HypertensionPhase 1NCT01446003

A Study of the Effect of MK-8457 on Blood Pressure in Hypertensive Participants (MK-8457-004-AM1)

A Phase 1 study testing MK-8457 in people with Hypertension, run by Merck Sharp & Dohme LLC at 2 sites in United States.

Completed

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

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Hypertension
What is being tested?: MK-8457
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 2 sitesUnited States
Study dates: 25 Oct 2011to 3 Mar 2012
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

If female, must be of non-childbearing potential
If male with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
Body mass index (BMI) ≤35 kg/m^2
Mild-to-moderate hypertension requiring treatment with one or more antihypertensive agents
Receiving stable treatment for hypertension for at least 8 weeks prior to the start of dosing and continuing therapy for duration of study
No clinically significant arrhythmias or clinically significant abnormality on electrocardiogram
Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Who cannot join

Any illness that might confound the results of the study or poses an additional risk
History of stroke, chronic seizures, or major neurological disorder
Clinically significant endocrine, gastrointestinal, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
Clinically significant cardiovascular disease or has active angina
History of malignant neoplastic disease
Taking 325 mg aspirin daily

Show all 12Show fewer

Taking 3 or more medications for the treatment of hypertension
Unable to refrain from or anticipates the use of any non-steroidal anti-inflammatory drugs (NSAIDs)
Consumes excessive amounts of alcohol and/or coffee, tea, cola, or other caffeinated beverages
Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
Significant multiple and/or severe allergies
Regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years

Trial locations and contacts

2 sites in 1 country.

United States2 sites

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Miramar, Florida
Call for Information
Tacoma, Washington

Other trials in United States

About this study

Official title: A Multiple-Dose Clinical Trial to Study the Effect of MK-8457 on Ambulatory Blood Pressure in Hypertensive Patients

This study will evaluate the effect of treatment with multiple doses of MK-8457 on systolic blood pressure in participants with mild to moderate hypertension in addition to safety and tolerability. The study hypothesis is that MK-8457 does not increase systolic blood pressure to a clinically significant extent, as measured by 24-hour mean ambulatory systolic blood pressure change from baseline after 10 days of dosing.

Conditions: Hypertension
Being tested: MK-8457, Placebo for MK-8457
Medical subject headings: Hypertension

What participants receive

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

MK-8457Drug
10 x 10-mg capsule BID for 10 days
Placebo for MK-8457Drug
10 x 10-mg capsule BID for 10 days

Study groups in NCT01446003
Study group	Role	What they receive
MK-8457-Placebo Sequence	Experimental	Participants received MK-8457 100 mg twice daily (BID) for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout. Receives: Drug: MK-8457; Drug: Placebo for MK-8457
Placebo-MK-8457 Sequence	Experimental	Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout. Receives: Drug: MK-8457; Drug: Placebo for MK-8457

What is being measured

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

Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)
SBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour least squares (LS) mean ambulatory SBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour SBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.
Measured: Baseline and Day 10
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 70 days
Number of Participants Who Discontinued the Study Medication Due to an AE
An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 70 days

Secondary outcomes (6)

Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)
DBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour LS mean ambulatory DBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour DBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.
Measured: Baseline and Day 10
Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours
The effect of drug on resting blood pressure was estimated using maxMAΔ. The maxMAΔ in blood pressure was calculated as the maximum moving average change from baseline to Day 10 of 3 consecutive 15-minute blood pressure measurements across the first 4 hours after the morning (AM) and evening (PM) doses. In this method, the LS means of three consecutive time points over the 4 hour period were determined and the maximum LS mean was used for the endpoint. Blood pressure was determined using continuous monitoring at rest. Increased values represent an increase in hypertensive severity.
Measured: Up to 4 hours postdose on Days 1 and 10
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457
AUC0-12hr is an estimate of total plasma exposure to study drug over the dosing interval (12hr). Plasma concentrations of MK-8457 were determined on Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group is not included; this endpoint evaluated only the MK-8457 group.
Measured: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10
Maximum Concentration (Cmax) of MK-8457
Maximum plasma concentrations of MK-8521 were determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.
Measured: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10
Time to Maximum Concentration (Tmax) of MK-8457
Tmax was determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.
Measured: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10
Trough Plasma Concentration (Ctrough) of MK-8457
The lowest plasma concentration reached by the drug prior to the next administration was determined for Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group was not included; this endpoint evaluated only the MK-8457 group.
Measured: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; pre-AM dose on Day 5 or 6

Timeline

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

25 Oct 20113 Mar 2012

First posted4 Oct 2011 (estimated)
Study start25 Oct 2011
Primary completion18 Feb 2012
Study completion3 Mar 2012

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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01446003
Sponsor's protocol ID: 8457-004
Status last verified: Jan 2019
First submitted: 30 Sep 2011
Last updated: 5 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/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?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple-Dose Clinical Trial to Study the Effect of MK-8457 on Ambulatory Blood Pressure in Hypertensive Patients
ClinicalTrials.gov ID: NCT01446003
Acronym / sponsor ID: 8457-004
Conditions: Hypertension
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 25 Oct 2011 (actual)
Primary completion: 18 Feb 2012 (actual)
Study completion: 3 Mar 2012 (actual)
First posted: 4 Oct 2011 (estimated)
Results: Posted 2 May 2017

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: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
MK-8457-Placebo Sequence	Experimental	Drug: MK-8457, Drug: Placebo for MK-8457Participants received MK-8457 100 mg twice daily (BID) for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.
Placebo-MK-8457 Sequence	Experimental	Drug: MK-8457, Drug: Placebo for MK-8457Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

If female, must be of non-childbearing potential
If male with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
Body mass index (BMI) ≤35 kg/m^2
Mild-to-moderate hypertension requiring treatment with one or more antihypertensive agents
Receiving stable treatment for hypertension for at least 8 weeks prior to the start of dosing and continuing therapy for duration of study

Key exclusion criteria (12 listed)

Any illness that might confound the results of the study or poses an additional risk
History of stroke, chronic seizures, or major neurological disorder
Clinically significant endocrine, gastrointestinal, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
Clinically significant cardiovascular disease or has active angina
History of malignant neoplastic disease

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-845710 x 10-mg capsule BID for 10 days	Drug	MK-8457-Placebo Sequence, Placebo-MK-8457 Sequence
Placebo for MK-845710 x 10-mg capsule BID for 10 days	Drug	MK-8457-Placebo Sequence, Placebo-MK-8457 Sequence

Primary outcome

Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)
Time frame: Baseline and Day 10
SBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour least squares (LS) mean ambulatory SBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour SBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.
Number of Participants Who Experienced at Least One Adverse Event (AE)
Time frame: Up to 70 days
An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Who Discontinued the Study Medication Due to an AE
Time frame: Up to 70 days
An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

6 secondary outcomes

Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)
Time frame: Baseline and Day 10
Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours
Time frame: Up to 4 hours postdose on Days 1 and 10
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457
Time frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10
Maximum Concentration (Cmax) of MK-8457
Time frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10
Time to Maximum Concentration (Tmax) of MK-8457
Time frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10
Trough Plasma Concentration (Ctrough) of MK-8457
Time frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; pre-AM dose on Day 5 or 6

Results and safety

Results posted to the registry on 2 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-8457-Placebo Sequence	16	14
Placebo-MK-8457 Sequence	15	15

Primary outcome: Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)

Time frame: Baseline and Day 10. Least squares mean (95% Confidence Interval). Unit: mmHg

Measure	MK-8457 100 mg BID n = 29	Placebo n = 28
Value	-0.47 (-2.60 to 1.66)	-2.49 (-4.66 to -0.31)

MK-8457 100 mg BID vs Placebo: Mean Difference (Final Values): 2.02 (90% CI -0.52 to 4.56), Linear mixed effect models

Population analysed: The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (change in 24-hour mean ambulatory SBP).

Primary outcome: Number of Participants Who Experienced at Least One Adverse Event (AE)

Time frame: Up to 70 days. Number. Unit: Participant

Measure	MK-8457 100 mg BID n = 31	Placebo n = 29
Value	8 (-2.60 to 1.66)	9 (-4.66 to -0.31)

Population analysed: The safety population consisted of all participants who received at least one dose of the investigational drug.

Primary outcome: Number of Participants Who Discontinued the Study Medication Due to an AE

Time frame: Up to 70 days. Number. Unit: Participant

Measure	MK-8457 100 mg BID n = 31	Placebo n = 29
Value	1 (-2.60 to 1.66)	0 (-4.66 to -0.31)

Population analysed: The safety population consisted of all participants who received at least one dose of the investigational drug.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 70 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-8457 100 mg BID	0 of 31 (0%)	8 of 31 (25.8%)	Not reported
Placebo	0 of 29 (0%)	9 of 29 (31%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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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

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-8457 in people with Hypertension, run by Merck Sharp & Dohme LLC at 2 sites in United States.

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 7 inclusion and 12 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 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 May 2017). 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?

Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP) (time frame: Baseline and Day 10). 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 NCT01446003.

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 5 Feb 2019.