Trial Outcomes & Findings for Fasted Bioavailability Study of Cilostazol Tablets, 50mg (NCT NCT00685802)

NCT ID: NCT00685802

Last Updated: 2009-12-22

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after drug administration.

Results posted on

2009-12-22

Participant Flow

Thirty-two healthy adult male and female volunteers from the community-at-large were enrolled.

Participant milestones

Participant milestones
Measure	Cilostazol 50 mg Tablets Then Pletal® 50 mg Tablets On the morning of Day 1 subjects received two tablets of the test formulation, Cilostazol 50 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 two tablets of the reference formulation, Pletal® 50 mg, after an overnight fast of at least 10 hours.	Pletal® 50 mg Tablets Then Cilostazol 50 mg Tablets On the morning of Day 1 subjects received two tablets of the reference formulation, Pletal® 50 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 two tablets of the test formulation, Cilostazol 50 mg, after an overnight fast of at least 10 hours.
First Intervention STARTED	16	16
First Intervention COMPLETED	16	16
First Intervention NOT COMPLETED	0	0
Washout Period of 7 Days STARTED	16	16
Washout Period of 7 Days COMPLETED	14	15
Washout Period of 7 Days NOT COMPLETED	2	1
Second Intervention STARTED	14	15
Second Intervention COMPLETED	14	15
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cilostazol 50 mg Tablets Then Pletal® 50 mg Tablets On the morning of Day 1 subjects received two tablets of the test formulation, Cilostazol 50 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 two tablets of the reference formulation, Pletal® 50 mg, after an overnight fast of at least 10 hours.	Pletal® 50 mg Tablets Then Cilostazol 50 mg Tablets On the morning of Day 1 subjects received two tablets of the reference formulation, Pletal® 50 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 two tablets of the test formulation, Cilostazol 50 mg, after an overnight fast of at least 10 hours.
Washout Period of 7 Days Protocol Violation	2	0
Washout Period of 7 Days Withdrawal by Subject	0	1

Baseline Characteristics

Fasted Bioavailability Study of Cilostazol Tablets, 50mg

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cilostazol 50 mg Tablets and Pletal® 50 mg Tablets n=32 Participants 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 two tablets of either Cilostazol 50 mg or Pletal® 50 mg following an overnight fast of at least 10 hours.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	32.25 years STANDARD_DEVIATION 11.98 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	26 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after drug administration.

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

Outcome measures

Outcome measures
Measure	Cilostazol 50 mg Tablets n=29 Participants On the morning of Day 1 subjects received two tablets of either the test formulation, cilostazol 50mg, or the reference formulation, Pletal® 50 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.	Pletal® 50 mg Tablets n=29 Participants On the morning of Day 1 subjects received two tablets of either the test formulation, cilostazol 50mg, or the reference formulation, Pletal® 50 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.
Maximum Plasma Concentration (Cmax)	565.52 ng/mL Standard Deviation 155.67	570.60 ng/mL Standard Deviation 174.72

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Cilostazol 50 mg Tablets n=29 Participants On the morning of Day 1 subjects received two tablets of either the test formulation, cilostazol 50mg, or the reference formulation, Pletal® 50 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.	Pletal® 50 mg Tablets n=29 Participants On the morning of Day 1 subjects received two tablets of either the test formulation, cilostazol 50mg, or the reference formulation, Pletal® 50 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.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)]	7,265.38 ng-hr/mL Standard Deviation 1,975.87	7,354.03 ng-hr/mL Standard Deviation 2,048.83

PRIMARY outcome

Population: Pharmacokinetic analyses of cilostazol and Pletal® are based on 28 and 27 subjects, respectively. Reliable estimates could not be obtained for one subject administered Cilostazol and two subjects administered Pletal® because there was not a smooth decline in concentrations in the terminal phase of elimination.

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 plasma concentration to the elimination rate constant.

Outcome measures

Outcome measures
Measure	Cilostazol 50 mg Tablets n=28 Participants On the morning of Day 1 subjects received two tablets of either the test formulation, cilostazol 50mg, or the reference formulation, Pletal® 50 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.	Pletal® 50 mg Tablets n=27 Participants On the morning of Day 1 subjects received two tablets of either the test formulation, cilostazol 50mg, or the reference formulation, Pletal® 50 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.
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]	8,641.26 ng-hr/mL Standard Deviation 3,010.04	8,706.54 ng-hr/mL Standard Deviation 3,142.36

Adverse Events

Cilostazol 50 mg Tablets

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Pletal® 50 mg Tablets

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Mutual Pharmaceutical Company, Inc.

Phone: 215-697-1743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Cilostazol 50 mg Tablets n=31 participants at risk 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 two tablets of either cilostazol 50 mg or Pletal® 50 mg following an overnight fast of at least 10 hours.	Pletal® 50 mg Tablets n=30 participants at risk 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 two tablets of either cilostazol 50 mg or Pletal® 50 mg following an overnight fast of at least 10 hours.
Nervous system disorders Headache	19.4% 6/31 • Number of events 6 • All adverse events were recorded during the 14 day course of the study.	16.7% 5/30 • Number of events 5 • All adverse events were recorded during the 14 day course of the study.
Cardiac disorders Bradycardia	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Cardiac disorders Hypertension	3.2% 1/31 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.	0.00% 0/30 • All adverse events were recorded during the 14 day course of the study.
Cardiac disorders Tachycardia	3.2% 1/31 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Gastrointestinal disorders Nausea	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Blood and lymphatic system disorders Anemia	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Blood and lymphatic system disorders Anemia hypochrom	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Cardiac disorders hypotension	3.2% 1/31 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.	0.00% 0/30 • All adverse events were recorded during the 14 day course of the study.
Blood and lymphatic system disorders Leukocytosis	3.2% 1/31 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.	0.00% 0/30 • All adverse events were recorded during the 14 day course of the study.
Metabolism and nutrition disorders Albuminuria	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Metabolism and nutrition disorders Hyperglycemia	3.2% 1/31 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Nervous system disorders paresthesia circumoral	3.2% 1/31 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.	0.00% 0/30 • All adverse events were recorded during the 14 day course of the study.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Respiratory, thoracic and mediastinal disorders Rhinitis	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.
Renal and urinary disorders Hematuria	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	6.7% 2/30 • Number of events 2 • All adverse events were recorded during the 14 day course of the study.
Renal and urinary disorders Urine abnormal	0.00% 0/31 • All adverse events were recorded during the 14 day course of the study.	3.3% 1/30 • Number of events 1 • All adverse events were recorded during the 14 day course of the study.