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

NCT01860105 | Completed Phase 1

• 1 other identifier: MDCO-157-12-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics and Pharmacodynamics in Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Dose Response of MDCO-157 (3 doses) compared to Plavix 300 mg

  To evaluate the dose-response of MDCO-157 (at 3 doses) compared to Plavix (300 mg), using Emax and AUEC with VASP, over 24 hours: * Maximum effect of P2Y12 receptor inhibition (Emax) using VASP (flow cytometry) * Area under the effect of P2Y12 receptor inhibition time curve (AUEC) using VASP (flow cytometry)

  24 hr

Secondary Outcomes (4)

• Pharmacokinetics (PK) of MDCO-157 and its metabolites

  24 hrs

• Safety and tolerability

  48 hrs post each treatment period

• Dose response of MDCO-157 as assessed by LTA

  24 hours

• Dose response of MDCO-157 as assess by VerifyNow P2Y12 assay

  24 hours

Study Arms (4)

75mg MDCO-157

ACTIVE COMPARATOR

iv

Drug: MDCO-157

150mg MDCO-157

ACTIVE COMPARATOR

iv

Drug: MDCO-157

300mg MDCO-157

ACTIVE COMPARATOR

iv

Drug: MDCO-157

300mg PLAVIX

ACTIVE COMPARATOR

oral

Drug: PLAVIX

Interventions

MDCO-157 DRUG

intravenous administration

150mg MDCO-157; 300mg MDCO-157; 75mg MDCO-157

PLAVIX DRUG

oral administration

300mg PLAVIX

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (1)

Groupe Hospitalier Pitié-Salpêtrière

Paris, France

Location

Related Publications (1)

• Collet JP, Funck-Brentano C, Prats J, Salem JE, Hulot JS, Guilloux E, Hu MY, He K, Silvain J, Gallois V, Brugier D, Anzaha G, Galier S, Nicolas N, Montalescot G. Intravenous Clopidogrel (MDCO-157) Compared with Oral Clopidogrel: The Randomized Cross-Over AMPHORE Study. Am J Cardiovasc Drugs. 2016 Feb;16(1):43-53. doi: 10.1007/s40256-015-0145-0.

  PMID: 26386578 DERIVED

MeSH Terms

Interventions

Clopidogrel

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: May 22, 2013
• Study Start: September 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: February 22, 2018

Record last verified: 2018-02

Locations

FR (1)