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Completed

NCT Number: NCT01446003

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

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.

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Key information

Conditions

Hypertension Cardiovascular Diseases Vascular Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Call for Information, Miramar, Florida, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

MK-8457

Drug

10 x 10-mg capsule BID for 10 days

Placebo for MK-8457

Drug

10 x 10-mg capsule BID for 10 days

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)

    Time frame: Baseline and Day 10

    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.

  2. 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

    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.

  3. 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

    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.

  4. 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

    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.

  5. 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

    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.

  6. 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

    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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Oct 4, 2011
Registry last updated
Feb 5, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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