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CompletedNCT01399788Updated Apr 5, 2017Results posted

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

A Phase 1 interventional study of Myrin P Forte and Single drug references in Healthy Volunteers, sponsored by Pfizer. Completed at 1 site in Singapore. Open to participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-04-05.

Sponsored by Pfizer · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
36
Allocation
Randomized
Ages
21 Years to 55 Years
Sex
All
01

Study summary

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

02

Conditions studied

  • Healthy Volunteers

Keywords

  • Bioequivalence
  • Healthy Volunteers
03

In context

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • Active comparator
    1.0

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

    Drug: Myrin P Forte

  • Active comparator
    2.0

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

    Drug: Single drug references

Interventions

  • DrugMyrin P Forte

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

  • DrugSingle drug references

    containing Rifampicin, Isoniazid, Ethambutol and Pyrazinamide as single agents

06

What researchers measure

Primary outcomes

  1. 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).

    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

  2. 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

  3. 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.

    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

  4. 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.

    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

Secondary outcomes

  1. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞])

    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-∞).

    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

  2. Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide

    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 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

  3. Plasma Decay Half-life (t1/2)

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

    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

  4. 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

07

Results

Posted Mar 16, 2012

Participant flow

First Intervention Period
Participant flow — First Intervention Period
MilestoneMyrin-P Forte First, Then Four Single Drug ReferencesFour Single Drug References First, Then Myrin-P Forte
Started1818
Completed1718
Not completed10
Withdrew: Adverse event10
Washout Period (at Least 1 Week)
Participant flow — Washout Period (at Least 1 Week)
MilestoneMyrin-P Forte First, Then Four Single Drug ReferencesFour Single Drug References First, Then Myrin-P Forte
Started1718
Completed1718
Not completed00
Second Intervention Period
Participant flow — Second Intervention Period
MilestoneMyrin-P Forte First, Then Four Single Drug ReferencesFour Single Drug References First, Then Myrin-P Forte
Started1718
Completed1718
Not completed00

Outcome measures

PrimaryArea 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).

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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
ng*hr/mLMyrin-P ForteFour Single Drug References
Rifampicin79360.0 ± 29613.077180.0 ± 20516.0
Isoniazid20550.0 ± 12920.018800.0 ± 12941.0
Ethambutol15070.0 ± 3298.815170.0 ± 3119.1
Statistical analysis
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 103.81 · 90% CI 99.20 to 108.64
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 107.28 · 90% CI 101.95 to 112.90
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 99.48 · 90% CI 94.92 to 104.25
PrimaryMaximum 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
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax)
ng/mLMyrin-P ForteFour Single Drug References
Rifampicin12120.0 ± 3682.311830.0 ± 2351.8
Isoniazid4418.0 ± 1619.04237.0 ± 1658.9
Ethambutol2771.0 ± 825.42865.0 ± 950.5
Statistical analysis
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 102.75 · 90% CI 95.36 to 110.71
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 103.85 · 90% CI 92.13 to 117.07
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 99.48 · 90% CI 94.92 to 104.25
PrimaryDose 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.

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
Reported as:
Geometric mean · (ng*hr/mL)/mg
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide
(ng*hr/mL)/mgMyrin-P ForteFour Single Drug References
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) for Pyrazinamide453500 ± 76250447900 ± 82578
Statistical analysis
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 101.73 · 90% CI 99.12 to 104.40
PrimaryDose 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.

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
Reported as:
Geometric mean · (ng/mL)/mg
Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide
(ng/mL)/mgMyrin-P ForteFour Single Drug References
Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) for Pyrazinamide33890.0 ± 6490.235580.0 ± 12134.0
Statistical analysis
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 95.17 · 90% CI 88.60 to 102.22
SecondaryArea Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞])

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-∞).

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
Reported as:
Geometric mean · ng*hr/mL
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC[0-∞])
ng*hr/mLMyrin-P ForteFour Single Drug References
Rifampicin (n= 36, 35)80940.0 ± 34613.078400.0 ± 22226.0
Isoniazid (n= 35, 35)21210.0 ± 13562.019460.0 ± 14171.0
Ethambutol (n= 28, 31)17150.0 ± 3362.117050.0 ± 3378.9
Statistical analysis
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 104.30 · 90% CI 99.70 to 109.10
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 105.74 · 90% CI 100.32 to 111.46
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 100.97 · 90% CI 96.28 to 105.88
SecondaryDose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide

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 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
Reported as:
Geometric mean · (ng*hr/mL)/mg
Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide
(ng*hr/mL)/mgMyrin-P ForteFour Single Drug References
Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0-∞][dn]) for Pyrazinamide471000 ± 85153464800 ± 92222
Statistical analysis
  • Myrin-P Forte vs Four Single Drug References · Ratio of adjusted means: 101.80 · 90% CI 99.24 to 104.43
SecondaryPlasma Decay Half-life (t1/2)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

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
Reported as:
Mean · hr
Plasma Decay Half-life (t1/2)
hrMyrin-P ForteFour Single Drug References
Rifampicin (n= 36, 35)3.6630 ± 1.04773.4290 ± 0.6938
Isoniazid (n= 35, 35)3.7340 ± 0.91973.9470 ± 1.1751
Ethambutol (n= 28, 31)7.7430 ± 1.17167.6390 ± 1.1158
Pyrazinamide (n= 36, 35)9.8630 ± 1.33339.7660 ± 1.3671
SecondaryTime 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
Reported as:
Median · hr
Time to Reach Maximum Observed Plasma Concentration (Tmax)
hrMyrin-P ForteFour Single Drug References
Rifampicin2.00 (1.00 to 4.00)1.50 (1.00 to 3.00)
Isoniazid1.02 (0.25 to 2.52)1.00 (0.25 to 3.00)
Ethambutol2.77 (1.00 to 4.28)2.48 (1.50 to 4.00)
Pyrazinamide1.50 (0.25 to 3.02)1.50 (0.25 to 6.00)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Myrin-P Forte—0/36 (0%)34/36 (94.4%)
Four Single Drug References—0/35 (0%)31/35 (88.6%)
Most frequent other events
Showing 10 of 16
Most frequent other events
EventMyrin-P ForteFour Single Drug References
ChromaturiaRenal and urinary disorders32/3631/35
Blood glucose increasedInvestigations1/361/35
Cardiac murmur functionalInvestigations0/361/35
DizzinessNervous system disorders0/361/35
Oropharyngeal painRespiratory, thoracic and mediastinal disorders0/361/35
Dermatitis contactSkin and subcutaneous tissue disorders1/361/35
Drug eruptionSkin and subcutaneous tissue disorders1/361/35
Abdominal painGastrointestinal disorders1/360/35
DiarrhoeaGastrointestinal disorders1/360/35
NauseaGastrointestinal disorders1/360/35

Baseline characteristics

Age, Continuous
Age, Continuous(years)Entire Study Population
Mean32.6 ± 8.8
Sex: Female, Male
Sex: Female, Male(Participants)Entire Study Population
Female2
Male34
08

Study locations

1 site
  • Pfizer Investigational Site
    Singapore, 188770, Singapore
09

References and documents

Publications

  • 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. PubMed 24200275 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 5, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01399788
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Jul 22, 2011
Start date
Jul 2011
Primary completion
Aug 2011
Completion
Aug 2011
Results posted
Mar 16, 2012
Last update
Apr 5, 2017

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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