Clinical trial NCT01399788: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Bioequivalence
Healthy Volunteers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-07-22
Enrollment: 36
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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


Eligibility 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.

Primary outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose
measure: Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide
timeFrame: 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
measure: Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide
timeFrame: 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:
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞])
timeFrame: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose
measure: Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide
timeFrame: 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
measure: Plasma Decay Half-life (t1/2)
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 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
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.