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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01399788
First received: July 13, 2011
Last updated: May 9, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Healthy Volunteers
Drug: Myrin P Forte
Drug: Single drug references
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open Label, Single Dose, 2-Way Cross-Over Randomized Bioequivalence Study Comparing a Fixed Dose Combination Formulation, Myrin®-p Forte, (Contains 150 Mg Rifampicin, 75 Mg Isoniazid, 275 Mg Ethambutol and 400 Mg Pyrazinamide Per Tablet) to an Equivalent Dose of Single Drug Reference Preparations of Rifampicin, Isoniazid, Ethambutol and Pyrazinamide Following Oral Administration in Healthy Adults Under Fasting Conditions

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose ] [ Designated as safety issue: No ]
  • Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞]) [ Time Frame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose ] [ Designated as safety issue: No ]
    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-∞).

  • Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Plasma Decay Half-life (t1/2) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: July 2011
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1.0
Test Myrin P Forte Contains 150mg Rifampicin, 75mg Isoniazid, 275mg Ethambutol, 400mg Pyrazinamide
Drug: Myrin P Forte
Tablet containing Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, given once daily, single dose
Active Comparator: 2.0
Reference Single drug reference preparations contain Rifampicin, Isoniazid, Ethambutol, Pyrazinamide
Drug: Single drug references
containing Rifampicin, Isoniazid, Ethambutol and Pyrazinamide as single agents

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399788

Locations
Singapore
Pfizer Investigational Site
Singapore, Singapore, 188770
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01399788     History of Changes
Other Study ID Numbers: B3801002
Study First Received: July 13, 2011
Results First Received: February 22, 2012
Last Updated: May 9, 2012
Health Authority: Singapore: Institutional Ethics Committee

Keywords provided by Pfizer:
Bioequivalence
Healthy Volunteers

Additional relevant MeSH terms:
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Antibiotics, Antitubercular
Enzyme Inhibitors
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014