Pravastatin 80 mg Tablets Dosed in Healthy Subjects Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00829309
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

This study compared the relative bioavailability (rate and extent of absorption) of Pravastatin Sodium Tablets 80 mg by Teva Pharmaceutical Industries, Ltd. with that of Pravachol® Tablets 80 mg by Bristol-Myers Squibb Company following a single oral dose (1 x 80 mg tablet)in healthy adult male subjects administered under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Pravastatin; Drug: Pravastatin	Phase 1

Detailed Description

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Outcome: Confidence interval fell within 80-125% therefore met the FDA Bioequivalence criteria; no drug related, serious, unexpected adverse events were reported during the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 80 mg Pravastatin Sodium Tablets Under Non-Fasting Conditions
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Mar 1, 2005
• Actual Study Completion Date: Mar 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pravastatin Pravastatin 80 mg Tablet (test) dosed in first period followed by Pravachol® 80 mg Tablet (reference) dosed in second period	Drug: Pravastatin; 80 mg Tablet
Active Comparator: Pravachol® Pravachol® 80 mg Tablet (reference) dosed in first period followed by Pravastatin 80 mg Tablet (test) dosed in second period	Drug: Pravastatin; 80 mg Tablets; Other Names: Pravachol® 80 mg Tablets

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration - Pravastatin in Plasma [Blood samples collected over 16 hour period]

   Bioequivalence based on Cmax

2. AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) [Blood samples collected over 16 hour period]

   Bioequivalence based on AUC0-inf

3. AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) [Blood samples collected over 16 hour period]

   Bioequivalence based on AUC0-t

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria

• Screening Demographics: All subjects selected for this study will be healthy men 18 years of age or older at the time of dosing.

• The subject's body mass index (BMI) should be less than or equal to 30.

• Screening Procedures: Each subject will complete the screening process within 28 days prior to period I dosing.

• Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed and signed by each potential participant before full implementation of screening procedures.

• Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature.

• The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems.

• The screening clinical laboratory procedures will include:

• HEMATOLOGY: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count

• CLINICAL CHEMISTRY: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase

• HIV antibody, hepatitis GB surface antigen, hepatitis C antibody screens

• URINALYSIS: by dipstick; full microscopic examination if dipstick positive

• URINE DRUG SCREEN: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine

Exclusion Criteria

• Subjects with a recent history of drug or alcohol addiction or abuse.

• Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators).

• Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant.

• Subjects demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody or HIV antibody.

• Subjects demonstrating a positive drug abuse screen when screened for this study.

• Subjects with a history of allergic response(s) to pravastatin or related drugs.

• Subjects with a history of clinically significant allergies including drug allergies.

• Subjects with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators).

• Subjects who currently or report using tobacco products within 90 days of Period I dose administration.

• Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing.

• Subjects who report donating greater than 150 mL of blood within 28 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study.

• Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to Period I dosing. All subjects will be advised not to donate plasma for four weeks after completing the study.

• Subjects who report receiving any investigational drug within 28 days prior to Period I dosing.

• Subjects who report taking any systemic prescription medication in the 14 days prior to Period I dosing.

• Subjects who report an intolerance of direct venipuncture.

• Subjects who report consuming an abnormal diet during the 28 days prior to Period I dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute, Ltd.	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: James D Carlson, Pharm D, PRACS Institute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00829309
• Other Study ID Numbers: R05-0202
• First Posted: Jan 27, 2009
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Pravastatin

Study Results

Participant Flow

Arm/Group Title	Pravastatin (Test) First	Pravachol® (Reference) First
Arm/Group Description	Pravastatin 80 mg Tablet (test) dosed in first period followed by Pravachol® 80 mg Tablet (reference) dosed in second period	Pravachol® 80 mg Tablet (reference) dosed in first period followed by Pravastatin 80 mg Tablet (test) dosed in second period
Period Title: First Intervention
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	8	8
COMPLETED	7	8
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	7	8
COMPLETED	7	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pravastatin (Test) First	Pravachol® (Reference) First	Total
Arm/Group Description	Pravastatin 80 mg Tablet (test) dosed in first period followed by Pravachol® 80 mg Tablet (reference) dosed in second period	Pravachol® 80 mg Tablet (reference) dosed in first period followed by Pravastatin 80 mg Tablet (test) dosed in second period	Total of all reporting groups
Overall Participants	8	8	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	16 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	8 100%	16 100%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	8 100%	6 75%	14 87.5%
Hispanic	0 0%	1 12.5%	1 6.3%
Black	0 0%	1 12.5%	1 6.3%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration - Pravastatin in Plasma
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 16 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Pravastatin	Pravachol®
Arm/Group Description	Pravastatin 80 mg Tablet (test) dosed in either period	Pravachol® 80 mg Tablet (reference) dosed in either period
Measure Participants	15	15
Mean (Standard Deviation) [ng/mL]	126.69 (60.95)	130.64 (58.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin, Pravachol®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	98.45
	Confidence Interval	() 90%; 80.08 to 121.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

2. Primary Outcome

Title	AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 16 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis. Data from one subject could not be included in the AUC0-inf calculation for Pravachol®.

Arm/Group Title	Pravastatin	Pravachol®
Arm/Group Description	Pravastatin 80 mg Tablet (test) dosed in either period	Pravachol® 80 mg Tablet (reference) dosed in either period
Measure Participants	15	14
Mean (Standard Deviation) [ng*h/mL]	273.32 (116.86)	299.56 (121.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin, Pravachol®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	90.98
	Confidence Interval	() 90%; 85.23 to 97.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

3. Primary Outcome

Title	AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 16 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Pravastatin	Pravachol®
Arm/Group Description	Pravastatin 80 mg Tablet (test) dosed in either period	Pravachol® 80 mg Tablet (reference) dosed in either period
Measure Participants	15	15
Mean (Standard Deviation) [ng*h/mL]	241.29 (104.11)	251.86 (111.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pravastatin, Pravachol®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	96.30
	Confidence Interval	() 90%; 85.34 to 108.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal Investigator is not permitted to discuss or publish trial results.