Cilostazol 100 mg Tablet Formulations Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00838630
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

The objective of this randomized, single-dose, two-way evaluation is to compare the bioequivalence of a test cilostazol formulation to an equivalent oral dose of the commercially available cilostazol in a test population of 36 adult subjects under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Cilostazol 100 mg tablets; Drug: Pletal® 100 mg tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Randomized, Two-Way, Single-Dose, Open-Label Study to Evaluate the Bioequivalence of a Test Tablet Formulation of Cilostazol, 100 mg, Compared to an Equivalent Dose of a Commercially Available Reference Drug Product in 36 Fasted, Healthy, Adult Subjects
• Study Start Date: Nov 1, 2003
• Actual Primary Completion Date: Nov 1, 2003
• Actual Study Completion Date: Nov 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Cilostazol 100 mg tablets; 1 x 100 mg
Active Comparator: 2	Drug: Pletal® 100 mg tablets; 1 x 100 mg

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 96 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 96 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 96 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:

• Sex: Male and Female; similar proportion of each preferred. Female subjects must be surgically sterile for at least six (6) months or postmenopausal for at least one (1) year.

• Age: At least 18 years.

• Weight: Body Mass Index (BMI) of 30 or less.

• Qualifying subjects must be in good health and physical condition as determined by medical history, complete physical examination, and laboratory test, all obtained within four (4) weeks prior to study start. The subject may not have a history of significant past illness expected to affect the investigation. The normal status of subjects will be confirmed by the following procedures:

• Laboratory Tests:

Hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Na, K, Cl), fasting blood glucose, BUN, bilirubin, creatinine, AST, ALT, LD, alkaline phosphatase, and urinalysis. HIV, Hepatitis B, Hepatitis C, and drugs of abuse testing will be done for screening purposes only. Urine drugs of abuse testing will be repeated at each check-in. Female subjects will have a serum pregnancy test done at screening and a urine pregnancy test prior to each study period at check-in.

Laboratory values which are greater than 20% of the normal range will not qualify unless specifically accepted (with comment) by the Principal Investigator. Results of HIV, Hepatitis B, Hepatitis C, and drugs of abuse must be negative or non-reactive for the subject to qualify for the study.

• Electrocardiogram A 12-lead electrocardiogram (ECG) will be obtained for all subjects. The original tracings, plus interpretation, will be included in the case report form packet.

• Subjects must read and sign the Consent Form.

Exclusion Criteria:

• History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months.

• History of sensitivity to cilostazol, quinolones, or any antiplatelet drug.

• History of malignancy, stroke, diabetes, cardiac, renal or liver disease or other serious illness.

• History of GERD (gastroesophageal reflux disease), malabsorption syndrome, colon cancer, or chronic colitis, including Crohn's disease.

• History of treatment for pulmonary obstruction or asthma within the past five (5) years.

• History of severe headaches or migraines.

• History of glaucoma.

• History of chronic infectious disease.

• History of psychiatric disorder.

• History of thyroid disorder/disease.

• History of hypertension.

• Females who are capable of becoming pregnant or are lactating.

• Inability to read and/or sign the consent form.

• Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study.

• Subjects who have donated blood within four (4) weeks prior to the initial dosing for this study.

• Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.). Three months abstinence is required.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research Inc.	St. Charles	Missouri	United States	63301

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Steven Herrmann, M.D., Ph. D., Cetero Research, San Antonio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00838630
• Other Study ID Numbers: 03261
• First Posted: Feb 6, 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 100 mg Tablets (test) dosed in first period followed by Pletal® 100 mg Tablets (reference) dosed in second period.	Pletal® 100 mg Tablets (reference) dosed in first period followed by Cilostazol 100 mg Tablets (test) dosed in second period
Period Title: First Intervention
STARTED	18	18
COMPLETED	17	18
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	17	18
COMPLETED	16	18
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	16	18
COMPLETED	16	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cilostazol (Test) First	Pletal® (Reference) First	Total
Arm/Group Description	Cilostazol 100 mg Tablets (test) dosed in first period followed by Pletal® 100 mg Tablets (reference) dosed in second period.	Pletal® 100 mg Tablets (reference) dosed in first period followed by Cilostazol 100 mg Tablets (test) dosed in second period	Total of all reporting groups
Overall Participants	18	18	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	18 100%	36 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 11.1%	3 16.7%	5 13.9%
Male	16 88.9%	15 83.3%	31 86.1%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	17 94.4%	15 83.3%	32 88.9%
Black	1 5.6%	3 16.7%	4 11.1%
Region of Enrollment (participants) [Number]
United States	18 100%	18 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 96 hour period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cilostazol	Pletal®
Arm/Group Description	Cilostazol 100 mg Tablets (test) dosed in either period	Pletal® 100 mg Tablets (reference) dosed in either period
Measure Participants	34	34
Mean (Standard Deviation) [ng/mL]	536 (147)	543 (145)

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 for 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	98.27
	Confidence Interval	() 90%; 92.32 to 104.61
	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 96 hour period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cilostazol	Pletal®
Arm/Group Description	Cilostazol 100 mg Tablets (test) dosed in either period	Pletal® 100 mg Tablets (reference) dosed in either period
Measure Participants	34	34
Mean (Standard Deviation) [ng*h/mL]	8670 (3626)	8974 (3147)

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 for 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	94.37
	Confidence Interval	() 90%; 90.47 to 98.43
	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 96 hour period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cilostazol	Pletal®
Arm/Group Description	Cilostazol 100 mg Tablets (test) dosed in either period	Pletal® 100 mg Tablets (reference) dosed in either period
Measure Participants	34	34
Mean (Standard Deviation) [ng*h/mL]	8430 (3507)	8634 (3104)

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	95.70
	Confidence Interval	() 90%; 91.52 to 100.08
	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.