CompletedNCT01337674Updated Dec 24, 2018Results posted

Co-Administration of MK-4618 With Antihypertensive Agents (MK-4618-010)

A Phase 1 interventional study of MK-4618 and Placebo for MK-4618 in Hypertension, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-12-24.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 26
Allocation: Randomized
Ages: 18 Years to 80 Years
Sex: All

Study summary

This study will evaluate the safety and tolerability of MK-4618 when coadministered with antihypertensive agents and will evaluate changes in blood pressure following co-administration of MK-4618 with a beta blocker and a vasodilator. The primary hypothesis of the study is that MK-4618 does not result in a clinically meaningful change in systolic blood pressure relative to placebo when co-administered with a beta-blocker or with amlodipine.

Conditions studied

Hypertension

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In context

Hypertension

6,689 studies on the registry are indexed under Hypertension; 964 are open to participants now.

This study's enrollment of 26 is below the median of 90 across 4,994 interventional studies indexed under Hypertension.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male or female not of childbearing potential
Not a nursing mother
Must be on stable dose of a beta blocker (Panel A only) or amlodipine (Panel B only) for the treatment of hypertension for at least 6 weeks prior to enrollment. Must take the designated daily dose of metoprolol or amlodipine for the duration of the study
In good health other than hypertension
Nonsmoker
Participant has a resting systolic blood pressure \<150 and >95 mmHg and a diastolic blood pressure \<95 and >75 mmHg at prestudy clinical evaluation

Exclusion criteria

Exclusion Criteria:

Any illness that might confound the results of the study or pose a risk by participation
History of orthostatic hypotension (decrease in blood pressure upon standing accompanied by symptoms of lightheadedness or dizziness)
History of cancer, excepting certain skin or cervical cancers or cancers that were treated successfully 10 or more years prior to screening
Condition for which there is a warning, contraindication, or precaution against the use of extended release metoprolol (Panel A) or amlodipine (Panel B)
Consumes excessive amounts of alcohol or caffeine daily
Has multiple and/or severe allergies (including latex allergy) or has had an anaphylactic reaction or significant intolerance to drugs or food
Uses illicit drugs or has a history of drug abuse

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 26 participants (actual)

Study arms

Experimental
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.
Drug: MK-4618 · Drug: Placebo for MK-4618 · Drug: Metoprolol
Experimental
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.
Drug: MK-4618 · Drug: Placebo for MK-4618 · Drug: Metoprolol
Experimental
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.
Drug: MK-4618 · Drug: Placebo for MK-4618 · Drug: Amlodipine
Experimental
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.
Drug: MK-4618 · Drug: Placebo for MK-4618 · Drug: Amlodipine

Interventions

DrugMK-4618
Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7
DrugPlacebo for MK-4618
Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7
DrugMetoprolol
Previously prescribed daily dose of open-label metoprolol for the duration of the study
Also known as: Toprol-XL
DrugAmlodipine
Previously prescribed daily dose of open-label amlodipine for the duration of the study
Also known as: Norvasc

What researchers measure

Primary outcomes

Percentage of Participants With a Clinical or Laboratory Adverse Experience
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.
Time frame: Up to 42 days
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
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.
Time frame: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7
Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
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.
Time frame: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7

Secondary outcomes

Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618
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.
Time frame: Predose and up to 24 hours postdose on Day 7

Results

Posted Feb 2, 2016

Participant flow

Treatment Period 1

Participant flow — Treatment Period 1
Milestone	Panel A: MK-4618 + Met → PBO + Met	Panel A: PBO + Met → MK-4618 + Met	Panel B: MK-4618 + Amlo → PBO + Amlo	Panel B: PBO + Amlo → MK-4618 + Amlo
Started	6	7	6	7
Completed	6	6	6	6
Not completed	0	1	0	1
Withdrew: Adverse event	0	1	0	0
Withdrew: Discontinued due to blood draws	0	0	0	1

Two-week Washout Period

Participant flow — Two-week Washout Period
Milestone	Panel A: MK-4618 + Met → PBO + Met	Panel A: PBO + Met → MK-4618 + Met	Panel B: MK-4618 + Amlo → PBO + Amlo	Panel B: PBO + Amlo → MK-4618 + Amlo
Started	6	6	6	6
Completed	6	6	6	6
Not completed	0	0	0	0

Treatment Period 2

Participant flow — Treatment Period 2
Milestone	Panel A: MK-4618 + Met → PBO + Met	Panel A: PBO + Met → MK-4618 + Met	Panel B: MK-4618 + Amlo → PBO + Amlo	Panel B: PBO + Amlo → MK-4618 + Amlo
Started	6	6	6	6
Completed	6	6	5	6
Not completed	0	0	1	0
Withdrew: Withdrawal by subject	0	0	1	0

Outcome measures

PrimaryPercentage of Participants With a Clinical or Laboratory Adverse Experience

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.

Time frame:: Up to 42 days
Reported as:: Number · Percentage of participants

Percentage of Participants With a Clinical or Laboratory Adverse Experience
Percentage of participants	Panel A: MK-4618 + Met	Panel A: PBO + Met	Panel B: MK-4618 + Amlo	Panel B: PBO + Amlo
Percentage of Participants With a Clinical or Laboratory Adverse Experience	33.3	53.8	41.7	61.5

PrimaryMaximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A

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.

Time frame:: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7
Reported as:: Mean · mmHg

Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
mmHg	Panel A: MK-4618 + Met	Panel A: PBO + Met
Semi-recumbent, Day 1	16.03 (9.46 to 22.61)	17.25 (10.93 to 23.57)
Semi-recumbent, Day 7	14.38 (7.81 to 20.96)	12.10 (5.78 to 18.42)
Standing, Day 1	14.79 (7.43 to 22.15)	13.14 (6.01 to 20.26)
Standing, Day 7	6.12 (-1.24 to 13.49)	7.21 (0.09 to 14.34)

Statistical analysis

Panel A: MK-4618 + Met vs Panel A: PBO + Met · Mean difference (final values): -1.22 · 90% CI -8.42 to 5.98The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.
Panel A: MK-4618 + Met vs Panel A: PBO + Met · Mean difference (final values): 2.29 · 90% CI -4.92 to 9.49The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.
Panel A: MK-4618 + Met vs Panel A: PBO + Met · Mean difference (final values): 1.65 · 90% CI -5.31 to 8.62The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.
Panel A: MK-4618 + Met vs Panel A: PBO + Met · Mean difference (final values): -1.09 · 90% CI -8.06 to 5.88The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.

PrimaryMaximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B

Time frame:: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7
Reported as:: Mean · mmHg

Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
mmHg	Panel B: MK-4618 + Amlo	Panel B: PBO + Amlo
Semi-recumbent, Day 1	14.69 (9.65 to 19.72)	12.74 (7.87 to 17.61)
Semi-recumbent, Day 7	10.52 (5.48 to 15.55)	16.43 (11.56 to 21.30)
Standing, Day 1	6.50 (1.27 to 11.73)	12.75 (7.70 to 17.79)
Standing, Day 7	6.33 (1.10 to 11.57)	7.90 (2.85 to 12.95)

Statistical analysis

Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo · Mean difference (final values): 1.95 · 90% CI -2.85 to 6.75The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.
Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo · Mean difference (final values): -5.91 · 90% CI -10.71 to -1.11The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.
Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo · Mean difference (final values): -6.25 · 90% CI -11.47 to -1.03The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.
Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo · Mean difference (final values): -1.57 · 90% CI -6.79 to 3.65The estimated parameter is mean maximum change from baseline for placebo minus MK-4618. Mean and confidence interval for the difference were obtained from linear mixed effects model performed on the maximum increase from baseline values.

SecondarySteady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618

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.

Time frame:: Predose and up to 24 hours postdose on Day 7
Reported as:: Geometric mean · uM*hr

Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618
uM*hr	Panel A: MK-4618 + Met	Panel B: MK-4618 + Amlo
Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618	2.60 (2.09 to 3.24)	4.60 (3.69 to 5.74)

Adverse events

Collected over Up to 42 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Panel A: MK-4618 + Met	—	0/12 (0%)	4/12 (33.3%)
Panel A: PBO + Met	—	0/13 (0%)	7/13 (53.8%)
Panel B: MK-4618 + Amlo	—	0/12 (0%)	5/12 (41.7%)
Panel B: PBO + Amlo	—	0/13 (0%)	8/13 (61.5%)

Most frequent other events

Showing 10 of 22

Most frequent other events
Event	Panel A: MK-4618 + Met	Panel A: PBO + Met	Panel B: MK-4618 + Amlo	Panel B: PBO + Amlo
HeadacheNervous system disorders	1/12	5/13	2/12	2/13
Abdominal pain lowerGastrointestinal disorders	0/12	0/13	1/12	0/13
ToothacheGastrointestinal disorders	0/12	0/13	1/12	0/13
Vessel puncture site swellingGeneral disorders	0/12	0/13	1/12	0/13
Pain in extremityMusculoskeletal and connective tissue disorders	1/12	0/13	0/12	1/13
DysuriaRenal and urinary disorders	0/12	0/13	1/12	0/13
Penile painReproductive system and breast disorders	1/12	0/13	0/12	0/13
FlushingVascular disorders	1/12	0/13	0/12	0/13
Hot flushVascular disorders	1/12	0/13	0/12	0/13
AnaemiaBlood and lymphatic system disorders	0/12	1/13	0/12	0/13

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Panel A Participants	Panel B Participants	Total
Mean	53.8 (42 to 68)	55.2 (41 to 77)	54.5 (41 to 77)

Sex: Female, Male
Sex: Female, Male(Participants)	Panel A Participants	Panel B Participants	Total
Female	4	8	12
Male	9	5	14

Study locations

No study locations are listed for this record.

References and documents

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 24, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01337674
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Apr 19, 2011
Start date: Apr 1, 2011
Primary completion: Nov 1, 2011
Completion: Nov 1, 2011
Results posted: Feb 2, 2016
Last update: Dec 24, 2018

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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