The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease

NCT01260584 | Completed Phase 4 Results

• 1 other identifier: CS747S-B-U4002
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 3

Brief Summary

This study is being conducted to determine if smoking will influence the platelet aggregation inhibition ability of clopidogrel and prasugrel. It will also determine if smoking has any effect on the plasma concentrations of the active metabolite of prasugrel and the active and inactive metabolites of clopidogrel. The primary hypothesis is that smoking status will influence the antiplatelet effects and active metabolite concentrations of clopidogrel but will have no impact on prasugrel's antiplatelet effects or active metabolite concentrations.

Conditions

Coronary Artery Disease

Keywords

thienopyridine; antiplatelet; prasugrel; clopidogrel

Outcome Measures

Primary Outcomes (1)

• Inhibition of Platelet Aggregation (IPA) in Prasugrel-treated and Clopidogrel-treated Smokers and Non-smokers Following 9 Days of Maintenance Therapy.

  IPA will be measured by the Accumetrics P2Y12 Assay Device. Response will be assessed in P2Y12 Reaction Units and as Platelet Reactivity Index (vasodilator-stimulated phosphoprotein assay).

  Baseline to day 10 for Active Treatment Periods 1 and 2

Secondary Outcomes (6)

• Assessment of P2Y12 Reaction Units (PRU) by Treatment and Smoking Status

  Day 10 for Active Treatment Periods 1 and 2

• Assessment of Vasodilator Stimulated Phosphoprotein (VASP) by Treatment and Smoking Status

  Day 10 for Active Treatment Periods 1 and 2

• Responder Rate by Treatment and Smoking Status Based on P2Y12 Reaction Units (PRU) <= 235

  Day 10 for Active Treatment Periods 1 and 2

• Responder Rate by Treatment and Smoking Status Based on Platelet Reactivity Index (PRI) <= 50%

  Day 10 for Active Treatment Periods 1 and 2

• Characterization of the Pharmacokinetics (PK) Area Under Curve (AUC)(0-Last) of the Active Metabolite of Prasugrel and the Active Metabolite of Clopidogrel in Smokers and Non-smokers

  After dose on Day 10 of Active Treatment Periods 1 and 2

Study Arms (2)

Prasugrel

EXPERIMENTAL

Prasugrel 10 mg film-coated tablet daily dose × 10 days. To maintain blinding, placebo film-coated tablets matching clopidogrel in appearance will be given daily × 10 days to subjects in the prasugrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Drug: Prasugrel

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel 75 mg film-coated tablet daily dose x 10 days To maintain blinding, placebo film-coated tablets matching prasugrel in appearance will be given daily × 10 days to subjects in the clopidogrel treatment group. In addition, aspirin 81 mg to 325 mg daily will be taken.

Drug: Clopidogrel

Interventions

Prasugrel DRUG

One 10 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Also known as: Effient

Prasugrel

Clopidogrel DRUG

One 75 mg film-coated, oral tablet daily x 10 days. In addition, aspirin 81 mg to 325 mg daily will be taken.

Also known as: Plavix

Clopidogrel

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects \> or = 18 years and \<75 years of age;
• Weight \> or = 60 kg;
• On aspirin therapy (81 mg to 325 mg daily) at the time of screening and able to maintain a consistent aspirin dosing regimen from the baseline visit through the final study visit;
• Subjects who do not have contraindications for a thienopyridine (ie, prasugrel, clopidogrel, or ticlopidine) and have a history of stable atherosclerosis represented by CAD, defined as any of the following:
• Chronic stable angina;
• Documented prior ACS event \> or = 30 days before screening and not currently prescribed or currently on thienopyridine therapy;
• Previous coronary revascularization including percutaneous transluminal coronary angioplasty, stent, or coronary artery bypass graft;
• Coronary Artery Disease (\> or = 40% obstruction) in at least one coronary vessel after angiography;
• Documented history of positive stress test; or
• High coronary artery calcium score (\> or = 90th percentile for age and gender) determined by cardiac computed tomography scan;
• Current smokers who smoke \> or = ½ pack per day of cigarettes with a NicAlert™ level of 6;
• Non-smokers with a NicAlert level of 0, 1, or 2;
• Female subjects who meet one of the following:
• Women of childbearing potential with a negative serum pregnancy test at screening, who are not breastfeeding, do not plan to become pregnant during the study, and agree to use an approved method of birth control during the study. Approved methods of birth control are intrauterine device, diaphragm plus spermicide, or female condom plus spermicide. Abstinence, partner's use of condoms, partner's vasectomy, and hormonal contraceptives are NOT acceptable methods of contraception;
• Women who have been postmenopausal for at least 1 year or have had a hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation at least 6 months prior to signing the Informed Consent Form (ICF); and

You may not qualify if:

• Subjects who received a bare metal stent and/or a drug-eluting stent within the last 12 months;
• Subjects who have had an angiogram \< or = 7 days before randomization;
• Any other formal indication for the use of a thienopyridine;
• Subjects with a history of refractory ventricular arrhythmias;
• Subjects with a history of an implantable defibrillator device;
• Subjects with a history or evidence of congestive heart failure (New York Heart Association Class III or above) within 6 months prior to screening;
• Subjects with significant hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) at either the time of screening or baseline assessment;
• Any known contraindication to treatment with an anticoagulant or antiplatelet agent;
• Prior history or clinical suspicion of cerebral vascular malformations, intracranial tumor, transient ischemic attack, or stroke, or recent history (within 3 months) of head trauma;
• Prior history or presence of significant bleeding disorders (eg, hematemesis, melena, severe or recurrent epistaxis, hemoptysis, hematuria, or intraocular bleeding);
• History (within the last 5 years) or presence of gastric ulcers. Previous history of duodenal ulcer is acceptable but must have been successfully surgically or medically treated with no further evidence of disease in the past 6 months (from screening);
• Prior history of abnormal bleeding tendency (ie, prolonged bleeding on dental extraction, tonsillectomy, or previous surgical procedure);
• Known prior history or presence of thrombocytopenia (platelet count \<100,000/mm3) or thrombocytosis (platelet count \>500,000/mm3) or recent history (within 6 months) of hemoglobin \<10 mg/dL;
• International normalized ratio (INR) \>1.5 or activated partial thromboplastin time (aPTT) \> upper limit of normal (ULN) of laboratory reference range at screening;
• History of major surgery, severe trauma, fracture, or organ biopsy within 3 months prior to enrollment;

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (3)

Sanai Center for Thrombosis Research

Baltimore, Maryland, 21215, United States

Location

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45212, United States

Location

The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Related Publications (1)

• Gurbel PA, Bliden KP, Logan DK, Kereiakes DJ, Lasseter KC, White A, Angiolillo DJ, Nolin TD, Maa JF, Bailey WL, Jakubowski JA, Ojeh CK, Jeong YH, Tantry US, Baker BA. The influence of smoking status on the pharmacokinetics and pharmacodynamics of clopidogrel and prasugrel: the PARADOX study. J Am Coll Cardiol. 2013 Aug 6;62(6):505-12. doi: 10.1016/j.jacc.2013.03.037. Epub 2013 Apr 16.

  PMID: 23602770 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Brian Baker
• Organization: Daiichi Sankyo

bbaker@dsi.com

973-944-2712

Study Officials

• Paul Gurbel, MD

  Sinai Center for Thrombosis Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2010
• First Posted: December 15, 2010
• Study Start: November 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: January 9, 2019
• Results First Posted: December 12, 2012

Record last verified: 2012-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (3)