Trial Outcomes & Findings for Bioequivalence Study Comparing Rifampicin In A Fixed-Dose Combination (Rifampicin+Isoniazid, Myrin© 2) And The Reference Drug (Rifampicin, Rimactane®) (NCT NCT01311505)
NCT ID: NCT01311505
Last Updated: 2012-07-30
Results Overview
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
COMPLETED
PHASE1
21 participants
0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hours (hrs) post-dose
2012-07-30
Participant Flow
Out of 22 participants enrolled, only 21 participants were randomized since 1 participant withdrew from the study.
Participant milestones
| Measure |
Myrin 2 First, Then Rimactane
Single oral dose of 2 fixed dose combination (FDC) tablets of Myrin 2 (each tablet contains 150 milligram (mg) rifampicin and 75 mg isoniazid) in first intervention period, and single oral dose of Rimactane capsule (300 mg rifampicin) in second intervention period. A washout period of at least 7 days was maintained between each period.
|
Rimactane First, Then Myrin 2
Single oral dose of Rimactane capsule (300 mg rifampicin) in first intervention period; and single oral dose of 2 FDC tablets of Myrin 2 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) in second intervention period. A washout period of at least 7 days was maintained between each period.
|
|---|---|---|
|
First Intervention Period
STARTED
|
10
|
11
|
|
First Intervention Period
COMPLETED
|
10
|
10
|
|
First Intervention Period
NOT COMPLETED
|
0
|
1
|
|
Washout Period (at Least 7 Days)
STARTED
|
10
|
10
|
|
Washout Period (at Least 7 Days)
COMPLETED
|
10
|
10
|
|
Washout Period (at Least 7 Days)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention Period
STARTED
|
10
|
10
|
|
Second Intervention Period
COMPLETED
|
10
|
10
|
|
Second Intervention Period
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Myrin 2 First, Then Rimactane
Single oral dose of 2 fixed dose combination (FDC) tablets of Myrin 2 (each tablet contains 150 milligram (mg) rifampicin and 75 mg isoniazid) in first intervention period, and single oral dose of Rimactane capsule (300 mg rifampicin) in second intervention period. A washout period of at least 7 days was maintained between each period.
|
Rimactane First, Then Myrin 2
Single oral dose of Rimactane capsule (300 mg rifampicin) in first intervention period; and single oral dose of 2 FDC tablets of Myrin 2 (each tablet contains 150 mg rifampicin and 75 mg isoniazid) in second intervention period. A washout period of at least 7 days was maintained between each period.
|
|---|---|---|
|
First Intervention Period
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Bioequivalence Study Comparing Rifampicin In A Fixed-Dose Combination (Rifampicin+Isoniazid, Myrin© 2) And The Reference Drug (Rifampicin, Rimactane®)
Baseline characteristics by cohort
| Measure |
Participants Eligible for Analysis
n=20 Participants
Includes participants randomized to receive Myrin 2 first and Rimactane first and who had completed the study. It excludes 1 participant who did not meet the weight requirement for the study (protocol violator).
|
|---|---|
|
Age, Customized
18 to 22 years
|
12 participants
n=5 Participants
|
|
Age, Customized
23 to 27 years
|
4 participants
n=5 Participants
|
|
Age, Customized
28 to 32 years
|
2 participants
n=5 Participants
|
|
Age, Customized
33 to 37 years
|
2 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hours (hrs) post-dosePopulation: Pharmacokinetic (PK) parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=20 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC [0-t])
|
38.59 microgram*hour/milliliter (mcg*h/mL)
Geometric Coefficient of Variation 24.99
|
38.81 microgram*hour/milliliter (mcg*h/mL)
Geometric Coefficient of Variation 21.95
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dosePopulation: PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=20 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
7.89 mcg/mL
Geometric Coefficient of Variation 24.89
|
8.02 mcg/mL
Geometric Coefficient of Variation 22.35
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dosePopulation: PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=20 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax)
|
2.0 hrs
Interval 1.0 to 3.0
|
1.0 hrs
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dosePopulation: PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
AUC (0-∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=20 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞])
|
47.72 mcg*hr/mL
Geometric Coefficient of Variation 30.54
|
47.15 mcg*hr/mL
Geometric Coefficient of Variation 25.32
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dosePopulation: PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=20 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Plasma Decay Half-life (t1/2)
|
4.0750 hrs
Standard Deviation 1.0777
|
3.8635 hrs
Standard Deviation 0.8347
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dosePopulation: PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
AUC%extrapolated is the extrapolated area under the plasma concentration time profile following the last measured concentration. It is calculated as (AUC \[0-∞\] minus AUC\[0-10\])\*100/ AUC (0-∞), where AUC (0-∞) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-∞) and AUC(0-10) = area under the plasma concentration time-curve from zero (pre-dose) to the last quantifiable concentration.
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=20 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated)
|
18.84 Percent AUC
Geometric Coefficient of Variation 38.47
|
17.53 Percent AUC
Geometric Coefficient of Variation 30.23
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening and Follow-up (1 week post-baseline)Population: Safety population included participants who received at least 1 dose of study medication.
Participants were evaluated for following safety laboratory tests: Hematology, chemistry, urinalysis.
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=21 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Number of Participants With Abnormal Safety Laboratory Test Values
Screening
|
0 participants
|
0 participants
|
|
Number of Participants With Abnormal Safety Laboratory Test Values
Follow-up
|
0 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)Population: Data was not summarized since supine systolic and diastolic BP remained within normal limits throughout the study and there were no significant deviations from baseline.
Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)Population: Data was not summarized since pulse rate remained within normal limits throughout the study and there were no significant deviations from baseline.
Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)Population: Data was not summarized since oral temperature remained within normal limits throughout the study and there were no significant deviations from baseline.
Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)Population: Data was not summarized since respiratory rate remained within normal limits throughout the study and there were no significant deviations from baseline.
Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline (Day 0), Day 1 and Follow-up (1 week post-baseline)Population: Safety population included participants who received at least 1 dose of study medication.
Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship.
Outcome measures
| Measure |
Myrin 2
n=20 Participants
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin and 75 mg isoniazid.
|
Rimactane
n=21 Participants
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Day 0
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Day 1
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Follow-up
|
0 participants
|
0 participants
|
Adverse Events
Myrin 2
Rimactane
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place