Clinical trial NCT01370655: A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009)
Official title: A Phase Ib, Randomized, Double-Blind, 4-Treatment, 2-Period Incomplete Block Study to Evaluate the Multiple Dose Effects of MK-7145 and Hydrochlorothiazide Compared to Placebo on Blood Pressure in Male Patients With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-06-10
Enrollment: 46
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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. 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. 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. 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. Multiple dose administration of MK-7145 for 4 weeks will be generally safe and well-tolerated.


Eligibility criteria: Inclusion criteria:

* 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

Exclusion criteria:

* 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
* Dehydration or volume-depletion

Primary outcomes:
measure: Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP)
timeFrame: Baseline and Day 28
measure: Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Diastolic Blood Pressure (DBP)
timeFrame: Baseline and Day 28
measure: Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1
timeFrame: Baseline (Day-1) and Day 1
measure: Percentage of Participants Who Experienced at Least 1 Adverse Event (AE)
timeFrame: Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)
measure: Percentage of Participants Who Had Study Discontinued During the Study Due to an Adverse Event (AE)
timeFrame: up to 4 weeks of each treatment period
measure: Percentage of Participants Who Experienced at Least 1 Drug-related Adverse Event (AE)
timeFrame: Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)
Secondary outcomes:
measure: Change From Baseline in Urine Potassium at 24 Hours Post-dose on Day 28
timeFrame: Baseline (Day -1) and Day 28
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: