Phase 1 Completed N=46 Randomized Double-blind Treatment

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

Source: ClinicalTrials.gov NCT01370655 ↗

Enrolled (actual)

Serious AEs

3.3%

Results posted

Apr 2017

Primary outcomePrimary: Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP) — -9.5; -10.2; -4.8; -2.8 mmHg

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP)	-9.5; -10.2; -4.8; -2.8	—
PRIMARY Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Diastolic Blood Pressure (DBP)	-4.5; -4.3; -1.5; -1.1	—
PRIMARY Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1	0.4; 46.0; 64.1; -30.5	—
PRIMARY Percentage of Participants Who Experienced at Least 1 Adverse Event (AE)	84.2; 78.6; 73.1; 47.4	—
PRIMARY Percentage of Participants Who Had Study Discontinued During the Study Due to an Adverse Event (AE)	0; 10.7; 7.7; 5.3	—
PRIMARY Percentage of Participants Who Experienced at Least 1 Drug-related Adverse Event (AE)	52.6; 42.9; 42.3; 26.3	—
SECONDARY Change From Baseline in Urine Potassium at 24 Hours Post-dose on Day 28	0.3; -6.5; -2.7; -7.6	—

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

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Data sourced from ClinicalTrials.gov (NCT01370655). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.