Bioequivalence Study Comparing Rifampicin In A Fixed-Dose... | NCT01311505

Status Module

Label	Type	Description	Intervention Names
A	Active Comparator	Test	Drug: Myrin© 2 (Rifampicin + Isoniazid)
B	Active Comparator	Reference	Drug: Rimactane® (Rifampicin)

Name	Type	Description	Arm Group Labels	Other Names
Myrin© 2 (Rifampicin + Isoniazid)	Drug	Two (2) fixed-dose combination tablets each containing Rifampicin 150 mg and Isoniazid 75 mg	A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC [0-t])	AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)	0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hours (hrs) post-dose
Maximum Observed Plasma Concentration (Cmax)		0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose

Secondary Outcomes

Measure	Description	Time Frame
Time to Reach Maximum Observed Plasma Concentration (Tmax)		0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞])	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-∞).

Other Outcomes

Measure	Description	Time Frame
Number of Participants With Abnormal Safety Laboratory Test Values	Participants were evaluated for following safety laboratory tests: Hematology, chemistry, urinalysis.	Screening and Follow-up (1 week post-baseline)
Clinically Significant Change From Baseline Supine Blood Pressure (BP)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Healthy male subjects between the ages of 18 and 55 years, inclusive.
Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
An informed consent document signed and dated by the subject.
Subjects willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
Any condition possibly affecting drug absorption (e.g., gastrectomy).
A positive urine drug screen.
History of regular alcohol consumption exceeding 21 drinks/week (1 drink = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of hard liquor) within 6 months of screening.
Treatment with an investigational drug within 3 months (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
12-lead ECG demonstrating QTc >450 msec at screening. If QTc exceeds 450 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the subject's eligibility.
History of previous treatment for TB or is suspected of suffering from TB.
Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal medication, herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen / paracetamol may be used at doses of less than 1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.
Blood donation of approximately 1 pint (500 ml) within 56 days prior to dosing.
A history of hypersensitivity to any of the study medications or related substances, or to any of the ingredients used in the study drug formulations.
Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
Recent history of diarrhea (2 weeks).
Recent use of oral (2 weeks) or IV (2-3 months) antibiotics to assure normal bowel flora at study start.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Dasmariñas		4114	Philippines

Label	URL
To obtain contact information for a study center near you, click here.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Participants Eligible for Analysis	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).

Units	Counts
Participants	BG00020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC [0-t])

AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

microgram*hour/milliliter (mcg*h/mL)

0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hours (hrs) post-dose

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.

Units	Counts
Participants	OG00020 OG00120

Title

Denominators

Categories

Title	Measurements
	OG00038.59± 24.99 OG00138.81± 21.95

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.					Ratio of adjusted geometric means	98.90			2-Sided	90	92.98	105.20				No	Superiority or Other

Primary

Maximum Observed Plasma Concentration (Cmax)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane capsule (300 mg capsule) in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax)

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.

Posted

Median

Full Range

hrs

0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Secondary

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞])

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-∞).

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg*hr/mL

0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.

Units	Counts
Participants

Secondary

Plasma Decay Half-life (t1/2)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

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.

Posted

Mean

Standard Deviation

hrs

0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Secondary

Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated)

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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Percent AUC

0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane capsule (300 mg rifampicin) in either first intervention period or second intervention period.

Units

Other Pre-specified

Number of Participants With Abnormal Safety Laboratory Test Values

Participants were evaluated for following safety laboratory tests: Hematology, chemistry, urinalysis.

Safety population included participants who received at least 1 dose of study medication.

Posted

Number

participants

Screening and Follow-up (1 week post-baseline)

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Other Pre-specified

Clinically Significant Change From Baseline Supine Blood Pressure (BP)

Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.

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.

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Other Pre-specified

Clinically Significant Change From Baseline Pulse Rate

Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.

Data was not summarized since pulse rate remained within normal limits throughout the study and there were no significant deviations from baseline.

Posted

Mean

Standard Deviation

beats per minute

Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Other Pre-specified

Clinically Significant Change From Baseline Oral Temperature

Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.

Data was not summarized since oral temperature remained within normal limits throughout the study and there were no significant deviations from baseline.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Other Pre-specified

Clinically Significant Change From Baseline Respiratory Rate

Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.

Data was not summarized since respiratory rate remained within normal limits throughout the study and there were no significant deviations from baseline.

Posted

Mean

Standard Deviation

respirations/minute

Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline)

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Participants With Adverse Events (AEs)

Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship.

Safety population included participants who received at least 1 dose of study medication.

Posted

Number

participants

Baseline (Day 0), Day 1 and Follow-up (1 week post-baseline)

ID	Title	Description
OG000	Myrin 2	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.
OG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

ID	Term
D009164	Mycobacterium Infections
D000193	Actinomycetales Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
D012293	Rifampin
D007538	Isoniazid

ID	Term
D012294	Rifamycins
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D006834	Hydrazines
D009930	Organic Chemicals
D007539	Isonicotinic Acids
D000147	Acids, Heterocyclic
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Myrin 2	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.			0	20	0	20
EG001	Rimactane	Single oral dose of reference drug Rimactane 300 mg capsule in either first intervention period or second intervention period.			0	21	0	21