Trial Outcomes & Findings for Pharmacokinetics, Safety and Tolerability of Escalating Rifapentine Doses in Healthy Volunteers (NCT NCT01162486)
NCT ID: NCT01162486
Last Updated: 2019-05-07
Results Overview
Number of Participants with Grade 2 or higher adverse events over 26 days
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
37 participants
Primary outcome timeframe
26 days
Results posted on
2019-05-07
Participant Flow
Participant milestones
| Measure |
RPT 1
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 2
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 3
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Rifampin Control
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
7
|
6
|
8
|
|
Overall Study
Took at Least One Dose Study Drug
|
6
|
6
|
7
|
6
|
8
|
|
Overall Study
COMPLETED
|
6
|
5
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
0
|
2
|
Reasons for withdrawal
| Measure |
RPT 1
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 2
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 3
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Rifampin Control
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
|---|---|---|---|---|---|
|
Overall Study
low ANC
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
vomited Rifampin/ gagged with midazolam
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
elevated LFTs
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Pregnancy
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Pharmacokinetics, Safety and Tolerability of Escalating Rifapentine Doses in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Rifampin Control
n=8 Participants
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 1
n=7 Participants
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 2
n=7 Participants
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 3
n=7 Participants
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
n=8 Participants
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
37 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
39 years
n=5 Participants
|
50 years
n=7 Participants
|
44 years
n=5 Participants
|
41 years
n=4 Participants
|
47 years
n=21 Participants
|
44 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
31 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
7 participants
n=4 Participants
|
8 participants
n=21 Participants
|
37 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 26 daysPopulation: Four withdrew prior to receiving study rifamycin so were not included in the safety population
Number of Participants with Grade 2 or higher adverse events over 26 days
Outcome measures
| Measure |
RPT 3
n=7 Participants
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
n=6 Participants
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Rifampin Control
n=8 Participants
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 1
n=6 Participants
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 2
n=6 Participants
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
|---|---|---|---|---|---|
|
Number of Participants With Grade 2 or Higher Adverse Events Over the Course of the 26 Day Trial
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: days: 2, 15Population: These patients completed PK visits on Day 2 and 15 (Three participants in this non-control group - subdivided into 4- did not complete the study). Reasons provided in the participant flow session
To determine and compare the steady-state pharmacokinetics and dose linearity of escalating daily doses of rifapentine in dose cohorts of 5 mg/kg, 10 mg/kg, 15 mg/kg and 20 mg/kg in healthy volunteers after a single dose (Day 2) or multiple doses (Day 15)
Outcome measures
| Measure |
RPT 3
n=6 Participants
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Rifampin Control
n=5 Participants
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 1
n=5 Participants
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 2
n=6 Participants
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
|---|---|---|---|---|---|
|
Pharmacokinetics (AUC of RPT Over 24 Hours Post-dose)
RPT AUC, Day 2 single dose
|
403 (mcg*h/ml)
Interval 357.0 to 452.0
|
—
|
128 (mcg*h/ml)
Interval 101.0 to 157.0
|
242 (mcg*h/ml)
Interval 231.0 to 260.0
|
363 (mcg*h/ml)
Interval 310.0 to 430.0
|
|
Pharmacokinetics (AUC of RPT Over 24 Hours Post-dose)
RPT AUC, Day 15 multiple dose
|
483 (mcg*h/ml)
Interval 414.0 to 546.0
|
—
|
218 (mcg*h/ml)
Interval 142.0 to 251.0
|
330 (mcg*h/ml)
Interval 284.0 to 340.0
|
560 (mcg*h/ml)
Interval 401.0 to 735.0
|
SECONDARY outcome
Timeframe: days: 1, 15Population: 29 participants completed both midazolam PK visits; one person in RPT1 visit was not analyzed because his samples were zero and was found to have been non-compliant with regimen
To compare and describe, the pharmacokinetics of single-dose midazolam alone (Day 1) versus midazolam co-administered with either steady-state rifapentine at multiple daily doses (5, 10, 15, and 20 mg/kg) or rifampin at 10 mg/kg daily (Day 15)
Outcome measures
| Measure |
RPT 3
n=6 Participants
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
n=6 Participants
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Rifampin Control
n=6 Participants
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 1
n=5 Participants
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 2
n=5 Participants
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
|---|---|---|---|---|---|
|
Midazolam, AUC Over 12 Hours Post-dose
AUC 0-12 Midazolam alone (Day 1)
|
204 ng*h/ml
Interval 158.0 to 255.0
|
173 ng*h/ml
Interval 118.0 to 270.0
|
151 ng*h/ml
Interval 116.0 to 197.0
|
150 ng*h/ml
Interval 108.0 to 238.0
|
114 ng*h/ml
Interval 111.0 to 128.0
|
|
Midazolam, AUC Over 12 Hours Post-dose
AUC 0-12 Midazolam with RIF (Day 15)
|
14.0 ng*h/ml
Interval 12.6 to 15.2
|
11.7 ng*h/ml
Interval 8.8 to 14.6
|
26.9 ng*h/ml
Interval 10.0 to 55.8
|
14.2 ng*h/ml
Interval 7.34 to 20.1
|
10.2 ng*h/ml
Interval 10.0 to 10.4
|
SECONDARY outcome
Timeframe: day 3Population: This outcome was not assessed because data was not collected
To determine the effects of polymorphisms of transporter genes on rifampin and rifapentine PK parameters
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: days 2, 3, 7, 10, 15, 16, 17, 18Population: This outcome was not assessed because data was not collected
To develop methods for determination of rifapentine concentrations from dried blood spots on sampling paper
Outcome measures
Outcome data not reported
Adverse Events
RPT 2
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
RPT 3
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
RPT 4
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Rifampin Control
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
RPT 1
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
RPT 2
n=6 participants at risk
RPT Cohort 2 - 10 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 3
n=7 participants at risk
RPT Cohort 3 - 15 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 15 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 4
n=6 participants at risk
RPT Cohort 4 - 20 mg/kg
rifapentine and midazolam: rifapentine - tablet, 20 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
Rifampin Control
n=8 participants at risk
Rifampin + midazolam
Rifampin \& midazolam: rifampin - tablet, 10 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
RPT 1
n=6 participants at risk
RPT Cohort 1 - 5 mg/kg
rifapentine \& midazolam: rifapentine - tablet, 5 mg/kg, daily 15 days midazolam - liquid syrup, 15 mg, days 1 and 15
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gas
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6 • Number of events 1
|
28.6%
2/7 • Number of events 2
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomitting
|
0.00%
0/6
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
General disorders
fever
|
0.00%
0/6
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
|
General disorders
Dizziness
|
0.00%
0/6
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
0.00%
0/8
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Neutropenia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/7
|
0.00%
0/6
|
25.0%
2/8 • Number of events 2
|
0.00%
0/6
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
0.00%
0/6
|
14.3%
1/7 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/6
|
|
General disorders
Lymphopenia
|
0.00%
0/6
|
28.6%
2/7 • Number of events 2
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
|
Endocrine disorders
Hyperglycemia
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Hypertransaminasemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/8
|
0.00%
0/6
|
|
General disorders
Leukopenia
|
0.00%
0/6
|
0.00%
0/7
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/6
|
Additional Information
Dr. Kelly E. Dooley
Johns Hopkins University School of Medicine
Phone: 410-955-3100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place