Ignite Creation Date:
2024-05-06 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 12:40 PM
Study NCT ID:
NCT03435146
Status:
COMPLETED
Last Update Posted:
2023-02-02
First Post:
2017-08-21
Brief Title:
Safety Tolerability DDI Short Course Treatment of LTBI Infection With High-dose Rifapentine and Isoniazid or Standard Isoniazid Preventive Therapy in HIV Patients DOLPHIN DOLPHIN TOO
Sponsor:
The Aurum Institute NPC
Organization:
The Aurum Institute NPC
Study Overview
Official Title:
Safety Tolerability and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Rifapentine and Isoniazid or Standard Isoniazid Preventative Therapy Among HIV-infected Patients Taking Dolutegravir-based Antiretroviral Treatment
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMPAACT4TB
Brief Summary:
Single-arm single-center Phase III clinical trial in four groups Individuals with HIV infection taking Efavirenz EFV and two nucleoside reverse transcriptase inhibitors NRTI who have undetectable Groups 1 and 2 or detectable Group 3 and 4 HIV viral load and an indication for TPT will be switched to DTG with tenofoviremtricitabine Groups 1 and 2 or lamivudinetenofovir Groups 3 and 4 Group 1 and 2 will receive weekly HP for 12 total doses starting 8 weeks after initiating DTG Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least eight weeks and have not received efavirenz or nevirapine for at least two months who have an undetectable HIV viral load may also participate Individuals with HIV infection who are ART treatment naïve at any HIV viral load level and have an indication for TPT will start DTG and be enrolled to receive standard IPT Group 3 or HP Group 4 initiated at the same time as DTG Group 3 and 4 will be enrolled after follow up of Group 1 and 2 has been completed
Detailed Description:
Group 1 n30 The first 12 participants Group 1A will take dolutegravir 50 milligrams mg once daily with tenofoviremtricitabine from Days 1-57 Semi-intensive PK sampling for dolutegravir will be performed on Day 57 Participants will continue once-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 58 Semi-intensive PK sampling for dolutegravir will be performed on Day 72 with the 3rd dose of HP and Day 108 following the 8th dose of HP Trough concentrations CT will be measured on Days 59 74 and 78 PK assessments will be performed at weeks 9 and 11 for rifapentine and at week 11 for isoniazid VL will be measured at baseline and weeks 11 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline and weeks 9 11 13 16 20 and 24
After the 12 Group 1A participants have completed the second semi-intensive PK visit an interim PK safety and VL assessment will be performed to ensure that the 50 mg once daily dose is safe and meets PK targets The subsequent 18 participants in Group 1 Group 1B will receive either dolutegravir 50 mg or a higher dose of dolutegravir if dose adjustment is required eg dolutegravir 50 mg twice daily just on HP dosing days dolutegravir 50 mg twice daily seven days a week etc A second interim evaluation focused on PK will occur after all Group 1B participants have completed the Week 11 semi-intensive PK visit This evaluation will include all PK data from Group 1A who will have completed their Week 16 semi-intensive PK visit plus PK data from Group 1B up to and including the Week 11 semi-intensive PK visit
A third interim evaluation focused on safety and virologic response will occur after all participants Groups 1A 1B and 2 have completed the Week 11 visit This evaluation will include all safety data and HIV viral load information collected up until that point from all participants
Group 2 n30 These participants will receive dolutegravir and HP at the same doses and dose schedule as the participants in Group 1B They will undergo safety assessments at baseline and weeks 9 11 13 16 20 and 24 HIV VL assessments will be performed at baseline and weeks 11 and 24 Sparse trough PK samples for dolutegravir will be collected on two occasions
Group 3 n25 The next 25 participants who are ART treatment naïve will start dolutegravir 50 milligrams mg once daily with tenofovirlamivudine on study Day 0 Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 1 24 hours after taking the first dose of DTG and before taking the first dose of standard isoniazid Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 24 Week 3 to parallel 721 hours after the 3rd dose of HP The final sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 59 Week 8 to parallel 721 hours after the 8th dose of HP HIV VL will be measured at screening and Weeks 3 8 12 16 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline Creatinine will be repeated at Weeks 2 4 8 12 16 and 24 and LFTs will be repeated at weeks 4 8 and 12
Group 4 n50 After Group 3 is fully enrolled another group of 50 participants who are ART treatment naïve will start dolutegravir 50 milligrams mg once daily with tenofovirlamivudine on Day 0 They will begin TPT with once weekly HP the day after starting DTG on Day 1 Sparse PK sampling for trough concentrations CT dolutegravir will be performed on Day 1 24 hours after the first dose of DTG before the first dose of HP Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 24 721 hours after the third dose of HP Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 59 721 hours after the eighth dose of HP HIV VL will be measured at screening and Weeks 3 8 12 16 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline Creatinine will be repeated at Weeks 2 4 8 12 16 and 24 and LFTs will be repeated at weeks 4 8 and 12
1 - 24 hours
After the 12 Group 1A participants have completed the second semi-intensive PK visit an interim PK safety and VL assessment will be performed to ensure that the 50 mg once daily dose is safe and meets PK targets The subsequent 18 participants in Group 1 Group 1B will receive either dolutegravir 50 mg or a higher dose of dolutegravir if dose adjustment is required eg dolutegravir 50 mg twice daily just on HP dosing days dolutegravir 50 mg twice daily seven days a week etc A second interim evaluation focused on PK will occur after all Group 1B participants have completed the Week 11 semi-intensive PK visit This evaluation will include all PK data from Group 1A who will have completed their Week 16 semi-intensive PK visit plus PK data from Group 1B up to and including the Week 11 semi-intensive PK visit
A third interim evaluation focused on safety and virologic response will occur after all participants Groups 1A 1B and 2 have completed the Week 11 visit This evaluation will include all safety data and HIV viral load information collected up until that point from all participants
Group 2 n30 These participants will receive dolutegravir and HP at the same doses and dose schedule as the participants in Group 1B They will undergo safety assessments at baseline and weeks 9 11 13 16 20 and 24 HIV VL assessments will be performed at baseline and weeks 11 and 24 Sparse trough PK samples for dolutegravir will be collected on two occasions
Group 3 n25 The next 25 participants who are ART treatment naïve will start dolutegravir 50 milligrams mg once daily with tenofovirlamivudine on study Day 0 Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 1 24 hours after taking the first dose of DTG and before taking the first dose of standard isoniazid Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 24 Week 3 to parallel 721 hours after the 3rd dose of HP The final sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 59 Week 8 to parallel 721 hours after the 8th dose of HP HIV VL will be measured at screening and Weeks 3 8 12 16 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline Creatinine will be repeated at Weeks 2 4 8 12 16 and 24 and LFTs will be repeated at weeks 4 8 and 12
Group 4 n50 After Group 3 is fully enrolled another group of 50 participants who are ART treatment naïve will start dolutegravir 50 milligrams mg once daily with tenofovirlamivudine on Day 0 They will begin TPT with once weekly HP the day after starting DTG on Day 1 Sparse PK sampling for trough concentrations CT dolutegravir will be performed on Day 1 24 hours after the first dose of DTG before the first dose of HP Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 24 721 hours after the third dose of HP Sparse PK sampling for trough concentrations CT of dolutegravir will be performed on Day 59 721 hours after the eighth dose of HP HIV VL will be measured at screening and Weeks 3 8 12 16 and 24 Safety labs complete blood count CBC urea and electrolytes UE and creatinine and liver function tests LFT will be obtained at baseline Creatinine will be repeated at Weeks 2 4 8 12 16 and 24 and LFTs will be repeated at weeks 4 8 and 12
1 - 24 hours
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None