Cilostazol 50 mg Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00839930
• Collaborator: (none)
• Enrollment: 30
• Locations: 2
• Arms: 2
• Patients Per Site: 15

Study Details

Study Description

Brief Summary

This study will compare the relative bioavailability (rate and extent of absorption) of 50 mg Cilostazol Tablets manufactured by TEVA Pharmaceuticals Industries Ltd. and distributed by TEVA Pharmaceuticals USA with that of PLETAL Tablets manufactured by Otsuka Pharmaceuticals Co., Ltd. for Otsuka America Pharmaceutical, Inc. following a single oral dose (1 x 50 mg tablet) in healthy adult subjects administered under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Cilostazol 50 mg Tablets; Drug: Pletal®	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of 50 mg Cilostazol Tablets Under Fasting Conditions
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Feb 1, 2004
• Actual Study Completion Date: Feb 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cilostazol (test) Cilostazol 50 mg Tablet (test) dosed in first period followed by Pletal® 50 mg Tablet (reference) dosed in second period	Drug: Cilostazol 50 mg Tablets; 1 x 50 mg, single-dose fasting
Active Comparator: Pletal® (reference) Pletal® 50 mg Tablet (reference) dosed in first period followed by Cilostazol 50 mg Tablet (test) dosed in second period.	Drug: Pletal®; 1 x 50 mg, single-dose tablet

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 72 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 72 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 [Blood samples collected over 72 hour period]

   Bioequivalence based on AUC0-t

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Screening Demographics: All volunteers selected for this study will be healthy men or women 18 years of age or older at the time of dosing. The volunteer's body mass index (BMI) is less than or equal to 30.

• Screening Procedures: Each volunteer 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, RBC count, WBC count with differential, platelet count;

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

• HIV antibody and hepatitis B surface antigen and hepatitis C antibody screens;

• Urinalysis: by dipstick; full microscopic examination if dipstick positive; and

• Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, and phencyclidine;

• Serum Pregnancy Screen (female volunteers only).

• Follicle Stimulating Hormone (FSH; female subjects only): verify postmenopausal status

• If female and:

• is postmenopausal for at least 1 year with postmenopausal status defined as: > 60 years of age and amenorrheic for at least one year; if 60 years of age or younger, must also have a serum FSH level >30 IU/L; or

• is surgically sterile for at least 6 months (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).

Exclusion Criteria:

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

• Volunteers 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).

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

• Volunteers demonstrating a positive hepatitis B surface antigen screen or a reactive HIV antibody screen.

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

• Female volunteers demonstrating a positive pregnancy screen.

• Female volunteers who are currently breastfeeding.

• Volunteers with a history of allergic response(s) to cilostazol or related drugs.

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

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

• Volunteers who are currently using or report using tobacco products within 90 days prior to Period I dosing.

• Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to Period I dosing.

• Volunteers who report donating greater than 150 mL of blood within 30 days prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study.

• Volunteers 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.

• Volunteers who report receiving any investigational drug within 30 days prior to Period I dosing.

• Volunteers who report taking any prescription medication or nonprescription medication in the 14 days or 7 days, respectively, prior to Period I dosing with the exception of topical products without systemic absorption.

• Volunteers who have been on an abnormal diet during the 28 days prior to Period I dosing.

• Volunteers who report an intolerance or direct venipuncture.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute Ltd.	East Grand Forks	Minnesota	United States	56721
2	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: NCT00839930
• Other Study ID Numbers: R04-099
• First Posted: Feb 10, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Cilostazol (Test) First	Pletal® (Reference) First
Arm/Group Description	Cilostazol 50 mg Tablets (test)dosed in first period followed by Pletal® 50 mg Tablets (reference) dosed in second period	Pletal® 50 mg Tablets (reference) dosed in first period followed by Cilostazol 50 mg Tablets (test) dosed in second period
Period Title: First Intervention
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cilostazol (Test) First	Pletal® (Reference) First	Total
Arm/Group Description	Cilostazol 50 mg Tablets (test)dosed in first period followed by Pletal® 50 mg Tablets (reference) dosed in second period	Pletal® 50 mg Tablets (reference) dosed in first period followed by Cilostazol 50 mg Tablets (test) dosed in second period	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	15 100%	30 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	6 40%	6 20%
Male	15 100%	9 60%	24 80%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	15 100%	14 93.3%	29 96.7%
Asian	0 0%	1 6.7%	1 3.3%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 72 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	Cilostazol	Pletal®
Arm/Group Description	Cilostazol 50 mg Tablets (test)dosed in either period	Pletal® 50 mg Tablets (reference) dosed in either period
Measure Participants	30	30
Mean (Standard Deviation) [ng/mL]	376.46 (115.88)	398.06 (108.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cilostazol, Pletal®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of Variance (ANOVA) will be performed on the log-transformed AUC0-t, AUC0-inf and Cmax parameters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	93.39
	Confidence Interval	() 90%; 87.33 to 99.86
	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 72 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	Cilostazol	Pletal®
Arm/Group Description	Cilostazol 50 mg Tablets (test)dosed in either period	Pletal® 50 mg Tablets (reference) dosed in either period
Measure Participants	30	30
Mean (Standard Deviation) [ng*h/mL]	5010.17 (1508.03)	5176.83 (1435.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cilostazol, Pletal®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of Variance (ANOVA) will be performed on the log-transformed AUC0-t, AUC0-inf and Cmax parameters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	96.14
	Confidence Interval	() 90%; 91.04 to 101.52
	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
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 72 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	Cilostazol	Pletal®
Arm/Group Description	Cilostazol 50 mg Tablets (test)dosed in either period	Pletal® 50 mg Tablets (reference) dosed in either period
Measure Participants	30	30
Mean (Standard Deviation) [ng*h/mL]	4618.70 (1416.60)	4745.22 (1370.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cilostazol, Pletal®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of Variance (ANOVA) will be performed on log-transformed AUC0-t, AUC0-inf and Cmax parameters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	96.64
	Confidence Interval	() 90%; 92.13 to 101.37
	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.