A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin

NCT00528411 | Completed Phase 2 Results

• 1 other identifier: D5130C00048
• Study Type: interventional
• Target: 123
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated how long it takes for Ticagrelor to begin working and how long it takes for it to stop working after the last dose of drug. Ticagrelor will be compared to clopidogrel, an established anti-platelet treatment for preventing blood clots, and placebo plus Aspirin.

Conditions

Coronary Artery Disease

Keywords

Coronary artery disease; CAD; heart attack; stable angina; Stable coronary artery disease

Outcome Measures

Primary Outcomes (2)

• Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose

  IPA(%)=(PAb-PAt)/PAb\*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

  At 2 hours after first dose of study drug

• Slope of Extent IPA Offset Curve 4 to 72 Hours After Last Dose of Study Drug

  IPA(%)=(PAb-PAt)/PAb\*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. The unit for the slope of IPA curve is percent/hour.

  4 to 72 Hours after last dose of study drug

Secondary Outcomes (43)

• Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose

  0.5 hours after first dose

• Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose

  1 hour after first dose

• Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose

  4 hours after first dose

• Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose

  8 hours after first dose

• Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose

  24 hours after first dose

Study Arms (3)

1

ACTIVE COMPARATOR

Aspirin + Placebo

Drug: Aspirin Tablets

2

ACTIVE COMPARATOR

Aspirin + clopidogrel

Drug: Clopidogrel (over encapsulated) capsule; Drug: Aspirin Tablets

3

EXPERIMENTAL

Aspirin + Ticagrelor

Drug: Ticagrelor Tablets; Drug: Aspirin Tablets

Interventions

Ticagrelor Tablets DRUG

Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)

3

Clopidogrel (over encapsulated) capsule DRUG

Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)

Also known as: Plavix, Clopidogrel Bisulfate

2

Aspirin Tablets DRUG

Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study.

Also known as: ASA

1; 2; 3

Eligibility Criteria

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

You may qualify if:

• Documented stable Coronary Artery Disease (stable angina, previous MI history, previous history of revascularization);
• Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception

You may not qualify if:

• History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or Coronary Artery Bypass Graft (CABG))
• History of liver or kidney disease
• Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma
• History of intolerance or allergy to Aspirin or clopidogrel

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (9)

Research Site

Baton Rouge, Louisiana, United States

Location

Research Site

Baltimore, Maryland, United States

Location

Research Site

Towson, Maryland, United States

Location

Research Site

Cincinnati, Ohio, United States

Location

Research Site

Oklahoma City, Oklahoma, United States

Location

Research Site

Philadelphia, Pennsylvania, United States

Location

Research Site

Rapid City, South Dakota, United States

Location

Research Site

Houston, Texas, United States

Location

Research Site

Sheffield, United Kingdom

Location

Related Publications (5)

• Jeong YH, Bliden KP, Antonino MJ, Park KS, Tantry US, Gurbel PA. Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies. Am Heart J. 2012 Jul;164(1):35-42. doi: 10.1016/j.ahj.2012.03.022. Epub 2012 Jun 13.

  PMID: 22795280 DERIVED

• Jeong YH, Bliden KP, Tantry US, Gurbel PA. High on-treatment platelet reactivity assessed by various platelet function tests: is the consensus-defined cut-off of VASP-P platelet reactivity index too low? J Thromb Haemost. 2012 Mar;10(3):487-9. doi: 10.1111/j.1538-7836.2011.04604.x. No abstract available.

  PMID: 22212857 DERIVED

• Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec;3(6):556-66. doi: 10.1161/CIRCGENETICS.110.958561. Epub 2010 Nov 15.

  PMID: 21079055 DERIVED

• Storey RF, Bliden KP, Patil SB, Karunakaran A, Ecob R, Butler K, Teng R, Wei C, Tantry US, Gurbel PA; ONSET/OFFSET Investigators. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol. 2010 Jul 13;56(3):185-93. doi: 10.1016/j.jacc.2010.01.062.

  PMID: 20620737 DERIVED

• Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.

  PMID: 19923168 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Infarction; Angina, Stable

Interventions

Ticagrelor; Clopidogrel; Capsules; Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Dosage Forms; Pharmaceutical Preparations; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Study Officials

• Philip Sager, MD

  AstraZeneca

  STUDY DIRECTOR

• Paul Gurbel, MD

  Platelet & Thrombosis Research, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2007
• First Posted: September 12, 2007
• Study Start: October 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: January 13, 2012
• Results First Posted: January 11, 2012

Record last verified: 2012-01

Locations

GB (1); US (8)