to 90 minutes after ondansetron IV infusion', 'description': 'Change in spontaneous pain intensity (measured on a 0-10 numerical rating scale; 0=no pain, 10=worst imaginable pain) from baseline to 90 minutes after ondansetron IV infusion, compared between two sessions with and without tariquidar. Values are presented as a percentage change from baseline.', 'unitOfMeasure': '% change from baseline', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients who received both treatments, excluding pharmacokinetic outlier (patient N 06)'}, {'type': 'SECONDARY', 'title': 'Conditioned Pain Modulation (CPM) Magnitude (ΔCPM)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}, {'id': 'OG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.1', 'spread': '8.2', 'groupId': 'OG000'}, {'value': '1.8', 'spread': '10.4', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 90 minutes after the end of ondansetron infusion', 'description': 'Conditioned Pain Modulation (CPM) is a psychophysical test to assess the efficiency of descending pain inhibition. CPM is calculated as difference in heat pain threshold with and without pain conditioning - i.e. immersion of a hand in cold water. Conditioned Pain Modulation (CPM) Negative CPM values represent efficient pain modulation/inhibition.\n\nThis test was administered at baseline, and again 90-min after the end of ondansetron infusion. CPM values can range from -100 to 100, CPM\\<0 (i.e. decreased pain to heat stimulus following conditioning) implies descending pain inhibition.\n\nCPM Magnitude (ΔCPM) is the calculated by subtracting the measurement of CPM at baseline \\[possible range of CPM scores 0-100\\] from the measurement of CPM 90 min after the intervention \\[possible range of CPM scores 0-100\\]. A larger negative ΔCPM value indicates increased pain modulation efficiency following treatment, and therefore, a desired outcome.', 'unitOfMeasure': 'score on a scale of 0-100', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients who completed both CPM procedures'}, {'type': 'SECONDARY', 'title': 'Correlation Between CPM Magnitude (ΔCPM) and Change in Pain Intensity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}, {'id': 'OG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.02', 'groupId': 'OG000'}, {'value': '0.01', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '0-240 min from infusion', 'description': 'The association between baseline Conditioned Pain Modulation (CPM) magnitude (ΔCPM) and the % pain reduction from baseline will be determined by bivariate regression.', 'unitOfMeasure': 'r2', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients who completed CPM and reported spontaneous pain intensity at corresponding time points'}, {'type': 'SECONDARY', 'title': 'Change in Neuropathic Pain Symptom Inventory (NPSI) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ondansetron + Tariquidar', 'description': 'Ondansetron 16 mg with Tariquidar: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}, {'id': 'OG001', 'title': 'Ondansetron + Placebo', 'description': 'Ondansetron 16 mg with Placebo: In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.'}], 'classes': [{'categories': [{'measurements': [{'value': '-8.6', 'spread': '7.0', 'groupId': 'OG000'}, {'value': '-13.2', 'spread': '7.1', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'baseline to 70 min after infusion', 'description': 'Changes in the Neuropathic Pain Symptom Inventory (NPSI) total score will be compared between treatment sessions.\n\nNPSI is a questionnaire used to assess and quantify neuropathic pain by asking patients to rate the severity of different pain sensations on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. The version administered in the study consists of seven questions, each rated on a scale from 0 to 10, with the total score being the sum of all ratings.\n\nThe possible range of the NPSI score of the version administered in the study is 70, and, since we measure the difference in scores, the changes in the NPSI score of the version administered in the study is -70 to 70. Higher NPSI scores indicate more severe neuropathic pain symptoms. Since the analysis is conducted on changes in NPSI scores from baseline, a more negative value corresponds to a greater reduction in neuropathic pain symptoms following treatment.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ondansetron/Placebo First, Then Ondasetron/Tariquidar', 'description': 'The study group where patients received Ondansetron with Placebo during Visit 1, and after a washout period of 3 weeks Ondansetron with Tariquidar at Visit 2 per the randomization schedule.\n\nOndansetron 16 mg was administered IV over 60 minutes with placebo (D5W) or with tariquidar (4mg/kg dose in D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.'}, {'id': 'FG001', 'title': 'Ondansetron/Tariquidar First, Then Ondansetron/Placebo', 'description': 'The study group where patients received Ondansetron with Tariquidar during Visit 1, and after 3 weeks of washout period Ondansetron with Placebo at Visit 2 per the randomization schedule.\n\nOndansetron 16 mg was administered IV over 60 minutes with tariquidar (4mg/kg dose in D5W) or with placebo (D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.'}], 'periods': [{'title': 'Visit 1', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Wash-out (3 Weeks)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Visit 2', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Ondansetron With Tariquidar First, Then Ondansetron With Placebo', 'description': 'The study group where patients received Ondansetron with Tariquidar during Visit 1, and Ondansetron with Placebo at Visit 2 per the randomization schedule. The washout period between two visits was 3 weeks.\n\nOndansetron 16 mg was administered IV over 60 minutes with tariquidar (4mg/kg dose in D5W) or with placebo (D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.'}, {'id': 'BG001', 'title': 'Ondansetron With Placebo First, Then Ondansetron With Tariquidar', 'description': 'The study group where patients received Ondansetron with Placebo during Visit 1, and Ondansetron with Tariquidar at Visit 2 per the randomization schedule. The washout period between two visits was 3 weeks.\n\nOndansetron 16 mg was administered IV over 60 minutes with placebo (D5W) or with tariquidar (4mg/kg dose in D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '52.5', 'spread': '12.87', 'groupId': 'BG000'}, {'value': '49.33', 'spread': '12.16', 'groupId': 'BG001'}, {'value': '50.92', 'spread': '12.35', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', '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': '12', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '24', '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': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', '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': '11', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '23', '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'}], 'populationDescription': 'Data from 24 enrolled patients were used in baseline analysis.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2022-04-21', 'size': 1224232, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2024-11-11T12:30', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Prospective, randomized, double blind, crossover study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-01-31', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2023-11-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-07-28', 'studyFirstSubmitDate': '2020-09-21', 'resultsFirstSubmitDate': '2024-11-11', 'studyFirstSubmitQcDate': '2020-10-22', 'lastUpdatePostDateStruct': {'date': '2025-08-14', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-07-28', 'studyFirstPostDateStruct': {'date': '2020-10-26', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-08-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-10-21', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Concertation-time Profile of Ondansetron in Plasma, Measured by the Area Under the Concentration-time Curve (AUC)', 'timeFrame': 'Measurements over 240 minutes, extrapolated to infinity', 'description': 'AUCinf for Ondansetron concentration in plasma based on venous blood sampling for plasma concentrations of ondansetron obtained at 0, 15, 30, 60, 90, 120, 180, and 240 minutes from the beginning of ondansetron infusion.'}, {'measure': 'Cerebrospinal Fluid to Plasma Concentration Ratio of Ondansetron', 'timeFrame': 'anytime between 0-240 minutes', 'description': 'The level of ondansetron in plasma and CSF (cerebrospinal fluid) in samples, taken around the same time, was measured, and the ratio of the two values was calculated. This ratio (partition coefficient, Kp) of ondansetron, compared between the two sessions, with placebo vs tariquidar'}], 'secondaryOutcomes': [{'measure': '% Change in Pain Intensity', 'timeFrame': 'baseline to 90 minutes after ondansetron IV infusion', 'description': 'Change in spontaneous pain intensity (measured on a 0-10 numerical rating scale; 0=no pain, 10=worst imaginable pain) from baseline to 90 minutes after ondansetron IV infusion, compared between two sessions with and without tariquidar. Values are presented as a percentage change from baseline.'}, {'measure': 'Conditioned Pain Modulation (CPM) Magnitude (ΔCPM)', 'timeFrame': 'Baseline and 90 minutes after the end of ondansetron infusion', 'description': 'Conditioned Pain Modulation (CPM) is a psychophysical test to assess the efficiency of descending pain inhibition. CPM is calculated as difference in heat pain threshold with and without pain conditioning - i.e. immersion of a hand in cold water. Conditioned Pain Modulation (CPM) Negative CPM values represent efficient pain modulation/inhibition.\n\nThis test was administered at baseline, and again 90-min after the end of ondansetron infusion. CPM values can range from -100 to 100, CPM\\<0 (i.e. decreased pain to heat stimulus following conditioning) implies descending pain inhibition.\n\nCPM Magnitude (ΔCPM) is the calculated by subtracting the measurement of CPM at baseline \\[possible range of CPM scores 0-100\\] from the measurement of CPM 90 min after the intervention \\[possible range of CPM scores 0-100\\]. A larger negative ΔCPM value indicates increased pain modulation efficiency following treatment, and therefore, a desired outcome.'}, {'measure': 'Correlation Between CPM Magnitude (ΔCPM) and Change in Pain Intensity', 'timeFrame': '0-240 min from infusion', 'description': 'The association between baseline Conditioned Pain Modulation (CPM) magnitude (ΔCPM) and the % pain reduction from baseline will be determined by bivariate regression.'}, {'measure': 'Change in Neuropathic Pain Symptom Inventory (NPSI) Score', 'timeFrame': 'baseline to 70 min after infusion', 'description': 'Changes in the Neuropathic Pain Symptom Inventory (NPSI) total score will be compared between treatment sessions.\n\nNPSI is a questionnaire used to assess and quantify neuropathic pain by asking patients to rate the severity of different pain sensations on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. The version administered in the study consists of seven questions, each rated on a scale from 0 to 10, with the total score being the sum of all ratings.\n\nThe possible range of the NPSI score of the version administered in the study is 70, and, since we measure the difference in scores, the changes in the NPSI score of the version administered in the study is -70 to 70. Higher NPSI scores indicate more severe neuropathic pain symptoms. Since the analysis is conducted on changes in NPSI scores from baseline, a more negative value corresponds to a greater reduction in neuropathic pain symptoms following treatment.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Neuropathic Pain']}, 'referencesModule': {'references': [{'pmid': '27115670', 'type': 'BACKGROUND', 'citation': 'Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.'}, {'pmid': '20849570', 'type': 'BACKGROUND', 'citation': 'Yawn BP, Wollan PC, Weingarten TN, Watson JC, Hooten WM, Melton LJ 3rd. The prevalence of neuropathic pain: clinical evaluation compared with screening tools in a community population. Pain Med. 2009 Apr;10(3):586-93. doi: 10.1111/j.1526-4637.2009.00588.x. Epub 2009 Mar 17.'}, {'pmid': '22395856', 'type': 'BACKGROUND', 'citation': 'Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep. 2012 Jun;16(3):191-8. doi: 10.1007/s11916-012-0256-0.'}]}, 'descriptionModule': {'briefSummary': 'Prospective, randomized, double-blind, placebo controlled, cross-over proof of concept study.\n\nTo determine the pharmacokinetics and tolerability of co-administration of 5-HT3R antagonist ondansetron with a P-glycoprotein inhibitor tariquidar, in patients with neuropathic pain.', 'detailedDescription': 'The investigators hypothesize that co-administration of a 5-HT3 receptor antagonist ondansetron (single 16mg dose) with p-glycoprotein inhibitor tariquidar (single 4mg/kg dose) vs placebo in a cross-over prospective randomized study, will:\n\n1. Be tolerable in patients with neuropathic pain.\n2. Increase the cerebrospinal fluid (CSF) to plasma ratio of ondansetron after intravenous administration, compare to ondansetron alone\n3. Result in a greater reduction in pain intensity than with ondansetron alone.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Age 18-65;\n2. Documented diagnosis of neuropathic pain due to damage or disease affecting the peripheral nervous system;\n3. At least Probable neuropathic pain grading1;\n4. Pain duration \\>3 months;\n5. Average pain intensity ≥4 on 0-10 numerical rating scale (NRS).\n\nExclusion Criteria:\n\n1. Current pregnancy or lactation;\n2. Moderate-severe kidney or liver dysfunction;\n3. Active cardiac arrhythmias (non-sinus rhythm), Long QT syndrome, or QTc interval \\>450msec;\n4. Congestive heart failure\n5. Abnormal troponin values at screening visit;\n6. Current treatment with MAO inhibitors, mirtazapine, SSRI antidepressants, or SNRI medications duloxetine or venlafaxine;\n7. Current treatment with tapentadol, tramadol, or fentanyl;\n8. Current treatment with P-glycoprotein substrate drugs with narrow therapeutic window, e.g. digoxin;\n9. Current treatment with tricyclic antidepressant medications (e.g. amitriptyline, desipramine, imipramine) at a dose \\>25mg/day;\n10. Ongoing use of any of the following medications with known effects on Pgp function: carbamazepine, phenytoin, phenobarbital, cyclosporine, clarithromycin, erythromycin, ritonavir, verapamil, rifampicin, St. John's wort;\n11. Current treatment with QT-prolonging drugs, and drugs known to have a significant interaction with ondansetron or other P-glycoprotein substrates (see section 2.3.3.);\n12. Current treatment with anticoagulant drugs;"}, 'identificationModule': {'nctId': 'NCT04603066', 'briefTitle': 'Tariquidar-ondansetron Combination in Neuropathic Pain', 'organization': {'class': 'OTHER', 'fullName': 'Washington University School of Medicine'}, 'officialTitle': 'Administration of Ondansetron With P-glycoprotein Inhibitor Tariquidar in Patients With Neuropathic Pain', 'orgStudyIdInfo': {'id': '202008183'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Ondansetron/Placebo first, then Ondansetron/Tariquidar', 'description': 'The study group where patients received Ondansetron with Placebo during Visit 1, and after a washout period of 3 weeks Ondansetron with Tariquidar at Visit 2 per the randomization schedule.\n\nOndansetron 16 mg was administered IV over 60 minutes with placebo (D5W) or with tariquidar (4mg/kg dose in D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.', 'interventionNames': ['Drug: Ondansetron 16 mg with Tariquidar', 'Drug: Ondansetron 16 mg with Placebo']}, {'type': 'OTHER', 'label': 'Ondansetron/Tariquidar first, then Ondansetron/Placebo', 'description': 'The study group where patients received Ondansetron with Tariquidar during Visit 1, and after 3 weeks of washout period Ondansetron with Placebo at Visit 2 per the randomization schedule.\n\nOndansetron 16 mg was administered IV over 60 minutes with tariquidar (4mg/kg dose in D5W) or with placebo (D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.', 'interventionNames': ['Drug: Ondansetron 16 mg with Tariquidar', 'Drug: Ondansetron 16 mg with Placebo']}], 'interventions': [{'name': 'Ondansetron 16 mg with Tariquidar', 'type': 'DRUG', 'otherNames': ['Ondansetron/Tariquidar'], 'description': 'In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.', 'armGroupLabels': ['Ondansetron/Placebo first, then Ondansetron/Tariquidar', 'Ondansetron/Tariquidar first, then Ondansetron/Placebo']}, {'name': 'Ondansetron 16 mg with Placebo', 'type': 'DRUG', 'otherNames': ['Ondansetron/ Placebo'], 'description': 'In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.', 'armGroupLabels': ['Ondansetron/Placebo first, then Ondansetron/Tariquidar', 'Ondansetron/Tariquidar first, then Ondansetron/Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University School of Medicine/Barnes-Jewish Hospital', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}], 'overallOfficials': [{'name': 'Simon Haroutounian, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Washington University School of Medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Washington University School of Medicine', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'simon.haroutounian', 'investigatorAffiliation': 'Washington University School of Medicine'}}}}