Pharmacodynamics of CGT 2168 Compared With Plavix®

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: CGT-2168; Drug: Plavix

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Quintiles Phase I Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

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
Experimental: A; CGT-2168 (clopidogrel 75 mg/omeprazole 20 mg)	Drug: CGT-2168; (CGT-2168, one capsule each daily)
Active Comparator: B; Plavix (clopidogrel 75 mg)	Drug: Plavix; (clopidogrel, 75 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Cogentus Pharmaceuticals
• Investigators: Study Director: Pablo Lapuerta, MD, Cogentus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: February 12, 2008
• First Submitted That Met QC Criteria: February 21, 2008
• First Posted (Estimate): February 22, 2008

Study Record Updates

• Last Update Posted (Estimate): August 26, 2008
• Last Update Submitted That Met QC Criteria: August 22, 2008
• Last Verified: August 1, 2008

More Information

Terms related to this study

• Keywords: Healthy volunteers; Platelet function testing
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: CG106