Trial Outcomes & Findings for Cangrelor Ticagrelor Transition Study (NCT NCT01766466)

NCT ID: NCT01766466

Last Updated: 2014-05-19

Results Overview

A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity (PR) was measured in response to 20 µmol adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: Day 1 measures taken at 2 timepoints after cangrelor infusion start: 0.5 or 1.5 hrs (Timepoint 1) and 5.25 hrs (TImepoint 2)
• Results posted on: 2014-05-19

Participant Flow

The purpose of this study was to study the pharmacodynamic characteristics of transition from IV cangrelor to oral ticagrelor, and ticagrelor to cangrelor in patients with coronary artery disease. This was a single-center study, conducted in Jan-Feb 2013.

Patients with coronary artery disease who were taking aspirin, but not P2Y12 inhibition were enrolled.

Participant milestones

Measure	Day 1 - Cangrelor + Ticagrelor (180mg) at 0.5h Cangrelor IV (2h) + oral ticagrelor (180mg) administered at 0.5h after the initiation of the cangrelor infusion.	Day 5 - Ticagrelor (90 mg) Dosing (6 Doses) Ticagrelor (90mg) discontinued 24h prior to the initiation of a 2h cangrelor infusion.	Day 1 - Cangrelor + Ticagrelor (180mg) at 1.5h Cangrelor IV (2h) + oral ticagrelor (180mg) administered at 1.5h after the initiation of the cangrelor infusion.	Day 5 - Ticagrelor (90mg) Dosing (7 Doses) Ticagrelor (90mg) discontinued 12h prior to the initiation of a 2h cangrelor infusion.
Day 1 STARTED	6	0	6	0
Day 1 COMPLETED	6	0	6	0
Day 1 NOT COMPLETED	0	0	0	0
Day 5 STARTED	0	6	0	6
Day 5 COMPLETED	0	6	0	6
Day 5 NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cangrelor Ticagrelor Transition Study

Baseline characteristics by cohort

Measure	ITT Population - Ticagrelor 6 Doses n=6 Participants On Day 1: Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. Ticagrelor (180 mg) was administered at 0.5 h or 1.5 h after the initiation of cangrelor infusion. Patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 6 doses. On Day 5: Cangrelor was administered after ticagrelor (90 mg)was discontinued 24 hours prior.	ITT Population - Ticagrelor 7 Doses n=6 Participants On Day 1: Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. Ticagrelor (180 mg) was administered at 0.5 h or 1.5 h after the initiation of cangrelor infusion. Patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 7 doses. On Day 5: Cangrelor was administered after ticagrelor (90 mg)was discontinued 12 hours prior.	Total n=12 Participants Total of all reporting groups
Age, Continuous	66.3 years STANDARD_DEVIATION 7.17 • n=5 Participants	66.5 years STANDARD_DEVIATION 4.32 • n=7 Participants	66.4 years STANDARD_DEVIATION 5.65 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 measures taken at 2 timepoints after cangrelor infusion start: 0.5 or 1.5 hrs (Timepoint 1) and 5.25 hrs (TImepoint 2)

A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity (PR) was measured in response to 20 µmol adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).

Outcome measures

Measure	All Patients n=12 Participants	Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion n=6 Participants Cangrelor was administered as IV infusion for 2 hours.	Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion n=6 Participants Cangrelor was administered as IV infusion for 2 hours.
Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) Reference 0.5/1.25 hours - PR	1.7 percentage of platelet reactivity (PR) Standard Deviation 1.7	1.3 percentage of platelet reactivity (PR) Standard Deviation 2.0	2 percentage of platelet reactivity (PR) Standard Deviation 1.5
Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) 1.75 hours - PR	2.2 percentage of platelet reactivity (PR) Standard Deviation 1.4	2 percentage of platelet reactivity (PR) Standard Deviation 1.8	2.3 percentage of platelet reactivity (PR) Standard Deviation 1.0
Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) 2.0 hours - PR	2.3 percentage of platelet reactivity (PR) Standard Deviation 2.2	1.2 percentage of platelet reactivity (PR) Standard Deviation 1.9	3.5 percentage of platelet reactivity (PR) Standard Deviation 1.9

PRIMARY outcome

Timeframe: Day 5 at 1.0 and 2.0 hours after the initiation of cangrelor infusion

A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor.

Residual platelet reactivity (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). Residual platelet reactivity (PR) was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response).

Outcome measures

Measure	All Patients n=12 Participants	Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion n=6 Participants Cangrelor was administered as IV infusion for 2 hours.	Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion n=6 Participants Cangrelor was administered as IV infusion for 2 hours.
Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor 1.0 hours - PR	1.5 percentage of platelet reactivity (PR) Standard Deviation 1.5	1.5 percentage of platelet reactivity (PR) Standard Deviation 1.6	1.5 percentage of platelet reactivity (PR) Standard Deviation 1.5
Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor 2.0 hours - PR	1.3 percentage of platelet reactivity (PR) Standard Deviation 1.6	1.2 percentage of platelet reactivity (PR) Standard Deviation 1.5	1.5 percentage of platelet reactivity (PR) Standard Deviation 1.9

PRIMARY outcome

Timeframe: Day 1 at 2.25, 2.5, 2.75, 3 and 4 hrs following initiation of cangrelor infusion

Blood samples were taken for platelet function studies to conduct pharmacodynamic assessments including LTA.

A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor.

Residual platelet reactivity (PR) (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response).

Outcome measures

Measure	All Patients n=12 Participants	Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion n=6 Participants Cangrelor was administered as IV infusion for 2 hours.	Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion n=6 Participants Cangrelor was administered as IV infusion for 2 hours.
Extent of Aggregation Response During Ticagrelor Treatment Reference 5.25 hours - PR	4 percentage of platelet reactivity (PR) Standard Deviation 3.4	2.2 percentage of platelet reactivity (PR) Standard Deviation 2.7	5.8 percentage of platelet reactivity (PR) Standard Deviation 3.1
Extent of Aggregation Response During Ticagrelor Treatment 2.25 hours - PR	12 percentage of platelet reactivity (PR) Standard Deviation 11	11 percentage of platelet reactivity (PR) Standard Deviation 12	13 percentage of platelet reactivity (PR) Standard Deviation 9.3
Extent of Aggregation Response During Ticagrelor Treatment 2.5 hours - PR	19 percentage of platelet reactivity (PR) Standard Deviation 16	21 percentage of platelet reactivity (PR) Standard Deviation 17	16 percentage of platelet reactivity (PR) Standard Deviation 15
Extent of Aggregation Response During Ticagrelor Treatment 2.75 hours - PR	10 percentage of platelet reactivity (PR) Standard Deviation 9.2	7.8 percentage of platelet reactivity (PR) Standard Deviation 7.2	12 percentage of platelet reactivity (PR) Standard Deviation 11
Extent of Aggregation Response During Ticagrelor Treatment 3 hours - PR	7.1 percentage of platelet reactivity (PR) Standard Deviation 6.3	4.5 percentage of platelet reactivity (PR) Standard Deviation 3.4	10 percentage of platelet reactivity (PR) Standard Deviation 7.6
Extent of Aggregation Response During Ticagrelor Treatment 4 hours - PR	4.6 percentage of platelet reactivity (PR) Standard Deviation 3.6	2.5 percentage of platelet reactivity (PR) Standard Deviation 1.9	6.7 percentage of platelet reactivity (PR) Standard Deviation 3.7

Adverse Events

Cangrelor + Ticagrelor 90mg (6 Doses)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cangrelor + Ticagrelor 90mg (7 Doses)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cangrelor + Ticagrelor 90mg (6 Doses) n=6 participants at risk Ticagrelor was discontinued 24 h prior to cangrelor infusion	Cangrelor + Ticagrelor 90mg (7 Doses) n=6 participants at risk Ticagrelor discontinued 12 h prior to cangrelor infusion
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 1	0.00% 0/6
General disorders Edema peripheral	0.00% 0/6	16.7% 1/6 • Number of events 1

Additional Information

Jayne Prats, PhD - VP, Global Knowledge Management

The Medicines Company

Phone: 888.779.MDCO

Email: jayne.prats@themedco.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER