A Bioequivalence Study Comparing A Fixed Dose Combination Formulation Of Myrin P Forte That Contains Rifampicin, Isoniazid, Ethambutol And Pyrazinamide Per Tablet To An Equivalent Dose Of Single Drug Reference Preparations Of Similar Combination Following Oral Administration In Healthy Adults

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Myrin P Forte; Drug: Single drug references

• Registration Number: NCT01399788
• Lead Sponsor: Pfizer

Brief Summary

This is a bioequivalence trial to evaluate the bioequivalence of Myrin P Forte against reference drug in healthy volunteers.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07
• Study First Submitted: 2011-07-13
• Study First Submitted QC: 2011-07-20
• Study First Posted: 2011-07-22
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Results First Submitted: 2012-02-22
• Results First Submitted QC: 2012-02-22
• Results First Posted: 2012-03-16
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-07
• Last Update Posted: 2017-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Healthy, male or female, 21 to 55 years of age, body weight no less than 55 kg, Body mass index (BMI) of 17.5 to 30.5 kg/m2. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead electrocardiogram (ECG) or clinical laboratory tests.
• An informed consent document signed and dated by the subject.
• Subjects who are willing and able to comply with all 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, allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing), positive Hepatitis B surface antigen or Human Immunodeficiency Virus (HIV) serology results.
• pregnant or nursing female,
• alcohol, drug, smoke user,
• sensitive to any study medication or related component,
• History or active gout,
• History or active tuberculosis,
• Known optic neuritis or other ophthalmological conditions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1.0	Myrin P Forte	Test Myrin P Forte Contains 150mg Rifampicin, 75mg Isoniazid, 275mg Ethambutol, 400mg Pyrazinamide
2.0	Single drug references	Reference Single drug reference preparations contain Rifampicin, Isoniazid, Ethambutol, Pyrazinamide

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hours (hrs) post-dose	Area under the plasma concentration-time curve from time zero (pre-dose) to the time of last measured concentration (AUClast).
Maximum Observed Plasma Concentration (Cmax)	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose
Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post-dose	It is obtained from Cmax divided by dose and then multiplied by 1500. The test and reference for pyrazinamide were given at different doses, so dose-normalized parameters were used for analysis for adjusting the dose effect on bioequivalence conclusion.
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post-dose	AUClast\[dn\] = Dose normalized area under the plasma concentration-time curve (AUC\[dn\]) from time zero (pre-dose) to the time of last measured concentration. It is obtained from AUClast divided by dose and then multiplied by 1500. The test and reference for pyrazinamide were given at different doses, so dose-normalized parameters were used for analysis for adjusting the dose effect on bioequivalence conclusion.

Secondary Outcome Measures

Name	Time	Method
Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hrs post-dose	AUC \[0-∞\]\[dn\] = Dose normalized area under the plasma concentration versus time curve (AUC\[dn\]) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-∞) divided by dose and then multiplied by 1500. The test and reference for pyrazinamide were given at different doses, so dose-normalized parameters were used for analysis for adjusting the dose effect on bioequivalence conclusion.
Time to Reach Maximum Observed Plasma Concentration (Tmax)	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose for rifampicin, isoniazid and ethambutol and additional 36 and 48 hrs post-dose for pyrazinamide
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞])	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose	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-∞).
Plasma Decay Half-life (t1/2)	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose for rifampicin, isoniazid and ethambutol and additional 36 and 48 hrs post-dose for pyrazinamide	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇸🇬 Singapore, Singapore