Bioequivalence Study Comparing Rifampicin In A Fixed-Dose Combination (Rifampicin+Isoniazid, Myrin© 2) And The Reference Drug (Rifampicin, Rimactane®)

• ClinicalTrials.gov Identifier: NCT01311505
• Recruitment Status: Completed
• First Posted: March 9, 2011
• Results First Posted: July 30, 2012
• Last Update Posted: July 30, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This study is done to demonstrate bioequivalence of rifampicin component in Myrin© 2 Fixed-Dose Combination Tablet (each contains 75 mg isoniazid and 150 mg rifampicin, Pfizer Inc) with equivalent dose of the reference Rimactane® capsule (each contains 300 mg rifampicin, Novartis Sandoz) in healthy Filipino male subjects. This study also aims to determine the safety and tolerability of Myrin© 2 tablets and Rimactane® capsules in these subjects.

Condition or disease	Intervention/treatment	Phase
Tuberculosis	Drug: Myrin© 2 (Rifampicin + Isoniazid); Drug: Rimactane® (Rifampicin)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Single Dose, Randomized, Two-Way Cross-Over Bioequivalence Study Comparing Rifampicin In A Fixed-Dose Combination Rifampicin + Isoniazid (Myrin© 2, Pfizer Inc) Tablet With The Reference Drug (Rimactane®, Novartis Sandoz) Capsule In Healthy Filipino Male Subjects
• Study Start Date: April 2011
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: May 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A; Test	Drug: Myrin© 2 (Rifampicin + Isoniazid); Two (2) fixed-dose combination tablets each containing Rifampicin 150 mg and Isoniazid 75 mg; Other Name: Myrin© 2 (Pfizer Inc.)
Active Comparator: B; Reference	Drug: Rimactane® (Rifampicin); One (1) capsule of Rifampicin 300 mg; Other Name: Rimactane® (Novartis Sandoz)

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose ]
2. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞]) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 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-∞).
3. Plasma Decay Half-life (t1/2) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose ]
   Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
4. Extrapolated Area Under the Curve (AUC Percent [%] Extrapolated) [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 6, 8 and 10 hrs post-dose ]
   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.

Other Outcome Measures:

1. Number of Participants With Abnormal Safety Laboratory Test Values [ Time Frame: Screening and Follow-up (1 week post-baseline) ]
   Participants were evaluated for following safety laboratory tests: Hematology, chemistry, urinalysis.
2. Clinically Significant Change From Baseline Supine Blood Pressure (BP) [ Time Frame: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline) ]
   Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
3. Clinically Significant Change From Baseline Pulse Rate [ Time Frame: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline) ]
   Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
4. Clinically Significant Change From Baseline Oral Temperature [ Time Frame: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline) ]
   Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
5. Clinically Significant Change From Baseline Respiratory Rate [ Time Frame: Baseline (Day 0), Day 1 (Hour 10), and follow-up (1 week post-baseline) ]
   Mean change: vital sign value at observation (Day 1 and follow-up) minus vital sign value at baseline.
6. Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline (Day 0), Day 1 and Follow-up (1 week post-baseline) ]
   Any untoward medical occurrence in a participant who received study treatment was considered an AE without regard to possibility of causal relationship.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Philippines

Pfizer Investigational Site

Dasmariñas City, Philippines, 4114

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01311505
• Other Study ID Numbers: B3801001
• First Posted: March 9, 2011
• Results First Posted: July 30, 2012
• Last Update Posted: July 30, 2012
• Last Verified: June 2012

Keywords provided by Pfizer:

bioequivalence; rifampicin

Additional relevant MeSH terms:

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Rifampin; Isoniazid; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents; Leprostatic Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Fatty Acid Synthesis Inhibitors; Hypolipidemic Agents; Antimetabolites; Lipid Regulating Agents