Trial Outcomes & Findings for Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals (NCT NCT04272242)
NCT ID: NCT04272242
Last Updated: 2024-09-19
Results Overview
This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmax defines the model-predicted maximum concentration observed over the 12- or 24- hours of the DTG dosing interval.
TERMINATED
PHASE2
37 participants
Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28
2024-09-19
Participant Flow
Participants in Arm 1 were enrolled from February 2021 to November 2021 at 9 selected US and non-US ACTG clinical research sites. It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2. Results are for Arm 1 only.
Participants were not randomized and enrollment was not stratified. To create by-country diversity of participants, screening and accrual limits were set for US and non-US sites.
Participant milestones
| Measure |
Arm 1: DTG + INH + RPT
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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Overall Study
STARTED
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37
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Overall Study
COMPLETED
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32
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Arm 1: DTG + INH + RPT
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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Overall Study
Withdrawal by Subject
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3
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Overall Study
Lost to Follow-up
|
1
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Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals
Baseline characteristics by cohort
| Measure |
Arm 1: DTG + INH + RPT
n=37 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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Age, Continuous
|
41.0 years
n=5 Participants
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|
Sex: Female, Male
Female
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14 Participants
n=5 Participants
|
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Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
Haiti
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3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
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4 Participants
n=5 Participants
|
|
Region of Enrollment
Malawi
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4 Participants
n=5 Participants
|
|
Region of Enrollment
Botswana
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3 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Zimbabwe
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
8 Participants
n=5 Participants
|
|
HIV-1 RNA below 50 copies/mL
Below 50 copies/mL
|
36 Participants
n=5 Participants
|
|
HIV-1 RNA below 50 copies/mL
50 copies/mL or Greater
|
1 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28Population: All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28.
This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmax defines the model-predicted maximum concentration observed over the 12- or 24- hours of the DTG dosing interval.
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=32 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day
Day 0
|
4180.8 ng/mL
Interval 3920.6 to 5196.4
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DTG PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day
Day 28
|
3913.5 ng/mL
Interval 3475.7 to 4743.1
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PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28Population: All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28.
This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model. For Arm 1, Day 28 (BID dosing), participant-specific AUC0-24h was estimated by summing participant-specific estimated AUC values for the 0-12 hour dosing interval (AUC0-12).
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=32 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 1 by Visit Day
Day 0
|
68079.5 h*ng/mL
Interval 59139.5 to 85561.0
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DTG PK Parameter Area Under the Concentration Time Curve (AUC0-24) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arm 1 by Visit Day
Day 28
|
65261.3 h*ng/mL
Interval 56748.6 to 81999.4
|
PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at days 0 and 28Population: All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28.
This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 1 at day 0 (DTG QD) and day 28 (DTG BID with 1HP). Cmin defines the model-predicted minimum concentration observed over the 12- or 24- hour DTG dosing interval.
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=32 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day
Day 0
|
1726.1 ng/mL
Interval 1267.9 to 2395.6
|
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DTG PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on DTG Levels From Individual Participants in Arm 1 by Visit Day
Day 28
|
1717.5 ng/mL
Interval 1206.6 to 2502.7
|
PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 13h, 14h, 23h and 24h post-dose at day 28Population: All Arm 1 participants who initiated the 1HP TB regimen, who completed 28 daily doses RPT/INH within the 6-week study period, and who took DTG twice-daily for days 1-28. Sampling took place after ensuring 3 days of consecutive DTG QD dosing prior to day 0, and 3 days of consecutive DTG BID with 1HP dosing prior to Day 28.
This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 1 at day 28 (DTG BID with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 12- hour DTG dosing interval.
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=32 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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DTG PK Parameter Ctrough Determined Based on DTG Levels From Individual Participants in Arm 1 at Day 28
|
1987.0 ng/mL
Interval 1331.0 to 2377.5
|
PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28Population: It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2.
This evaluates the effect of RPT on the DTG PK parameter Cmax obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). Cmax defines the model-predicted maximum concentration observed over the 24- hours of the DTG dosing interval.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28Population: It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2.
This evaluates the effect of RPT on the DTG PK parameter AUC 0-24h obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). AUC 0-24h defines area under the concentration-time curve over the period of 24 hours post-dose estimated based on the fitted model.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28Population: It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2.
This evaluates the effect of RPT on the DTG PK parameter Cmin obtained from participants enrolled in Arm 2 at day 0 (DTG QD) and day 28 (DTG QD with 1HP). Cmin defines the model-predicted minimum concentration observed over the 24- hour DTG dosing interval.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Intensive DTG PK samples at pre-dose, 1h, 2h, 4h, 8h, 12h, 23h and 24h post-dose at days 0 and 28Population: It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2.
This evaluates the effect of RPT on the DTG PK parameter Ctrough obtained from participants enrolled in Arm 2 at day 28 (DTG QD with 1HP). Ctrough defines the observed non-model based minimum concentration observed over the 24- hour DTG dosing interval.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From initiation of study treatment to day 28Population: Participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG.
Arm 1 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants were counted once at the highest grade.
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=36 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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Percentage of Participants in Arm 1 With an Occurrence of Grade 2 or Higher Adverse Event
Grade 2 Adverse Event
|
36 Percentage of participants
Interval 21.0 to 54.0
|
|
Percentage of Participants in Arm 1 With an Occurrence of Grade 2 or Higher Adverse Event
Grade 3 Adverse Event
|
6 Percentage of participants
Interval 1.0 to 19.0
|
SECONDARY outcome
Timeframe: From initiation of study to day 28Population: Participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG.
Percentage of participants in Arm 1 who completed the study
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=36 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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Percentage of Participants in Arm 1 Who Completed the Study
|
89 Percentage of participants
Interval 74.0 to 97.0
|
SECONDARY outcome
Timeframe: From initiation of study treatment to day 28Population: Participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG.
Percentage of participants in Arm 1 who completed study drug treatment (DTG+1HP)
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=36 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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Percentage of Participants in Arm 1 Who Completed Study Drug Treatment
|
92 Percentage of participants
Interval 78.0 to 98.0
|
SECONDARY outcome
Timeframe: Measured at Days 28 and 42Population: All participants in who took at least one dose of study drugs and who had HIV-1 RNA data available.
This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels \>50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment).
Outcome measures
| Measure |
Arm 1: DTG + INH + RPT
n=33 Participants
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
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|---|---|
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Percentage of Participants in Arm 1 With HIV-1 RNA Levels >50 Copies/mL
Percentage with HIV-1 RNA >50 copies/mL at day 28
|
3 percentage of participants
|
|
Percentage of Participants in Arm 1 With HIV-1 RNA Levels >50 Copies/mL
Percentage with HIV-1 RNA >50 copies/mL at day 42
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From initiation of study treatment to day 28Population: It was decided to not move forward with Arm 2 of the study and no participants were enrolled in Arm 2.
Arm 2 participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 2 or higher on a scale of 1 to 5 where 5 is the most severe. Severity graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Participants will be counted once at the highest grade.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From initiation of study to day 28Population: It was decided to not move forward with Arm2 of the study and no participants were enrolled in Arm 2.
Percentage of participants in Arm 2 who completed the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From initiation of study treatment to day 28Population: It was decided to not move forward with Arm2 of the study and no participants were enrolled in Arm 2.
Percentage of participants in Arm 2 who completed study drug treatment (DTG+1HP).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Measured at Days 28 and 42Population: It was decided to not move forward with Arm2 of the study and no participants were enrolled in Arm 2.
This evaluates the short-term impact on virologic suppression of DTG based ART when coadministered with 1HP by measuring the percentage of participants with plasma HIV-1 RNA levels \>50 copies/mL at study day 28 (after 4 weeks of DTG+1HP) and study day 42 (14 days after completing study treatment).
Outcome measures
Outcome data not reported
Adverse Events
Arm 1: DTG + INH + RPT
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm 1: DTG + INH + RPT
n=36 participants at risk
Participants received 50 mg of DTG orally twice daily (\~12 hours apart). Participants received 300 mg of INH and 600 mg of RPT orally each morning for 4 weeks.
Participants also received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH.
Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. Participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses.
Dolutegravir (DTG): Administered orally
Isoniazid (INH): Administered orally
Rifapentine (RPT): Administered orally
Antiretroviral Therapy (ART): Participants remained on DTG-based ARV treatment with 2 NRTIs (excluding TAF) during the study. NRTIs were not provided by the study. Arm 1 participants took non-study supply of DTG for morning doses, and study-supplied DTG for evening doses. For Arm 2 participants, DTG was to have come from non-study ARV supply.
Pyridoxine (Vitamin B6): Participants received 25 or 50 mg of pyridoxine (vitamin B6) with each dose of INH, based on the current local, national, or international dosing guidelines. Pyridoxine was not provided by the study.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.3%
3/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Eye disorders
Conjunctivitis allergic
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
General disorders
Pyrexia
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Infections and infestations
COVID-19
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Infections and infestations
Orchitis
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
Alanine aminotransferase increased
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
Aspartate aminotransferase increased
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
Blood bilirubin increased
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
Blood creatinine increased
|
8.3%
3/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
Glomerular filtration rate decreased
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
Weight decreased
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Investigations
White blood cell count decreased
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Nervous system disorders
Headache
|
8.3%
3/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
|
Vascular disorders
Hypertension
|
2.8%
1/36 • From start of study treatment to study completion at Day 49 or premature study discontinuation.
All participants who took at least one dose of RPT, at least one dose of INH, and at least 2 doses of DTG were included.
|
Additional Information
ACTG Clinicaltrials.gov Coordinator
ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company
Results disclosure agreements
- Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
- Publication restrictions are in place
Restriction type: OTHER