BE Study of Once Daily PMR Compared to Twice Daily Cilostazol IR Tablets in Healthy Volunteers

An Open-Label, Randomized, Two-Treatment, Two-Sequence, Four-Period, Fully Replicated Crossover Bioequivalence Study of Once Daily PMR Compared to Twice Daily Cilostazol IR Tablets in Healthy Volunteers

The study is designed to evaluate the bioequivalence and the within-subject variability between the test formulation of extended-release tablet of cilostazol (PMR) administered once daily and the reference formulation of immediate- release tablet of cilostazol (Cilostazol) administered twice-daily in normal healthy male and female subjects under fasting conditions.

Study Overview

• Status: Completed
• Conditions: Intermittent Claudication
• Intervention / Treatment: Drug: Cilostazol Tablet 100 mg; Drug: PMR Tablet 135 mg

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Springfield, Missouri, United States, 65802
      • Bio-Kinetic Clinical Applications, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Must be 18 to 45 years of age, inclusive, at screening.
• Absence of diseases that could affect the study outcomes.
• Having a body mass index (BMI) between 18.5 and 29.9, inclusive, at screening.
• Females must have a negative serum pregnancy test at screening.
• Understanding and willing to participate in the clinical study and able to comply with study procedures and visits.

Exclusion Criteria:

• History of bleeding tendency.
• Use of anticoagulant agent(s) within one (1) month prior to screening.
• Use of tobacco or nicotine products within six (6) months of screening.
• Intake of over the counter (OTC) or prescription drugs (other than hormonal contraceptives) within two (2) weeks prior to randomization.
• On any investigational drug(s) or therapeutic device(s) within thirty (30) days preceding screening; or anticipating use of any of these therapies during the course of the study (other than the study products).
• History of substance abuse, such as alcohol, IV drugs, and inhaled drugs, within one (1) year prior to screening.
• Known history of having Acquired Immunodeficiency Syndrome (AIDS) or positive pre-study result of infection with Human Immunodeficiency Virus (HIV); known history or positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within three (3) months of screening.
• Positive test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) at any time during the study, either asymptomatic or present with symptoms of Coronavirus disease 2019 (COVID-19).
• Pregnant or breast feeding.

• Women of child-bearing potential not using an effective birth control method. Women of child-bearing potential are defined as women physiologically capable of becoming pregnant, UNLESS they meet the following criteria:

  1. Post-menopausal: 12 months of natural (spontaneous) amenorrhea or less than twelve (12) months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40IU/L, OR;
  2. Six (6) weeks post-surgical bilateral oophorectomy with or without hysterectomy, OR;
  3. Are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g. bilateral tubal ligation, hysterectomy), hormonal contraception (e.g. implantable, injectable, vaginal, patch, and oral), and double-barrier methods. Reliable contraception should be maintained throughout the study and for seven (7) days after study discontinuation.
• Known or suspected hypersensitivity to any ingredient of the study drug(s).
• Donated blood or lost more than 150 mL of blood within three (3) months prior to randomization or plans to donate blood or plasma within four (4) weeks after completion of the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment RTRT (R: Cilostazol, T: PMR); Treatment R: One Cilostazol Tablet 100 mg at 08:00 and another at 20:00 Treatment T: Two PMR Tablet 135 mg at 08:00 Four-period dosing following the sequence of Treatment RTRT	Drug: Cilostazol Tablet 100 mg; Two oral doses (total daily dose of 200 mg); Other Names: Treatment R; Drug: PMR Tablet 135 mg; Single oral dose (total daily dose of 270 mg); Other Names: Treatment T
Other: Treatment TRTR (T: PMR, R: Cilostazol); Treatment R: One Cilostazol Tablet 100 mg at 08:00 and another at 20:00 Treatment T: Two PMR Tablet 135 mg at 08:00 Four-period dosing following the sequence of Treatment TRTR	Drug: Cilostazol Tablet 100 mg; Two oral doses (total daily dose of 200 mg); Other Names: Treatment R; Drug: PMR Tablet 135 mg; Single oral dose (total daily dose of 270 mg); Other Names: Treatment T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the curve, from time zero to last measureable time point (AUC 0-t )	0-72 hours after morning dose
AUC from time zero to infinity (AUC 0-∞)	0-72 hours after morning dose

Collaborators and Investigators

• Sponsor: Genovate Biotechnology Co., Ltd.,

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): September 20, 2022

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Peripheral Artery Disease; Cilostazol; PMR; Extended-Release Tablet of Cilostazol
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intermittent Claudication; 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: GBL22-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No