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

NCT01399788 | Completed Phase 1 Results

• 1 other identifier: B3801002
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

Bioequivalence; Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

  Area under the plasma concentration-time curve from time zero (pre-dose) to the time of last measured 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

• 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 Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide

  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.

  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

• Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide

  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.

  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

Secondary Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (2)

1.0

ACTIVE COMPARATOR

Test Myrin P Forte Contains 150mg Rifampicin, 75mg Isoniazid, 275mg Ethambutol, 400mg Pyrazinamide

Drug: Myrin P Forte

2.0

ACTIVE COMPARATOR

Reference Single drug reference preparations contain Rifampicin, Isoniazid, Ethambutol, Pyrazinamide

Drug: Single drug references

Interventions

Myrin P Forte DRUG

Tablet containing Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, given once daily, single dose

1.0

Single drug references DRUG

containing Rifampicin, Isoniazid, Ethambutol and Pyrazinamide as single agents

2.0

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Investigational Site

Singapore, 188770, Singapore

Location

Related Publications (1)

• Wang HF, Wang R, O'Gorman M, Crownover P, Naqvi A, Jafri I. Bioequivalence of fixed-dose combination Myrin(R)-P Forte and reference drugs in loose combination. Int J Tuberc Lung Dis. 2013 Dec;17(12):1596-601. doi: 10.5588/ijtld.13.0190.

  PMID: 24200275 DERIVED

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2011
• First Posted: July 22, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: April 5, 2017
• Results First Posted: March 16, 2012

Record last verified: 2017-03

Locations

SG (1)