Cangrelor Prasugrel Transition Study

• ClinicalTrials.gov Identifier: NCT01852019
• Recruitment Status: Completed
• First Posted: May 13, 2013
• Results First Posted: May 28, 2015
• Last Update Posted: June 24, 2015
• Sponsor: The Medicines Company
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

To demonstrate that patients treated with cangrelor can be directly switched to oral prasugrel and that patients treated with prasugrel can be switched to cangrelor without a significant decrease in the extent of inhibition of platelet aggregation.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: Cangrelor; Drug: Prasugrel	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: A Study of the Transition From IV Cangrelor to Oral Prasugrel, and Prasugrel to Cangrelor, in Patients With Coronary Artery Disease.
• Study Start Date: June 2013
• Actual Primary Completion Date: July 2013
• Actual Study Completion Date: July 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Day 1 - Cangrelor + Prasugrel (60mg) post infusion; Cangrelor IV + Oral prasugrel (60mg) administered within 5 minutes after cangrelor IV discontinuation	Drug: Cangrelor; Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8; Drug: Prasugrel; Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.
Experimental: Day 8 - Prasugrel (10mg) Dosing (5 doses); Prasugrel discontinued 48h (n=6) prior to initiation of cangrelor infusion (2h)	Drug: Cangrelor; Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8; Drug: Prasugrel; Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.
Experimental: Day 1 - Cangrelor + Prasugrel (60mg) at 1.5h; Cangrelor IV + oral prasugrel (60mg) administered at 1.5h after the cangrelor infusion start time.	Drug: Cangrelor; Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8; Drug: Prasugrel; Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.
Experimental: Day 1 - Cangrelor + Prasugrel (60mg) a 1.0h; Cangrelor IV + oral prasugrel (60mg) administered at 1.0h after the cangrelor infusion start time.	Drug: Cangrelor; Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8; Drug: Prasugrel; Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.
Experimental: Day 8 - Prasugrel (10mg) Dosing (6 doses); Prasugrel discontinued 24h prior to initiation of cangrelor infusion (2h)	Drug: Cangrelor; Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8; Drug: Prasugrel; Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.

Outcome Measures

Primary Outcome Measures :

1. Extent of Preservation of Inhibitory Effect After Transition From Cangrelor to Prasugrel Compared With Effect Observed With Prasugrel Alone (Reference Timepoint) [ Time Frame: Day 1 measures taken at timepoints after cangrelor infusion end to end of Day 1 measures. ]
   A reference point for the effect of prasugrel alone was chosen for comparison and designated the final draw on study Day 1 (3.5 or 4.0 hours after cangrelor had been discontinued) as the reference for the effect of prasugrel. The extent of aggregation in the presence or absence of the study drugs was examined for each of the endpoints using light transmittance aggregometry (LTA) and expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).
2. Extent of Preservation of Inhibitory Effect of Cangrelor Treatment After Prasugrel, Compared to Treatment With Cangrelor Alone [ Time Frame: Day 8 - at 1.0 and 2.0 hours after initiation of cangrelor infusion ]
   A reference point for the inhibitory effect of cangrelor alone was chosen for comparison and designated the first draw during the cangrelor infusion (1.0 or 1.5 hours) or within 5 minutes post cangrelor infusion on Day 1. The extent of aggregation was observed during the cangrelor infusion on Day 8, either 24 or 48 hours after discontinuation of prasugrel using light transmittance aggregometry (LTA) and expressed as % aggregation in response to 20 μM adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).

Secondary Outcome Measures :

1. Extent of Preservation of Inhibitory Effect After Transition From Cangrelor to Prasugrel Compared With Effect Observed With Prasugrel Alone (Reference Timepoint) [ Time Frame: Day 1 measures taken at timepoints after cangrelor infusion end to end of Day 1 measures. ]
   A reference point for the effect of prasugrel alone was chosen for comparison and designated the final draw on study Day 1 (3.5 or 4.0 hours after cangrelor had been discontinued) as the reference for the effect of prasugrel. The extent of aggregation in the presence of absence of the study drugs was examined for each of the endpoints as assessed by platelet reaction units (PRU) from the VerifyNow P2Y12 assay.
2. Extent of Preservation of Inhibitory Effect of Cangrelor Treatment After Prasugrel, Compared to Treatment With Cangrelor Alone [ Time Frame: Day 8 - at 1.0 and 2.0 hours after initiation of cangrelor infusion ]
   A reference point for the inhibitory effect of cangrelor alone was chosen for comparison and designated the first draw during the cangrelor infusion (1.0 or 1.5 hours) or within 5 minutes post cangrelor infusion on Day 1. The extent of aggregation was observed during the cangrelor infusion on Day 8, either 24 or 48 hours after discontinuation of prasugrel as assessed by platelet reaction units (PRU) from the VerifyNow P2Y12 assay.
3. Bleeding Events in Accordance With the GUSTO Scale [ Time Frame: Day 1 through Day 8 ]
   Bleeding was assessed by history, physical exam, and complete blood count (CBC) that was performed on study Days 1 and 8. Reports of bleeding were to be evaluated by performance of a CBC. Bleeding was to be reported as recommended and quantified in accordance with the GUSTO criteria [The GUSTO Investigators, 1993].

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. greater than / equal to 18 and less than 75 years of age

2. stable coronary artery disease defined by the following criteria

   1. Previous myocardial infarction defined by admission to the hospital with elevation of markers of injury or the presence of pathologic Q waves on at least 2 contiguous electrocardiogram (ECG) leads.

      OR

   2. Previous revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).

      AND

   3. Treatment with aspirin (ASA) 81 mg daily.

Contacts and Locations

Locations

United States, Vermont

Fletcher Allen Health Care

Burlington, Vermont, United States, 05401

Sponsors and Collaborators

The Medicines Company

Investigators

• Principal Investigator: David J. Schneider; University of Vermont Medical Center

More Information

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT01852019
• Other Study ID Numbers: MDCO-CAN-13-01
• First Posted: May 13, 2013
• Results First Posted: May 28, 2015
• Last Update Posted: June 24, 2015
• Last Verified: May 2015

Keywords provided by The Medicines Company:

CAD

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Prasugrel Hydrochloride; Cangrelor; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs