Trial Outcomes & Findings for Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine (NCT NCT02403830)
NCT ID: NCT02403830
Last Updated: 2017-05-30
Results Overview
Platelet reactivity measured by VerifyNow P2Y12 2 hours after ticagrelor loading dose and reported as P2Y12 reaction units (PRU)
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
30 participants
Primary outcome timeframe
2 hours
Results posted on
2017-05-30
Participant Flow
Between August 2015 and April 2016 a total of 34 patients were recruited and consented at the University of Florida Health Science Center at UF Health Jacksonville - Division of Cardiology.
Four subjects withdrew their consent before randomization and did not receive study drug. Therefore a total of 30 patients were randomized.
Participant milestones
| Measure |
Methylnaltrexone First
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. In this arm patients received methylnaltrexone at visit 1. After a 7 ± 2 days wash-out period, patients crossed-over to the alternate study-treatment arm (placebo).
Methylnaltrexone: Methylnaltrexone will be administered diluted with 5 ml of normal saline as a single iv bolus
Morphine: After methylnaltrexone, patients will receive 5-mg intravenous morphine
Ticagrelor: After morphine administration, patients will receive a 180-mg ticagrelor loading dose
|
Placebo First
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. In this arm patients received placebo at visit 1. After a 7 ± 2 days wash-out period, patients crossed-over to the alternate study-treatment arm (methylnaltrexone).
Placebo: Placebo will be administered as a 0.9% sodium chloride iv injection
Morphine: After methylnaltrexone, patients will receive 5-mg intravenous morphine
Ticagrelor: After morphine administration, patients will receive a 180-mg ticagrelor loading dose
|
|---|---|---|
|
Visit 1
STARTED
|
15
|
15
|
|
Visit 1
COMPLETED
|
15
|
15
|
|
Visit 1
NOT COMPLETED
|
0
|
0
|
|
Visit 2
STARTED
|
14
|
15
|
|
Visit 2
COMPLETED
|
14
|
15
|
|
Visit 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine
Baseline characteristics by cohort
| Measure |
Whole Study Population
n=30 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7 ± 2 days wash-out period, patients crossed-over to the alternate study-treatment arm.
|
|---|---|
|
Age, Continuous
|
62 years
STANDARD_DEVIATION 9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 hoursPlatelet reactivity measured by VerifyNow P2Y12 2 hours after ticagrelor loading dose and reported as P2Y12 reaction units (PRU)
Outcome measures
| Measure |
Methylnaltrexone
n=30 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
Placebo
n=29 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
|---|---|---|
|
Platelet Reactivity Measured by VerifyNow P2Y12
|
130 PRU
Interval 84.0 to 176.0
|
97 PRU
Interval 59.0 to 136.0
|
SECONDARY outcome
Timeframe: 2 hoursPlatelet reactivity measured by VASP 2 hours after ticagrelor loading dose and reported as platelet reactivity index (PRI)
Outcome measures
| Measure |
Methylnaltrexone
n=30 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
Placebo
n=29 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
|---|---|---|
|
Platelet Reactivity Measured by VASP
|
47 PRI
Interval 33.0 to 60.0
|
40 PRI
Interval 29.0 to 51.0
|
SECONDARY outcome
Timeframe: 6 hoursThe area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC) was calculated based on ticagrelor plasma levels
Outcome measures
| Measure |
Methylnaltrexone
n=30 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
Placebo
n=29 Participants
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
|---|---|---|
|
AUC of Ticagrelor Plasma Levels
|
2952 ng*hr/mL
Interval 250.0 to 10133.0
|
2276 ng*hr/mL
Interval 24.0 to 7986.0
|
Adverse Events
Methylnaltrexone
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Methylnaltrexone
n=30 participants at risk
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
Placebo
n=29 participants at risk
Patients were randomly assigned in a 1:1 fashion to receive either i.v methylnaltrexone or placebo (0.9% sodium chloride iv injection). Methylnaltrexone, at a dose of 0.3 mg/Kg, was administered diluted with 5 ml of normal saline as a single i.v. bolus over 1 minute followed by morphine (5-mg intravenous bolus). Then patients received iv morphine and a loading dose of ticagrelor. After a 7±2 days wash-out patients received the alternate treatment.
Treatment effects were evaluated comparing the functional parameters observed in the overall patient population after methylnaltrexone therapy with those achieved after placebo therapy regardless of the sequence in which patients received treatment.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
16.7%
5/30 • Number of events 5 • 10 days
|
20.7%
6/29 • Number of events 6 • 10 days
|
|
Gastrointestinal disorders
nausea/vomiting
|
6.7%
2/30 • Number of events 2 • 10 days
|
6.9%
2/29 • Number of events 2 • 10 days
|
|
Cardiac disorders
hypotension
|
3.3%
1/30 • Number of events 1 • 10 days
|
0.00%
0/29 • 10 days
|
|
Cardiac disorders
dizziness
|
0.00%
0/30 • 10 days
|
3.4%
1/29 • Number of events 1 • 10 days
|
|
Cardiac disorders
hypertensive urgency
|
0.00%
0/30 • 10 days
|
3.4%
1/29 • Number of events 1 • 10 days
|
Additional Information
Dominick J. Angiolillo, MD, PhD
University of Florida College of Medicine-Jacksonville
Phone: +1-904-244-3933
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place