HypertensionPhase 1NCT01337674

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

A Phase 1 study testing MK-4618, Metoprolol and Amlodipine in people with Hypertension, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Hypertension
What is being tested?: MK-4618, Metoprolol and Amlodipine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: No sites listed yet
Study dates: 1 Apr 2011to 1 Nov 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

Official title: A Study to Evaluate the Co-Administration of MK-4618 With Antihypertensive Agents

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: Hypertension
Being tested: MK-4618, Placebo for MK-4618, Metoprolol, Amlodipine
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-4618Drug
Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7
Placebo for MK-4618Drug
Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7
MetoprololDrug
Also called Toprol-XL
Previously prescribed daily dose of open-label metoprolol for the duration of the study
AmlodipineDrug
Also called Norvasc
Previously prescribed daily dose of open-label amlodipine for the duration of the study

Study groups in NCT01337674
Study group	Role	What they receive
Panel A: MK-4618 + Met → PBO + Met	Experimental	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. Receives: Drug: MK-4618; Drug: Placebo for MK-4618; Drug: Metoprolol
Panel A: PBO + Met → MK-4618 + Met	Experimental	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. Receives: Drug: MK-4618; Drug: Placebo for MK-4618; Drug: Metoprolol
Panel B: MK-4618 + Amlo → PBO + Amlo	Experimental	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. Receives: Drug: MK-4618; Drug: Placebo for MK-4618; Drug: Amlodipine
Panel B: PBO + Amlo → MK-4618 + Amlo	Experimental	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. Receives: Drug: MK-4618; Drug: Placebo for MK-4618; Drug: Amlodipine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7

Secondary outcomes (1)

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.
Measured: Predose and up to 24 hours postdose on Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Apr 20111 Nov 2011

First posted19 Apr 2011 (estimated)
Study start1 Apr 2011
Primary completion1 Nov 2011
Study completion1 Nov 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HypertensionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01337674
Sponsor's protocol ID: 4618-010
Status last verified: Dec 2018
First submitted: 15 Apr 2011
Last updated: 24 Dec 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension

All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Evaluate the Co-Administration of MK-4618 With Antihypertensive Agents
ClinicalTrials.gov ID: NCT01337674
Acronym / sponsor ID: 4618-010
Conditions: Hypertension
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 1 Apr 2011 (actual)
Primary completion: 1 Nov 2011 (actual)
Study completion: 1 Nov 2011 (actual)
First posted: 19 Apr 2011 (estimated)
Results: Posted 2 Feb 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Panel A: MK-4618 + Met → PBO + Met	Experimental	Drug: MK-4618, Drug: Placebo for MK-4618, Drug: MetoprololOnce 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	Experimental	Drug: MK-4618, Drug: Placebo for MK-4618, Drug: MetoprololOnce 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	Experimental	Drug: MK-4618, Drug: Placebo for MK-4618, Drug: AmlodipineOnce 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	Experimental	Drug: MK-4618, Drug: Placebo for MK-4618, Drug: AmlodipineOnce 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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-4618Once daily oral dose of MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7	Drug	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
Placebo for MK-4618Once daily oral dose of placebo for MK-4618 100 mg (two 50 mg tablets) on Days 1 through 7	Drug	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
MetoprololAlso: Toprol-XLPreviously prescribed daily dose of open-label metoprolol for the duration of the study	Drug	Panel A: MK-4618 + Met → PBO + Met, Panel A: PBO + Met → MK-4618 + Met
AmlodipineAlso: NorvascPreviously prescribed daily dose of open-label amlodipine for the duration of the study	Drug	Panel B: MK-4618 + Amlo → PBO + Amlo, Panel B: PBO + Amlo → MK-4618 + Amlo

Primary outcome

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

1 secondary outcome

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

Results and safety

Results posted to the registry on 2 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Panel A: MK-4618 + Met → PBO + Met	6	6
Panel A: PBO + Met → MK-4618 + Met	7	6
Panel B: MK-4618 + Amlo → PBO + Amlo	6	6
Panel B: PBO + Amlo → MK-4618 + Amlo	7	6

Primary outcome: Percentage of Participants With a Clinical or Laboratory Adverse Experience

Time frame: Up to 42 days. Number. Unit: Percentage of participants

Measure	Panel A: MK-4618 + Met n = 12	Panel A: PBO + Met n = 13	Panel B: MK-4618 + Amlo n = 12	Panel B: PBO + Amlo n = 13
Value	33.3	53.8	41.7	61.5

Population analysed: The All Subjects as Treated population included all participants who received \>=1 dose of study drug

Primary outcome: Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A

Time frame: Baseline (predose) and up to 24 hours postdose on Day 1 and Day 7. Mean (95% Confidence Interval). Unit: mmHg

Measure	Panel A: MK-4618 + Met n = 12	Panel A: PBO + Met n = 13
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)

Panel A: MK-4618 + Met vs Panel A: PBO + Met: Mean Difference (Final Values): -1.22 (90% CI -8.42 to 5.98)
Panel A: MK-4618 + Met vs Panel A: PBO + Met: Mean Difference (Final Values): 2.29 (90% CI -4.92 to 9.49)
Panel A: MK-4618 + Met vs Panel A: PBO + Met: Mean Difference (Final Values): 1.65 (90% CI -5.31 to 8.62)

Population analysed: The All Subjects as Treated population included all participants who received \>=1 dose of study drug.

Primary outcome: Maximum 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. Mean (95% Confidence Interval). Unit: mmHg

Measure	Panel B: MK-4618 + Amlo n = 12	Panel B: PBO + Amlo n = 13
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)

Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo: Mean Difference (Final Values): 1.95 (90% CI -2.85 to 6.75)
Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo: Mean Difference (Final Values): -5.91 (90% CI -10.71 to -1.11)
Panel B: MK-4618 + Amlo vs Panel B: PBO + Amlo: Mean Difference (Final Values): -6.25 (90% CI -11.47 to -1.03)

Population analysed: The All Subjects as Treated population included all participants who received \>=1 dose of study drug.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 42 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Panel A: MK-4618 + Met	0 of 12 (0%)	4 of 12 (33.3%)	Not reported
Panel A: PBO + Met	0 of 13 (0%)	7 of 13 (53.8%)	Not reported
Panel B: MK-4618 + Amlo	0 of 12 (0%)	5 of 12 (41.7%)	Not reported
Panel B: PBO + Amlo	0 of 13 (0%)	8 of 13 (61.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Hypertension

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-4618, Metoprolol and Amlodipine in people with Hypertension, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With a Clinical or Laboratory Adverse Experience (time frame: Up to 42 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01337674.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2018.