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Bioequivalence Study Comparing Rifampicin In A Fixed-Dose Combination (Rifampicin+Isoniazid, Myrin© 2) And The Reference Drug (Rifampicin, Rimactane®)

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ClinicalTrials.gov Identifier: NCT01311505
Recruitment Status : Completed
First Posted : March 9, 2011
Results First Posted : July 30, 2012
Last Update Posted : July 30, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Tuberculosis
Interventions Drug: Myrin© 2 (Rifampicin + Isoniazid)
Drug: Rimactane® (Rifampicin)
Enrollment 21
Recruitment Details  
Pre-assignment Details Out of 22 participants enrolled, only 21 participants were randomized since 1 participant withdrew from the study.
Arm/Group Title Myrin 2 First, Then Rimactane Rimactane First, Then Myrin 2
Hide Arm/Group Description 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. 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.
Period Title: First Intervention Period
Started 10 11
Completed 10 10
Not Completed 0 1
Reason Not Completed
Protocol Violation             0             1
Period Title: Washout Period (at Least 7 Days)
Started 10 10
Completed 10 10
Not Completed 0 0
Period Title: Second Intervention Period
Started 10 10
Completed 10 10
Not Completed 0 0
Arm/Group Title Participants Eligible for Analysis
Hide Arm/Group Description 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).
Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants
18 to 22 years 12
23 to 27 years 4
28 to 32 years 2
33 to 37 years 2
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
0
   0.0%
Male
20
 100.0%
1.Primary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC [0-t])
Hide Description AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Time Frame 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hours (hrs) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
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.
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram*hour/milliliter (mcg*h/mL)
38.59
(24.99%)
38.81
(21.95%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myrin 2, Rimactane
Comments 20 participants (10 per sequence) provided at least 98% power that 90% confidence interval (CI) for ratio of test to reference for AUC(0-t) of rifampicin lie within acceptance region of 80%-125%. Intra-participant coefficient of variation (CV) estimate of approximately 13.48% for AUC(0-t) was used for this power calculation. Natural log transformed AUC(0-t) was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 98.90
Confidence Interval (2-Sided) 90%
92.98 to 105.20
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
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.
Single oral dose of reference drug Rimactane capsule (300 mg capsule) in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg/mL
7.89
(24.89%)
8.02
(22.35%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myrin 2, Rimactane
Comments 20 participants (10 per sequence) provided at least 94% power that 90% CI for ratio of test to reference for Cmax of rifampicin lie within acceptance region of 80%-125%. Intra-participant CV estimate of approximately 16.43% for Cmax was used for this power calculation. Natural log transformed Cmax was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 98.24
Confidence Interval (2-Sided) 90%
87.77 to 109.97
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax)
Hide Description [Not Specified]
Time Frame 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
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.
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 20
Median (Full Range)
Unit of Measure: hrs
2.0
(1.0 to 3.0)
1.0
(1.0 to 3.0)
4.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞])
Hide Description 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-∞).
Time Frame 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
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.
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mcg*hr/mL
47.72
(30.54%)
47.15
(25.32%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Myrin 2, Rimactane
Comments Natural log transformed AUC(0-∞) of rifampicin was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of adjusted geometric means
Estimated Value 100.25
Confidence Interval (2-Sided) 90%
94.44 to 106.41
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Plasma Decay Half-life (t1/2)
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
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.
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: hrs
4.0750  (1.0777) 3.8635  (0.8347)
6.Secondary Outcome
Title Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated)
Hide Description 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.
Time Frame 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
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.
Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 20
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percent AUC
18.84
(38.47%)
17.53
(30.23%)
7.Other Pre-specified Outcome
Title Number of Participants With Abnormal Safety Laboratory Test Values
Hide Description Participants were evaluated for following safety laboratory tests: Hematology, chemistry, urinalysis.
Time Frame Screening and Follow-up (1 week post-baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least 1 dose of study medication.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid.
Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 21
Measure Type: Number
Unit of Measure: participants
Screening 0 0
Follow-up 0 0
8.Other Pre-specified Outcome
Title Clinically Significant Change From Baseline Supine Blood Pressure (BP)
Hide Description Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Time Frame Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid.
Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Other Pre-specified Outcome
Title Clinically Significant Change From Baseline Pulse Rate
Hide Description Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Time Frame Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not summarized since pulse rate remained within normal limits throughout the study and there were no significant deviations from baseline.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid.
Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Other Pre-specified Outcome
Title Clinically Significant Change From Baseline Oral Temperature
Hide Description Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Time Frame Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not summarized since oral temperature remained within normal limits throughout the study and there were no significant deviations from baseline.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid.
Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Other Pre-specified Outcome
Title Clinically Significant Change From Baseline Respiratory Rate
Hide Description Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
Time Frame Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not summarized since respiratory rate remained within normal limits throughout the study and there were no significant deviations from baseline.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid.
Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Other Pre-specified Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship.
Time Frame Baseline (Day 0), Day 1 and Follow-up (1 week post-baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included participants who received at least 1 dose of study medication.
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description:
Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid.
Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
Overall Number of Participants Analyzed 20 21
Measure Type: Number
Unit of Measure: participants
Day 0 0 0
Day 1 0 0
Follow-up 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Myrin 2 Rimactane
Hide Arm/Group Description Single oral dose of 2 FDC tablets of Myrin 2 (Test) in either first intervention period or second intervention period. Each tablet contains 150 rifampicin and 75 mg isoniazid. Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.
All-Cause Mortality
Myrin 2 Rimactane
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Myrin 2 Rimactane
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/21 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Myrin 2 Rimactane
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   0/21 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01311505     History of Changes
Other Study ID Numbers: B3801001
First Submitted: February 15, 2011
First Posted: March 9, 2011
Results First Submitted: March 23, 2012
Results First Posted: July 30, 2012
Last Update Posted: July 30, 2012