Pharmacodynamics of CGT 2168 Compared With Plavix®

Study Overview
=================
Brief Summary
-----------------
CG106 is a Phase I open-label, randomized, multiple-dose, two-way crossover study to characterize the pharmacodynamics and pharmacokinetics of the investigational fixed-dose combination product CGT 2168 (clopidogrel, 75 mg and omeprazole, 20 mg) relative to Plavix® (clopidogrel, 75 mg). Healthy volunteer subjects will undergo two dosing periods. In each 7-day dosing period, subjects will receive oral doses of study drug consisting of open-label CGT 2168 or Plavix® in the order determined by the randomization schedule. Each period of dose administration will be separated by a two-week washout period. Study exit will occur 1 week after Dosing Period 2. The expected total duration of participation is 8 weeks (56 days), including a screening visit on or within 21 days prior to enrollment. On the day before Day 1 and Day 7 in each dosing period, subjects will be admitted to the Phase I unit. Blood samples to determine ADP-induced platelet aggregation will be collected pre-dose on Day 1 and 2 h after dosing on Day 7. Plasma concentrations of clopidogrel parent and clopidogrel carboxylic acid metabolite will also be measured pre-dose on Day 1 and pre-dose and serially after dosing on Day 7.

Official Title
-----------------
A Phase I, Open-Label, Randomized, Multiple-Dose, Two-Way Crossover Study of the Pharmacodynamics of CGT 2168 Compared With Plavix®

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: CGT-2168
* Drug: Plavix


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males and females. Women of childbearing potential must have a negative pregnancy test prior to enrollment and agree to use two methods of effective barrier contraception, or a hormonal contraceptive to prevent pregnancy throughout the study. Able to comply with study procedures, which includes returning to the Phase I unit for all scheduled visits and procedures. Abstinence from tobacco use (including smoking cessation products containing nicotine) for 90 days prior to study entry, with agreement to abstain from tobacco/nicotine use throughout the study. Agreement to abstain from alcohol and caffeine ingestion from 72 h before dosing and throughout each dosing period. Able to give informed consent, and subject has signed and dated a written consent form approved by the IRB. Exclusion Criteria: Hypersensitivity to clopidogrel, omeprazole, or related drugs including inactive ingredients. BMI (body mass index) outside the range of 19-30 kg/m2. At screening, body weight less than 50 kg if male or 45 kg if female. Clinically significant abnormal findings on physical examination, clinical laboratory tests or ECG at screening. History of hypertension or 5-minute sitting screening BP ≥160/100 mmHg on measurements repeated twice. History of diabetes mellitus, renal failure, acute or chronic liver disease, including acute or chronic hepatitis, or cirrhosis. Positive HIV-1 antibody, hepatitis B surface antigen or hepatitis C antibody screening test. History of any clinically significant medical or psychiatric condition. Difficulty in swallowing medication, or any known or suspected gastrointestinal abnormality that may affect drug absorption. Participation in a previous clinical trial within 30 days prior to enrollment (check-in on Day -1 for Visit 2). Blood donation of ≥ 1 pint within 30 days or plasma donation within 14 days prior to enrollment (check-in on Day -1 for Visit 2). Use of any prescription or over-the-counter medications or ingestion of herbal drugs/dietary supplements including vitamins and minerals within 14 days prior to enrollment (check-in on Day -1 for Visit 2). Hormonal contraceptives are allowed. Subject is not willing to refrain from drinking grapefruit juice or eating grapefruit throughout study participation. Subject is an active illicit drug user or has a history of illicit drug use within the previous 12 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>CGT-2168 (clopidogrel 75 mg/omeprazole 20 mg) | Drug: CGT-2168<br>* (CGT-2168, one capsule each daily)<br>|
| Active Comparator: B<br>Plavix (clopidogrel 75 mg) | Drug: Plavix<br>* (clopidogrel, 75 mg)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of this study is inhibition of platelet aggregation (IPA) based on maximum platelet aggregation (MPA) to 5 and 20 µM ADP after 7 days daily dosing with CGT-2168 compared to Plavix®. |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual aggregation, measured 10 min after the addition of 20 and 5 µM ADP, after 7 days daily dosing with CGT 2168 compared to Plavix®. |  | 7 days | 
| Plasma PK measures of clopidogrel (parent drug and carboxylic acid metabolite) with CGT 2168 compared to Plavix®. |  | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Platelet function testing, Healthy volunteers