Trial Outcomes & Findings for Co-Administration of MK-4618 With Antihypertensive Agents (MK-4618-010) (NCT NCT01337674)
NCT ID: NCT01337674
Last Updated: 2018-12-24
Results Overview
An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product is also an adverse experience. The percentage of participants with a clinical or laboratory adverse experience was recorded.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
Up to 42 days
Results posted on
2018-12-24
Participant Flow
Participant milestones
| Measure |
Panel A: MK-4618 + Met → PBO + Met
Once daily oral dose of MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 1 followed by once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of metoprolol (Met) for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met → MK-4618 + Met
Once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 1 followed by MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of metoprolol (Met) for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo → PBO + Amlo
Once daily oral dose of MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 1 followed by once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of amlodipine (Amlo) for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo → MK-4618 + Amlo
Once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 1 followed by MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of amlodipine (Amlo) for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
6
|
7
|
6
|
7
|
|
Treatment Period 1
COMPLETED
|
6
|
6
|
6
|
6
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
1
|
0
|
1
|
|
Two-week Washout Period
STARTED
|
6
|
6
|
6
|
6
|
|
Two-week Washout Period
COMPLETED
|
6
|
6
|
6
|
6
|
|
Two-week Washout Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
6
|
6
|
6
|
6
|
|
Treatment Period 2
COMPLETED
|
6
|
6
|
5
|
6
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Panel A: MK-4618 + Met → PBO + Met
Once daily oral dose of MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 1 followed by once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of metoprolol (Met) for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met → MK-4618 + Met
Once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 1 followed by MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of metoprolol (Met) for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo → PBO + Amlo
Once daily oral dose of MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 1 followed by once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of amlodipine (Amlo) for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo → MK-4618 + Amlo
Once daily oral dose of placebo (two tablets) on Days 1 through 7 in Period 1 followed by MK-4618 (two 50-mg tablets) on Days 1 through 7 in Period 2. Participants receive previously prescribed daily dose of amlodipine (Amlo) for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Treatment Period 1
Adverse Event
|
0
|
1
|
0
|
0
|
|
Treatment Period 1
Discontinued due to blood draws
|
0
|
0
|
0
|
1
|
|
Treatment Period 2
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Co-Administration of MK-4618 With Antihypertensive Agents (MK-4618-010)
Baseline characteristics by cohort
| Measure |
Panel A Participants
n=13 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) or placebo (two tablets) on Days 1 through 7 in Period 1 followed by the crossover treatment in Period 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B Participants
n=13 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) or placebo (two tablets) on Days 1 through 7 in Period 1 followed by the crossover treatment in Period 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.8 Years
n=5 Participants
|
55.2 Years
n=7 Participants
|
54.5 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 42 daysPopulation: The All Subjects as Treated population included all participants who received \>=1 dose of study drug
An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product is also an adverse experience. The percentage of participants with a clinical or laboratory adverse experience was recorded.
Outcome measures
| Measure |
Panel A: MK-4618 + Met
n=12 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met
n=13 Participants
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo
n=12 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo
n=13 Participants
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Percentage of Participants With a Clinical or Laboratory Adverse Experience
|
33.3 Percentage of participants
|
53.8 Percentage of participants
|
41.7 Percentage of participants
|
61.5 Percentage of participants
|
PRIMARY outcome
Timeframe: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7Population: The All Subjects as Treated population included all participants who received \>=1 dose of study drug.
Semi-recumbent and standing systolic blood pressure was measured predose and at intervals up to 24 hours postdose on Day 1 and Day 7. The baseline value is the average of measurements taken in the hour before dosing. Participants were to rest quietly in a semi-recumbent position for at least 10 minutes before each semi-recumbent measurement.
Outcome measures
| Measure |
Panel A: MK-4618 + Met
n=12 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met
n=13 Participants
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
Semi-recumbent, Day 1
|
16.03 mmHg
Interval 9.46 to 22.61
|
17.25 mmHg
Interval 10.93 to 23.57
|
—
|
—
|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
Semi-recumbent, Day 7
|
14.38 mmHg
Interval 7.81 to 20.96
|
12.10 mmHg
Interval 5.78 to 18.42
|
—
|
—
|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
Standing, Day 1
|
14.79 mmHg
Interval 7.43 to 22.15
|
13.14 mmHg
Interval 6.01 to 20.26
|
—
|
—
|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
Standing, Day 7
|
6.12 mmHg
Interval -1.24 to 13.49
|
7.21 mmHg
Interval 0.09 to 14.34
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7Population: The All Subjects as Treated population included all participants who received \>=1 dose of study drug.
Semi-recumbent and standing systolic blood pressure was measured predose and at intervals up to 24 hours postdose on Day 1 and Day 7. The baseline value is the average of measurements taken in the hour before dosing. Participants were to rest quietly in a semi-recumbent position for at least 10 minutes before each semi-recumbent measurement.
Outcome measures
| Measure |
Panel A: MK-4618 + Met
n=12 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met
n=13 Participants
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
Semi-recumbent, Day 1
|
14.69 mmHg
Interval 9.65 to 19.72
|
12.74 mmHg
Interval 7.87 to 17.61
|
—
|
—
|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
Semi-recumbent, Day 7
|
10.52 mmHg
Interval 5.48 to 15.55
|
16.43 mmHg
Interval 11.56 to 21.3
|
—
|
—
|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
Standing, Day 1
|
6.50 mmHg
Interval 1.27 to 11.73
|
12.75 mmHg
Interval 7.7 to 17.79
|
—
|
—
|
|
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
Standing, Day 7
|
6.33 mmHg
Interval 1.1 to 11.57
|
7.90 mmHg
Interval 2.85 to 12.95
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose and up to 24 hours postdose on Day 7Population: The Per Protocol population included participants who complied with the protocol sufficiently to ensure that the data will likely exhibit the effects of treatment, according to the underlying scientific model.
Blood samples were collected on Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose for the determination of plasma MK-4618 concentration. The hypothesis for this outcome is that the steady-state AUC0-24hr for MK-4618 is \>=0.47 uM\*hr.
Outcome measures
| Measure |
Panel A: MK-4618 + Met
n=12 Participants
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met
n=12 Participants
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618
|
2.60 uM*hr
Interval 2.09 to 3.24
|
4.60 uM*hr
Interval 3.69 to 5.74
|
—
|
—
|
Adverse Events
Panel A: MK-4618 + Met
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Panel A: PBO + Met
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Panel B: MK-4618 + Amlo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Panel B: PBO + Amlo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Panel A: MK-4618 + Met
n=12 participants at risk
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel A: PBO + Met
n=13 participants at risk
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of metoprolol for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: MK-4618 + Amlo
n=12 participants at risk
Once daily oral dose of MK-4618 (two 50-mg tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
Panel B: PBO + Amlo
n=13 participants at risk
Once daily oral dose of placebo (two tablets) in Period 1 or 2. Participants receive previously prescribed daily dose of amlodipine for the duration of the study. A 2-week washout period follows Period 1.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
General disorders
Application site pain
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
General disorders
Application site rash
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
General disorders
Asthenia
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
General disorders
Chest pain
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
General disorders
Vessel puncture site swelling
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Investigations
Weight increased
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Number of events 2 • Up to 42 days
|
38.5%
5/13 • Number of events 6 • Up to 42 days
|
16.7%
2/12 • Number of events 4 • Up to 42 days
|
15.4%
2/13 • Number of events 2 • Up to 42 days
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Reproductive system and breast disorders
Penile pain
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/12 • Up to 42 days
|
7.7%
1/13 • Number of events 1 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Vascular disorders
Flushing
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
|
Vascular disorders
Hot flush
|
8.3%
1/12 • Number of events 1 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
0.00%
0/12 • Up to 42 days
|
0.00%
0/13 • Up to 42 days
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme, Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission
- Publication restrictions are in place
Restriction type: OTHER