A Bioequivalence Study Comparing A Fixed Dose Combination... | NCT01399788

NCT01399788

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Myrin P Forte	Drug	Tablet containing Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, given once daily, single dose	1.0

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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-∞).	0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Singapore		188770	Singapore

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24200275	Derived	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.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Myrin-P Forte First, Then Four Single Drug References	Single oral dose of 4 fixed dose combination (FDC) tablets of Myrin-P Forte (each tablet contains 150 milligram (mg) rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide) in first intervention period; and single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in second intervention period. A washout period of at least 1 week was maintained between each period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

FG00018 subjects
FG00118 subjects

Type of Units Analyzed

ID	Title	Description
BG000	Entire Study Population	Includes participants randomized to receive Myrin-P Forte first and four single drug references first.

Units	Counts
Participants	BG00036

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Rifampicin

Title	Measurements
	OG00079360.0± 29613.0 OG00177180.0± 20516.0

Isoniazid

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Rifampicin; 32 participants (16 per sequence) provided at least 99% power that 90% confidence interval (CI) for ratio of test to reference for AUClast lie within acceptance region of 80% - 125%. An intra-subject coefficient of variation (CV) estimate of approximately 14.5% for AUClast was used for this power calculation. Natural log transformed AUClast was analyzed using mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.					Ratio of Adjusted Means	103.81			2-Sided	90	99.20	108.64					Superiority or Other

Primary

Maximum Observed Plasma Concentration (Cmax)

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

ng/mL

0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Units	Counts
Participants	OG000

Primary

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.

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

(ng*hr/mL)/mg

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

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Primary

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.

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

(ng/mL)/mg

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

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Units	Counts

Secondary

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-∞).

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period. Here, 'n' is number of participants who were evaluable for this measure.

Posted

Geometric Mean

Standard Deviation

ng*hr/mL

0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16 and 24 hrs post-dose

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Units	Counts

Secondary

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.

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

(ng*hr/mL)/mg

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

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Secondary

Plasma Decay Half-life (t1/2)

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

Posted

Mean

Standard Deviation

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

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Units	Counts

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax)

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters for one of four analytes in at least 1 treatment period.

Posted

Median

Full Range

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

ID	Title	Description
OG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.
OG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Myrin-P Forte	Single oral dose of 4 FDC tablets of Myrin-P Forte (Test) in either first intervention period or second intervention period. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 275 mg ethambutol and 400 mg pyrazinamide.			0	36	34	36
EG001	Four Single Drug References	Single oral dose of 4 reference products: 600 mg rifampicin capsules, 300 mg isoniazid, 1100 mg ethambutol and 1500 mg pyrazinamide tablets in either first intervention period or second intervention period.			0	35	31	35

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Catheter site swelling	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Pyrexia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Oral herpes	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Blood glucose increased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected35 at risk
Cardiac murmur functional	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected35 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected35 at risk
Headache	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Chromaturia	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG00032 affected36 at risk EG00131 affected35 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected35 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected35 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected35 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected35 at risk

OG00118800.0± 12941.0

Units	Counts
Participants	OG00036 OG00135

Units	Counts
Participants	OG00036 OG00135