Ignite Creation Date:
2025-12-24 @ 2:28 PM
Ignite Modification Date:
2026-01-03 @ 7:59 PM
Study NCT ID:
NCT03731559
Status:
RECRUITING
Last Update Posted:
2024-10-02
First Post:
2018-10-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Efficacy, Safety and Pharmacokinetics of DTG with RIF
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C562325', 'term': 'dolutegravir'}, {'id': 'D005502', 'term': 'Food'}, {'id': 'C494814', 'term': 'BID protein, human'}], 'ancestors': [{'id': 'D000066888', 'term': 'Diet, Food, and Nutrition'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}, {'id': 'D019602', 'term': 'Food and Beverages'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-06-25', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-09', 'completionDateStruct': {'date': '2025-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-09-30', 'studyFirstSubmitDate': '2018-10-31', 'studyFirstSubmitQcDate': '2018-11-02', 'lastUpdatePostDateStruct': {'date': '2024-10-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-11-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-06-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'proportion of subjects from the ITT analysis population with plasma HIV-1 RNA <50 c/mL at Week 24', 'timeFrame': 'Week 24', 'description': 'The primary efficacy endpoint is the proportion of subjects from the ITT analysis population with plasma HIV-1 RNA \\<50 c/mL at Week 24.'}], 'secondaryOutcomes': [{'measure': 'AUC of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID', 'timeFrame': 'Week 4', 'description': 'AUC of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID'}, {'measure': 'Cmax of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID', 'timeFrame': 'Week 4', 'description': 'Cmax of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID'}, {'measure': 'Cmin of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID', 'timeFrame': 'Week 4', 'description': 'Cmin of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID'}, {'measure': 'Oral clearance of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID', 'timeFrame': 'Week 4', 'description': 'Oral clearance of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID'}, {'measure': 'Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24', 'timeFrame': 'Week 24', 'description': 'Proportion of subjects with plasma HIV-1 RNA \\<50 c/mL at Week 24'}, {'measure': 'Changes in CD4+ counts from baseline to Week 24 and Week 48', 'timeFrame': 'Weeks 24 and 48', 'description': 'Changes in CD4+ counts from baseline to Week 24 and Week 48'}, {'measure': 'Incidence of disease progression', 'timeFrame': 'Week 48', 'description': 'Incidence of disease progression (HIV-associated conditions, new AIDS diagnoses, and death)'}, {'measure': 'Proportion of subjects that have completed TB treatment', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects that have completed TB treatment'}, {'measure': 'Proportion of subjects that are cured from TB', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects that are cured from TB'}, {'measure': 'Proportion of subjects that have relapsed', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects that have relapsed'}, {'measure': 'Proportion of subjects that have defaulted', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects that have defaulted'}, {'measure': 'TB outcome in terms of cure', 'timeFrame': 'Week 48', 'description': 'Number of participants that have been cured of TB'}, {'measure': 'TB outcome in terms of relapse', 'timeFrame': 'Week 48', 'description': 'Number of participants with relapse'}, {'measure': 'TB outcome in terms of treatment failure due to TB resistance', 'timeFrame': 'Week 48', 'description': 'Number of participants with treatment failure due to TB resistance'}, {'measure': 'TB outcome in terms of incidence', 'timeFrame': 'Week 48', 'description': 'Incidence of all AEs, SAEs, and laboratory abnormalities'}, {'measure': 'TB outcome in terms of severity', 'timeFrame': 'Week 48', 'description': 'Severity of all AEs, SAEs, and laboratory abnormalities'}, {'measure': 'discontinuation from the study', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects who permanently discontinued randomization arm due to AEs or death'}, {'measure': 'discontinuation from the study drugs', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects who temporarily discontinued the study drugs and/or TB therapy due to AEs'}, {'measure': 'Proportion of subjects with TB-associated IRIS', 'timeFrame': 'Week 48', 'description': 'Proportion of subjects with TB-associated IRIS'}, {'measure': 'AUC of DTG at Weeks 4 (with RIF) and 48 (without RIF)', 'timeFrame': 'Weeks 4 and 48', 'description': 'AUC of DTG at Weeks 4 (with RIF) and 48 (without RIF) will be analyzed using population PK modeling approach to estimate AUC'}, {'measure': 'Cmax of DTG at Weeks 4 (with RIF) and 48 (without RIF)', 'timeFrame': 'Weeks 4 and 48', 'description': 'Cmax of DTG at Weeks 4 (with RIF) and 48 (without RIF) will be analyzed using population PK modeling approach to estimate Cmax'}, {'measure': 'Ctrough of DTG at Weeks 4 (with RIF) and 48 (without RIF)', 'timeFrame': 'Weeks 4 and 48', 'description': 'Ctrough of DTG at Weeks 4 (with RIF) and 48 (without RIF) will be analyzed using population PK modeling approach to estimate Ctrough'}, {'measure': 'proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48', 'timeFrame': 'Week 48', 'description': 'proportion of subjects with plasma HIV-1 RNA \\<50 c/mL at Week 48 (viral suppression)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Efficacy', 'safety', 'pharmacokinetics', 'Dolutegravir', 'HIV/TB co-infected patients', 'rifampin-based antituberculosis therapy'], 'conditions': ['HIV/TB Coinfection']}, 'descriptionModule': {'briefSummary': 'The overall aim of the project is to evaluate optimal DTG dose for the combined treatment of TB and HIV infections with RIF based anti-TB therapy. This Stage II trial will determine precisely the PK parameters of DTG in combination with RIF regimen in Thai HIV/TB co-infected patients. After the optimal dose of DTG has been found, it will be further tested in a larger Stage III trial to assess its safety, tolerability and efficacy when used with RIF based regimen.', 'detailedDescription': 'This is a Stage II, randomized, open-label study describing the efficacy and safety of DTG 50 mg OD with food and DTG 50 mg BID plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy. The study will be conducted in approximately 200 HIV-1 infected individuals who are ART-naïve and newly diagnosed with probable or confirmed pulmonary, pleural, or lymph node (LN) Mycobacterium TB (MTB) taking RIF-containing first-line TB treatment. Subjects should have confirmed RIF-sensitive MTB infection as determined by GeneXpert (or equivalent approved molecular test) or mycobacterial culture.\n\nThe study is comprised two different stages:\n\n1. Stage1, investigators will test the safety and tolerability, as well as Pharmacokinetics (PK), of two different doses of dolutegravir co-administered with standard anti-TB treatment. Overall, 40 HIV/TB patients will be enrolled. They will be randomized to 2 groups (DTG 50 mg with food and DTG 50 mg BID). Intensive PK of DTG will be performed at week 4. Interim analysis will be performed if all 40 cases completed 12 weeks and 24 weeks. Premature study termination will be set for\n\n 1. proportion of HIV RNA \\< 50 copies/ml at week 24 between 2 group is different \\> 20%\n 2. DTG 50 mg with food has geometric mean DTG Ctrough \\< 0.3 mg/L If there is no premature study termination met, the study will move to stage 2. Stage 2 will only be recruited if two different doses of dolutegravir are well tolerated and safe.\n2. Stage 2: 160 HIV/TB patients will be enrolled. They will be randomized to 2 groups (DTG 50 mg with food and DTG 50 mg BID). DTG concentration will be performed at week 4 and 48. Interim analysis will be performed if all 200 cases completed 24 weeks.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. documented HIV positive\n2. Aged \\>18 years\n3. ARV naïve (previous exposure to ARV for \\< 2 weeks)\n4. Any CD4 cell count\n5. ALT \\<5 times ULN\n6. estimated GFR\\>60 ml/min/1.73m2\n7. Hemoglobin \\>7 mg/L\n8. TB is diagnosed and there is a plan to receive stable doses of RIF containing anti-TB therapy for at least another 4 week period after initiation of ART\n9. No other active OI (CDC class C event) except oral candidiasis or disseminated MAC\n10. Body weight \\>40kg\n11. Able to provide written informed consent\n\nExclusion Criteria:\n\n1. Have documented history of HIV treatment failure or HIV mutation to NRTI, NNRTI, and/or INIs\n2. Have previously treated for tuberculosis\n3. Currently using immunosuppressive agents.\n4. Currently using any prohibited medications that can affect the pharmacokinetics of the study drug such as phenobarbital, and carbamazepine\n5. Currently using alcohol or illicit substances that may affect the conduct of the trial as per the opinion of the site Principal Investigator\n6. Unlikely to be able to remain in the follow-up period as defined by the protocol\n7. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST \\< 5 x ULN.\n8. Have Karnofsky performance score \\<30%\n9. Have TB meningitis, bone/joints (due to prolonged use of anti-TB drug)\n10. Pregnant or breastfeeding'}, 'identificationModule': {'nctId': 'NCT03731559', 'briefTitle': 'Efficacy, Safety and Pharmacokinetics of DTG with RIF', 'organization': {'class': 'OTHER', 'fullName': 'The HIV Netherlands Australia Thailand Research Collaboration'}, 'officialTitle': 'Efficacy, Safety and Pharmacokinetics of Dolutegravir 50 Mg Once Daily with Food Versus Dolutegravir 50 Mg Twice Daily in HIV/TB Co-infected Patients Receiving Rifampin-based Antituberculosis Therapy', 'orgStudyIdInfo': {'id': 'HIV-NAT 254'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'DTG 50 mg OD with food', 'description': 'DTG 50 mg OD with food plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy.', 'interventionNames': ['Drug: DTG 50 mg OD with food']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'DTG 50 mg BID', 'description': 'DTG 50 mg BID plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy.', 'interventionNames': ['Drug: DTG 50 mg BID']}], 'interventions': [{'name': 'DTG 50 mg OD with food', 'type': 'DRUG', 'description': 'Dolutegravir 50 mg once daily with food plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy', 'armGroupLabels': ['DTG 50 mg OD with food']}, {'name': 'DTG 50 mg BID', 'type': 'DRUG', 'description': 'Dolutegravir 50 mg BID plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy.', 'armGroupLabels': ['DTG 50 mg BID']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10100', 'city': 'Bangkok', 'state': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Praniti Danpornprasert, MD', 'role': 'CONTACT'}], 'facility': 'Klang Hospital', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}, {'zip': '10220', 'city': 'Bangkok', 'state': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Chris Fujitnirun, MD', 'role': 'CONTACT', 'email': 'fujitnirunchris@gmail.com'}, {'name': 'Chris Fujitnirun, MD', 'role': 'CONTACT'}], 'facility': 'Bhumibol Adulyadej Hospital', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}, {'zip': '10330', 'city': 'Bangkok', 'state': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Gompol Suwanpimolkul, MD', 'role': 'CONTACT', 'email': 'sgompol@gmail.com'}, {'name': 'Gompol Suwanpimolkul', 'role': 'CONTACT'}, {'name': 'Opass Putcharoen', 'role': 'CONTACT'}], 'facility': 'Infectious Disease, Chulalongkorn University', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}, {'zip': '10600', 'city': 'Bangkok', 'state': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Supannee Jirajariyavet, MD', 'role': 'CONTACT', 'email': 'jsupunee@yahoo.com'}, {'name': 'Supannee Jirajariyavet, MD', 'role': 'CONTACT'}], 'facility': 'Infectious Disease Taksin Hospital', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}, {'zip': '20000', 'city': 'Chon Buri', 'state': 'Changwat Chon Buri', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Palakorn Panarat, MD', 'role': 'CONTACT'}], 'facility': 'Infectious Disease Chonburi Hospital', 'geoPoint': {'lat': 13.3622, 'lon': 100.98345}}, {'zip': '11000', 'city': 'Nonthaburi', 'state': 'Changwat Nonthaburi', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Weerawat Manosuthi, MD', 'role': 'CONTACT', 'email': 'drweerawat@hotmail.com'}, {'name': 'Weerawat Manosuthi, MD', 'role': 'CONTACT'}], 'facility': 'Bamrasnaradura Infectious Diseases Institute', 'geoPoint': {'lat': 13.86075, 'lon': 100.51477}}, {'zip': '65000', 'city': 'Phitsanulok', 'state': 'Changwat Phitsanulok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Pornpit Treebupachatsakul, MD', 'role': 'CONTACT'}], 'facility': 'Infectious Disease Buddhachinaraj Phitsanulok Hospital', 'geoPoint': {'lat': 16.82481, 'lon': 100.25858}}, {'zip': '57000', 'city': 'Chiang Rai', 'state': 'Chiangrai', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Suwimol Khusuwan, MD', 'role': 'CONTACT'}], 'facility': 'Infectious Disease Chiangrai Prachanukroh Hospital', 'geoPoint': {'lat': 19.90858, 'lon': 99.8325}}, {'zip': '10330', 'city': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Kamol Kawkitinarong, MD', 'role': 'CONTACT', 'email': 'kamonkaw@hotmail.com'}, {'name': 'Kamol Kawkitinarong, MD', 'role': 'CONTACT'}], 'facility': 'Chest Division, Faculty of Medicine, Chulalongkorn University', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}, {'zip': '10330', 'city': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Anchalee Avihingsanon, MD, PhD', 'role': 'CONTACT', 'email': 'anchalee.a@hivnat.org', 'phone': '662 652 3040'}, {'name': 'Anchalee Avihingsanon, MD, PhD', 'role': 'CONTACT'}, {'name': 'Sivaporn Gatechompol, MD', 'role': 'CONTACT'}, {'name': 'Win Min Han, MD', 'role': 'CONTACT'}, {'name': 'Akarin Hiransuthikul, MD', 'role': 'CONTACT'}], 'facility': 'HIV-NAT, Thai Red Cross - AIDS Research Centre', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}], 'centralContacts': [{'name': 'June Ohata, BS', 'role': 'CONTACT', 'email': 'juneohata4@gmail.com', 'phone': '6626523040', 'phoneExt': '147'}], 'overallOfficials': [{'name': 'Anchalee Avihingsanon, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'HIV-NAT, Thai Red Cross - AIDS Research Centre'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The HIV Netherlands Australia Thailand Research Collaboration', 'class': 'OTHER'}, 'collaborators': [{'name': 'Chest Division, Chulalongkorn University', 'class': 'UNKNOWN'}, {'name': 'Infectious Disease, Chulalongkorn University', 'class': 'UNKNOWN'}, {'name': 'Bamrasnaradura Infectious Diseases Institute', 'class': 'OTHER_GOV'}, {'name': 'Bhumibol Adulyadej Hospital', 'class': 'OTHER'}, {'name': 'Infectious Disease Taksin Hospital', 'class': 'UNKNOWN'}, {'name': 'Klang Hospital', 'class': 'UNKNOWN'}, {'name': 'Infectious Disease Chiangrai Prachanukroh Hospital', 'class': 'UNKNOWN'}, {'name': 'Infectious Disease Chonburi Hospital', 'class': 'UNKNOWN'}, {'name': 'Infectious Disease Buddhachinaraj Phitsanulok Hospital', 'class': 'UNKNOWN'}, {'name': 'Radboud University Medical Center', 'class': 'OTHER'}, {'name': 'Ministry of Health, Thailand', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'SPONSOR'}}}}