Cilostazol 50 mg Tablets Under Fasting Conditions

A Relative Bioavailability Study of 50 mg Cilostazol Tablets Under Fasting Conditions

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Cilostazol 50 mg Tablets; Drug: Pletal®

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • East Grand Forks, Minnesota, United States, 56721
      • PRACS Institute Ltd.
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • PRACS Institute, Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Observed Concentration	Bioequivalence based on Cmax	Blood samples collected over 72 hour period
AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)	Bioequivalence based on AUC0-inf	Blood samples collected over 72 hour period
AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration	Bioequivalence based on AUC0-t	Blood samples collected over 72 hour period

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): February 1, 2004
• Study Completion (Actual): February 1, 2004

Study Registration Dates

• First Submitted: February 6, 2009
• First Submitted That Met QC Criteria: February 9, 2009
• First Posted (Estimate): February 10, 2009

Study Record Updates

• Last Update Posted (Estimate): September 11, 2009
• Last Update Submitted That Met QC Criteria: September 1, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: R04-099