A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009)

NCT01370655 | Completed Phase 1 Results

• 1 other identifier: 7145-009
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being done to evaluate the antihypertensive efficacy and tolerability of MK-7145 in participants with mild-to-moderate hypertension. The primary hypotheses for the study were as follows:

1. 1.Multiple dose administration of 6-mg MK-7145 results in a reduction in systolic blood pressure (SBP) in male participants with mild to moderate hypertension that is superior to placebo, as measured by time weighted average change from baseline over 24 hours postdose (TWA0-24hrs) on dosing Day 28
2. 2.Multiple dose administration of 6-mg MK-7145 results in a reduction in SBP in male participants with mild to moderate hypertension that is similar to hydrochlorothiazide (HCTZ), as measured by TWA0-24hrs on dosing Day 28
3. 3.The effect of MK-7145 and HCTZ on natriuresis (UNaV) as well as SBP and diastolic blood pressure (DBP), both as measured by TWA0-24hrs, will be estimated
4. 4.Multiple dose administration of MK-7145 for 4 weeks will be generally safe and well-tolerated.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP)

  Each participant had their blood pressure monitored by continuous 24-hour ambulatory blood pressure monitoring (ABPM) on Days -1 and 28 of each treatment period. The average systolic blood pressure over the 24-hour monitoring period was calculated for baseline (Day -1) and Day 28. The difference between baseline and Day 28 was calculated and recorded.

  Baseline and Day 28

• Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Diastolic Blood Pressure (DBP)

  Each participant had their blood pressure monitored by continuous 24-hour ambulatory blood pressure monitoring (ABPM) on Days -1 and 28 of each treatment period. The average diastolic blood pressure over the 24-hour monitoring period was calculated for baseline (Day -1) and Day 28. The difference between baseline and Day 28 was calculated and recorded.

  Baseline and Day 28

• Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1

  Urine sodium (Na) levels were measured over 24-hours on Day -1 (baseline) and on Day 1. The total amount of Na excreted in the urine for Day-1 (baseline) and Day1 were calculated and the difference between the 2 values was recorded.

  Baseline (Day-1) and Day 1

• Percentage of Participants Who Experienced at Least 1 Adverse Event (AE)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced an AE during the study was summarized by study drug taken at the time of the AE.

  Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)

• Percentage of Participants Who Had Study Discontinued During the Study Due to an Adverse Event (AE)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had the administration of the study drug discontinued during the study was summarized by study drug taken at the time of the AE. Participants may or may not have completed the study.

  up to 4 weeks of each treatment period

• Percentage of Participants Who Experienced at Least 1 Drug-related Adverse Event (AE)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced an AE that was reported as at least possibly-related to the study was summarized by study drug taken at the time of the AE.

  Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)

Secondary Outcomes (1)

• Change From Baseline in Urine Potassium at 24 Hours Post-dose on Day 28

  Baseline (Day -1) and Day 28

Study Arms (4)

MK-7145 6 mg (Treatment A)

EXPERIMENTAL

MK-7145 3 mg (three x 1-mg MK-7145 capsules administered orally) and placebo to HCTZ (two 12.5-mg capsules) then three x 1-mg MK-7145 capsules 4 hours later, daily for 4 weeks.

Drug: MK-7145; Drug: Placebo to HCTZ

MK-7145 3 mg (Treatment B)

EXPERIMENTAL

MK-7145 3 mg (one 2mg MK-7145 and one MK-7145 placebo capsule) then one 1-mg MK-7145 capsule and two MK-7145 placebo capsules 4 hours later and placebo to HCTZ (2 capsules once daily) daily for 4 weeks.

Drug: MK-7145; Drug: Placebo to MK-7145; Drug: Placebo to HCTZ

Hydrochlorothiazide 25 mg (Treatment C)

ACTIVE COMPARATOR

HCTZ 25 mg (two 12.5-mg capsules) and placebo to MK-7145 (one 3-mg capsule) then placebo for MK-7145 (one 3-mg capsule) 4 hours later daily for 4 weeks.

Drug: Hydrochlorothiazide (HCTZ); Drug: Placebo to MK-7145

Placebo (Treatment D)

PLACEBO COMPARATOR

Placebo to MK-7145 (2 x 3-mg capsules) and placebo to HCTZ 25 mg (2 capsules) then placebo to MK-7145 (2 x 3-mg capsules) 4 hours later daily for 4 weeks

Drug: Placebo to MK-7145; Drug: Placebo to HCTZ

Interventions

MK-7145 DRUG

MK-7145 3 mg (Treatment B); MK-7145 6 mg (Treatment A)

Hydrochlorothiazide (HCTZ) DRUG

Hydrochlorothiazide 25 mg (Treatment C)

Placebo to MK-7145 DRUG

Hydrochlorothiazide 25 mg (Treatment C); MK-7145 3 mg (Treatment B); Placebo (Treatment D)

Placebo to HCTZ DRUG

MK-7145 3 mg (Treatment B); MK-7145 6 mg (Treatment A); Placebo (Treatment D)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of essential hypertension
• Body mass index (BMI) ≤35 kg/m\^2
• Participant in general good health
• No history of clinically significant arrhythmias or clinically significant abnormality on electrocardiogram (ECG)
• No history of clinically significant cardiac disease
• Treatment-naïve or taking up to 2 antihypertensive therapeutic agents
• Non-smoker and/or has not used nicotine or nicotine-containing products for at least 6 months

You may not qualify if:

• Participant has low plasma potassium
• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of osteoporosis
• Active or history of nephrocalcinosis, nephrolithiasis or hypercalciuria
• Orthostatic change in vital sign measurements while going from a semi-recumbent to standing position accompanied by symptoms
• Functional disability that can interfere with rising from a semi-recumbent position to the standing position
• History of malignant neoplastic disease. Exceptions: (1) adequately treated non-melanomatous skin carcinoma; (2) other malignancies which have been successfully treated \>10 years prior to the prestudy (screening) visit, (3) unlikely to sustain a recurrence
• Participant is unable to refrain from the use of prescription and non-prescription drugs such as high-dose aspirin (≥325 mg/day), strong/moderate Cytochrome P450 3A4 (CYP3A4) inhibitors (such as ritonavir, indinavir, nelfinavir, erythromycin, telithromycin, clarithromycin, chloramphenicol, fluconazole, ketoconazole, itraconazole, nefazodone, aprepitant, verapamil, or diltiazem) as well as strong/moderate CYP3A4 inducers (such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, efavirenz, nevirapine, etravirine, rifampicin, modafinil, St Johns Wort, cyproterone, or progestin) beginning approximately 2 weeks (or 5 half-lives), prior to administration of the initial dose of study drug until the post study visit
• Current use of non-steroidal anti-inflammatory drugs (NSAIDs) other than low dose aspirin, aluminum- or magnesium-containing antacids, sucralfate, metal cations such as iron, multivitamins containing iron or zinc that cannot be discontinued at least 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug until the post study visit
• Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) per day
• Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Major surgery, donation or lost 1 unit of blood (approximately 500 mL), or participation in another investigational study within 4 weeks prior to the prestudy (screening)
• History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Regular use of any illicit drugs or history of drug abuse within approximately 6 months

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Interventions

MK-7145; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 10, 2011
• Study Start: June 15, 2011
• Primary Completion: December 19, 2011
• Study Completion: January 26, 2012
• Last Updated: September 21, 2018
• Results First Posted: April 4, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share