Appraisal of MDCO-157 and Plavix® Pharmacokinetics and Pharmacodynamics in Healthy Volunteers With an Evaluation (AMPHORE)

The Medicines Company

Status and phase: Completed; Phase 1

Conditions: Pharmacokinetics and Pharmacodynamics in Healthy Volunteers

Treatments: Drug: MDCO-157; Drug: PLAVIX

Study type: Interventional

Funder types: Industry

Identifiers

NCT01860105

MDCO-157-12-01

Details and patient eligibility

About

Following a first, dose ascending study that enrolled 144 normal healthy volunteers (NHVs), this study, to be conducted in approximately 36 NHVs, will provide pertinent information in determining the dose-response of MDCO-157 for platelet aggregation inhibition and P2Y12 receptor inhibition effects and in selection of doses that match the antiplatelet effects of 300 mg PLAVIX® ®. The study will also provide additional data for pharmacokinetics (PK), safety and tolerability of single doses of MDCO-157.

Enrollment: 37 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Healthy males or females 18 to 45 years of age, inclusive.
• Provide written informed consent for genetic testing and written informed consent for the study before initiation of any study related procedures
• Affiliated to the French social security system
• Screening and baseline Fridericia's correction (QTcF) interval < 450 msec and baseline heart rate between 50 and 100 bpm (inclusive)

Exclusion Criteria:

• Known or suspected hypersensitivity or allergy to clopidogrel, Captisol, PLAVIX® , or its excipients
• Body mass index <20 or > 30 kg/m²
• Inability to communicate with the investigator or comply with study related procedures, or high likelihood of being lost to follow up
• Known or suspected pregnancy or lactating female
• Medical history, physical examination including 12-lead ECG or laboratory evaluation conducted at the screening visit with results indicative of any disease or condition which might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk
• Tobacco product use within the last 6 months prior to dosing
• Platelet count < 150,000/µL
• A personal or family history of coagulation or bleeding disorders or reasonable suspicion of vascular malformations
• Active pathological bleeding such as peptic ulcer or intracranial hemorrhage
• Positive screen for Hepatitis B (Hepatitis B Surface Antigen HBsAg), Hepatitis C (Hepatitis C Antibody), or HIV (anti-HIV 1/2)
• Received an investigational drug within a period of 30 days or 5 half-lives, whichever is longer, prior to enrollment in the study
• Use of aspirin, other non-steroidal anti-inflammatory drugs, CYP3A4 inhibitors (ketoconazole), CYP2C19 inhibitors (eg, omeprazole) or other drugs known to affect platelet function or coagulation within 14 days prior to receiving study drug (MDCO-157 or oral clopidogrel)
• Grapefruit within 10 days prior to receiving study drug (MDCO-157 or PLAVIX®)
• Use of any over-the-counter medication, including herbal products, within 7 days prior to administration of study drug (MDCO-157 or PLAVIX®), except for up to 2 grams of acetaminophen per day for up to 3 days for pain control

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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37 participants in 4 patient groups

75mg MDCO-157

Active Comparator group

Description:

iv

Treatment:

Drug: MDCO-157

150mg MDCO-157

Active Comparator group

Description:

iv

Treatment:

Drug: MDCO-157

300mg MDCO-157

Active Comparator group

Description:

iv

Treatment:

Drug: MDCO-157

300mg PLAVIX

Active Comparator group

Description:

oral

Treatment:

Drug: PLAVIX