Trial Outcomes & Findings for Doravirine, Rifapentine and Isoniazid Interaction (NCT NCT03886701)
NCT ID: NCT03886701
Last Updated: 2020-03-27
Results Overview
Doravirine maximum observed concentration during the dosing interval
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
11 participants
Primary outcome timeframe
Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Results posted on
2020-03-27
Participant Flow
Participant milestones
| Measure |
Study Particpants
Eleven healthy volunteers enrolled into the study. For period 1 (study days 1-4), participants will be given doravirine 100mg oral tablets dosed twice-daily on study days 1-4. For period 2 (study days 7-21), oral 100mg doravirine will be dosed twice-daily. Weight-based rifapentine and isoniazid (as recommended by the CDC) will be given orally once-weekly on study days 7, 14, and 21.
|
|---|---|
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Period 1: Study Days 1-4
STARTED
|
11
|
|
Period 1: Study Days 1-4
COMPLETED
|
11
|
|
Period 1: Study Days 1-4
NOT COMPLETED
|
0
|
|
Period 2: Study Days 7-21
STARTED
|
11
|
|
Period 2: Study Days 7-21
COMPLETED
|
11
|
|
Period 2: Study Days 7-21
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Doravirine, Rifapentine and Isoniazid Interaction
Baseline characteristics by cohort
| Measure |
Study Particpants
n=11 Participants
Eleven healthy volunteers enrolled into the study.
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|---|---|
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Age, Continuous
|
50 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
8 Participants
n=5 Participants
|
|
Weight
|
92.9 Kilogram
STANDARD_DEVIATION 11.3 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-doseDoravirine maximum observed concentration during the dosing interval
Outcome measures
| Measure |
Period 1
n=11 Participants
DOR twice-daily alone (Study days 1-4)
Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
|
Period 2
n=11 Participants
DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
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|---|---|---|
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Doravirine Maximum Concentration (Cmax)
|
1.7 ug/mL
Interval 1.5 to 2.0
|
1.3 ug/mL
Interval 1.1 to 1.5
|
PRIMARY outcome
Timeframe: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-doseDoravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
Outcome measures
| Measure |
Period 1
n=11 Participants
DOR twice-daily alone (Study days 1-4)
Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
|
Period 2
n=11 Participants
DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
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|---|---|---|
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Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)
|
17.3 hr x ug/mL
Interval 14.9 to 20.0
|
12.3 hr x ug/mL
Interval 10.4 to 14.3
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PRIMARY outcome
Timeframe: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-doseDoravirine apparent oral clearance derived from plasma sampling
Outcome measures
| Measure |
Period 1
n=11 Participants
DOR twice-daily alone (Study days 1-4)
Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
|
Period 2
n=11 Participants
DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
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|---|---|---|
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Doravirine Oral Clearance (CL/F)
|
5.9 L/hr
Geometric Coefficient of Variation 24
|
8.4 L/hr
Geometric Coefficient of Variation 26.1
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SECONDARY outcome
Timeframe: Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study)Safety and tolerability
Outcome measures
| Measure |
Period 1
n=11 Participants
DOR twice-daily alone (Study days 1-4)
Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
|
Period 2
n=11 Participants
DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
|
|---|---|---|
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Adverse Event
Nausea/vomiting
|
1 participants
|
0 participants
|
|
Adverse Event
Dysuria
|
0 participants
|
1 participants
|
|
Adverse Event
Fever
|
0 participants
|
1 participants
|
|
Adverse Event
Headache
|
0 participants
|
1 participants
|
|
Adverse Event
Chills
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0 participants
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1 participants
|
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Adverse Event
Catheter site pain and redness
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3 participants
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2 participants
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Adverse Events
Period 1
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Period 2
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Period 1
n=11 participants at risk
DOR twice-daily alone (Study days 1-4)
Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
|
Period 2
n=11 participants at risk
DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
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|---|---|---|
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Gastrointestinal disorders
Nausea/vomiting
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9.1%
1/11 • Daily for the duration of the study and 7-10 days post-study.
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0.00%
0/11 • Daily for the duration of the study and 7-10 days post-study.
|
|
Renal and urinary disorders
Dysuria
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0.00%
0/11 • Daily for the duration of the study and 7-10 days post-study.
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9.1%
1/11 • Daily for the duration of the study and 7-10 days post-study.
|
|
General disorders
Fever
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0.00%
0/11 • Daily for the duration of the study and 7-10 days post-study.
|
9.1%
1/11 • Daily for the duration of the study and 7-10 days post-study.
|
|
Nervous system disorders
Headache
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0.00%
0/11 • Daily for the duration of the study and 7-10 days post-study.
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9.1%
1/11 • Daily for the duration of the study and 7-10 days post-study.
|
|
General disorders
Chills
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0.00%
0/11 • Daily for the duration of the study and 7-10 days post-study.
|
9.1%
1/11 • Daily for the duration of the study and 7-10 days post-study.
|
|
General disorders
Catheter site pain and redness
|
27.3%
3/11 • Daily for the duration of the study and 7-10 days post-study.
|
18.2%
2/11 • Daily for the duration of the study and 7-10 days post-study.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place