Fasted Bioavailability Study of Cilostazol Tablets, 100 mg

• Sponsor: Mutual Pharmaceutical Company, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00684762
• Collaborator: (none)
• Enrollment: 32
• Arms: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate and compare the relative bioavailability of a test formulation of cilostazol tablets to an equivalent dose of Pletal® (cilostazol) tablets after a single oral dose administered under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Therapeutic Equivalency	Drug: Cilostazol 100 mg Tablets; Drug: Cilostazol (Pletal®) 100 mg Tablets	Phase 1

Detailed Description

The purpose of this study is to evaluate and compare the relative bioavailability of a test formulation of cilostazol tablets to an equivalent dose of Pletal® (cilostazol) tablets after a single oral dose administered under fasting conditions. Thirty-two non-smoking, non-obese, healthy male and female volunteers between the ages of 18 and 55 will be randomly assigned in a crossover fashion to receive each of two cilostazol dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, after an overnight fast of at least 10 hours, subjects will receive either a single oral dose of the test formulation, cilostazol (1 x 100 mg tablet), or a single oral dose of the reference formulation, Pletal® (1 x 100 mg tablet). After a 7 day washout period on the morning of Day 8, following an overnight fast of at least 10 hours, subjects will receive the alternate regimen. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of cilostazol. Blood sampling will then continue on a non-confined basis at 36 and 48 hours post-dose. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drug and/or procedures. Blood pressure and pulse will be measured before dosing and at 3 and 24 hours post-dose. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Comparative Bioavailability Study of Cilostazol Tablets, 100mg Under Fasting Conditions
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Mar 1, 2004
• Actual Study Completion Date: Mar 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cilostazol A single dose of cilostazol (1 x 100 mg tablet) administered after an overnight fast of at least 10 hours.	Drug: Cilostazol 100 mg Tablets; Cilostazol (1 x 100 mg tablet) administered after an overnight fast of at least 10 hours
Experimental: Pletal® (cilostazol) A single dose of cilostazol (Pletal® 1 x 100 mg tablet) administered after an overnight fast of at least 10 hours.	Drug: Cilostazol (Pletal®) 100 mg Tablets; Cilostazol (Pletal® 1 x 100mg tablet) administered after an overnight fast of at least 10 hours.; Other Names: Pletal®

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) [serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose.]

   The maximum or peak concentration that cilostazol (test and reference product) reaches in the plasma.

2. Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] [serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose.]

   The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable cilostazol (test and reference) concentration (t), as calculated by the linear trapezoidal rule.

3. Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)] [serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose.]

   The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable cilostazol (reference and test) plasma concentration to the elimination rate constant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy adults 18-55 years of age

• Non-smoking

• Non-pregnant (post-menopausal, surgically sterile or using effective contraceptive measures)

• No more than 15% plus or minus from ideal weight for subject's height and elbow breadth as defined by the Metropolitan Life Insurance Company Statistical Bulletin. Extrapolations, if required, to be conducted according to BASi Standard Operating Procedures

• Medically healthy on the basis of medical history and physical examination within 30 days prior to the start of the study

• Test results from blood chemistry, hematology, and urinalysis performed within 30days prior to the start of the study within clinically acceptable limits

• At screening, subjects must have blood pressure and pulse rate within the following ranges: Systolic blood pressure 90-140mmHg; Diastolic blood pressure 50-90mmHg; Pulse 45-100 bpm

• An acceptable electrocardiogram (EKG): sinus rhythm with no evidence of AV block or ischemic changes

Exclusion Criteria:

• Prescription drug use (excluding hormonal contraceptives) within 14 days prior to drug administration, each period

• Aspirin ingestion within 7 days prior to drug administration, each period

• Use of any over-the-counter preparations, herbal remedies, and/or nutritional supplements within 7 days prior to drug administration, each period

• Consumption of grapefruit juice or grapefruit-containing products within 72 hours prior to drug administration , each period

• Consumption of alcohol within 24 hours prior to drug administration, each period

• Consumption of caffeine within 10 hours prior to drug administration, each period

• Female subjects must not be pregnant or nursing; and must be surgically sterile; one year post-menopausal; or on hormonal contraceptive agent(s), a diaphragm or condom with spermicidal foam or jelly, or IUD for at least three months prior to drug administration and agree to use the same method of contraception for at least 1 month after the last drug administration

• Subjects with a history or presence of significant organ system (cardiovascular, neurological, hepatic, hematopoietic, renal, pulmonary, endocrine, or gastrointestinal) disorders, or ongoing infectious diseases

• History of hypersensitivity or adverse reactions to cilostazol (Pletal®), or other related drugs

• Recent (12 month) history or evidence of alcoholism or drug abuse

• Positive results to Human Immunodeficiency Virus (HIV) or Hepatitis B surface Antigen (HBsAg) tests

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Mutual Pharmaceutical Company, Inc.

Investigators

• Principal Investigator: Dilip K Guha-Ray, M.D., BASi Baltimore Clinical Research Unit

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Recalls, Market Withdrawals and Safety Alerts
• Daily Med - Posting of Recently Submitted Labeling to the FDA
• URL Pharma Generic Division

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00684762
• Other Study ID Numbers: 11788
• First Posted: May 28, 2008
• Last Update Posted: Dec 22, 2009
• Last Verified: Nov 1, 2009

• Additional relevant MeSH terms: Cilostazol

Study Results

Participant Flow

Arm/Group Title	Cilostazol 100 mg Tablets Then Pletal® 100 mg Tablets	Pletal® 100 mg Tablets Then Cilostazol 100 mg Tablets
Arm/Group Description	On the morning of Day 1 subjects received one tablet of the test formulation, Cilostazol 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received one tablet of the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours.	On the morning of Day 1 subjects received one tablet of the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received one tablet of the test formulation, Cilostazol 100 mg, after an overnight fast of at least 10 hours.
Period Title: First Intervention
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	16
COMPLETED	14	14
NOT COMPLETED	2	2
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cilostazol 100 mg Tablets and Pletal® 100 mg Tablets
Arm/Group Description	All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 8, each subject received one tablet of either Cilostazol 100 mg or Pletal® 100 mg following an overnight fast of at least 10 hours.
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	32 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.09 (11.63)
Sex: Female, Male (Count of Participants)
Female	4 12.5%
Male	28 87.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 6.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	21 65.6%
White	8 25%
More than one race	0 0%
Unknown or Not Reported	1 3.1%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax)
Description	The maximum or peak concentration that cilostazol (test and reference product) reaches in the plasma.
Time Frame	serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

Plasma concentration data for 28 of the 32 enrolled participants were used in the statistical analysis. Four subjects did not complete the study and none of their collected data was used.

Arm/Group Title	Cilostazol 100 mg Tablets	Pletal® 100 mg Tablets
Arm/Group Description	On the morning of Day 1 subjects received one tablet of either the test formulation, cilostazol 100mg, or the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received the alternate regimen following an overnight fast of at least 10 hours.	On the morning of Day 1 subjects received one tablet of the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received one tablet of the test formulation, Cilostazol 100 mg, after an overnight fast of at least 10 hours.
Measure Participants	28	28
Mean (Standard Deviation) [ng/mL]	484.895 (205.181)	472.689 (140.843)

2. Primary Outcome

Title	Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]
Description	The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable cilostazol (test and reference) concentration (t), as calculated by the linear trapezoidal rule.
Time Frame	serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

Plasma concentration data for 28 of the 32 enrolled participants were used in the statistical analysis. Four subjects did not complete the study and none of their collected data was used.

Arm/Group Title	Cilostazol 100 mg Tablets	Pletal® 100 mg Tablets
Arm/Group Description	On the morning of Day 1 subjects received one tablet of either the test formulation, cilostazol 100mg, or the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received the alternate regimen following an overnight fast of at least 10 hours.	On the morning of Day 1 subjects received one tablet of the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received one tablet of the test formulation, Cilostazol 100 mg, after an overnight fast of at least 10 hours.
Measure Participants	28	28
Mean (Standard Deviation) [ng-hr/mL]	6,518.90 (1,600.14)	6,711.57 (1,895.25)

3. Primary Outcome

Title	Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]
Description	The area under the plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable cilostazol (reference and test) plasma concentration to the elimination rate constant.
Time Frame	serial pharmacokinetic concentrations were drawn pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours post-dose.

Outcome Measure Data

Analysis Population Description

Plasma concentration data for 26 of the 32 enrolled participants were used in the statistical analysis. Four subjects did not complete the study and none of their collected data was used. Additionally, two subjects had data values that were not used in this analysis.

Arm/Group Title	Cilostazol 100 mg Tablets	Pletal® 100 mg Tablets
Arm/Group Description	On the morning of Day 1 subjects received one tablet of either the test formulation, cilostazol 100mg, or the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received the alternate regimen following an overnight fast of at least 10 hours.	On the morning of Day 1 subjects received one tablet of the reference formulation, Pletal® 100 mg, after an overnight fast of at least 10 hours, followed by a 7 day washout period. On the morning of Day 8 subjects received one tablet of the test formulation, Cilostazol 100 mg, after an overnight fast of at least 10 hours.
Measure Participants	26	26
Mean (Standard Deviation) [ng-hr/mL]	7,224.99 (1,786.61)	7,650.45 (2,294.39)

Adverse Events

Adverse Event Reporting Description	32 subjects were enrolled in this study. Several subjects dropped out of the study prior to receiving both interventions. 30 subjects were administered cilostazol 100 mg tablets and 30 subjects were administered Pletal® 100 mg tablets.
Arm/Group Title	Cilostazol 100 mg Tablets		Pletal® 100 mg Tablets
Arm/Group Description	All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 8, each subject received one tablet of either cilostazol 100 mg or Pletal® 100 mg following an overnight fast of at least 10 hours.		All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 8, each subject received one tablet of either cilostazol 100 mg or Pletal® 100 mg following an overnight fast of at least 10 hours.
All Cause Mortality
	Cilostazol 100 mg Tablets		Pletal® 100 mg Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cilostazol 100 mg Tablets		Pletal® 100 mg Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Cilostazol 100 mg Tablets		Pletal® 100 mg Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)		12/30 (40%)
Blood and lymphatic system disorders
Lymphadeno	1/30 (3.3%)	1	0/30 (0%)	0
Injury, poisoning and procedural complications
Pain	0/30 (0%)	0	1/30 (3.3%)	1
Paresthesia	1/30 (3.3%)	1	0/30 (0%)	0
Investigations
Eosinophilia	0/30 (0%)	0	1/30 (3.3%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/30 (3.3%)	1	0/30 (0%)	0
LDH increased	1/30 (3.3%)	1	0/30 (0%)	0
SGOT increased	1/30 (3.3%)	1	0/30 (0%)	0
Nervous system disorders
Headache	6/30 (20%)	6	6/30 (20%)	6
Renal and urinary disorders
Urine abnormal	0/30 (0%)	0	3/30 (10%)	3
Respiratory, thoracic and mediastinal disorders
Rhinitis	0/30 (0%)	0	1/30 (3.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.