NCT01370655

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

Completed Phase 1 Results posted Last updated 21 September 2018

What this trial tests

Phase 1 trial testing MK-7145 in Hypertension in 46 participants. Completed in 26 January 2012.

Timeline

15 June 2011

Primary endpoint
19 December 2011

26 January 2012

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	46
Start date	15 June 2011
Primary completion	19 December 2011
Estimated completion	26 January 2012

Drugs / interventions tested

• MK-7145 — full drug profile →
• Hydrochlorothiazide (HCTZ) — full drug profile →
• Placebo to MK-7145 — full drug profile →
• Placebo to HCTZ — full drug profile →

Conditions studied

• Hypertension — all drugs for Hypertension →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 75, male only, with Hypertension. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP) Primary · Baseline and Day 28

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.

Group	Value	95% CI
MK-7145 3 mg	-9.5	-12.7 – -6.4
MK-7145 6 mg	-10.2	-12.8 – -7.6
HCTZ 25 mg	-4.8	-7.6 – -1.9
Placebo	-2.8	-6.1 – 0.4

Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Diastolic Blood Pressure (DBP) Primary · Baseline and Day 28

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.

Group	Value	95% CI
MK-7145 3 mg	-4.5	-6.7 – -2.3
MK-7145 6 mg	-4.3	-6.2 – -2.5
HCTZ 25 mg	-1.5	-3.5 – 0.6
Placebo	-1.1	-3.4 – 1.2

Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1 Primary · Baseline (Day-1) and 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.

Group	Value	95% CI
MK-7145 3 mg	0.4	-31.0 – 31.7
MK-7145 6 mg	46.0	20.3 – 71.7
HCTZ 25 mg	64.1	36.6 – 91.6
Placebo	-30.5	-61.0 – -0.1

Percentage of Participants Who Experienced at Least 1 Adverse Event (AE) Primary · Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)

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.

Group	Value	95% CI
MK-7145 3 mg	84.2
MK-7145 6 mg	78.6
HCTZ 25 mg	73.1
Placebo	47.4

Percentage of Participants Who Had Study Discontinued During the Study Due to an Adverse Event (AE) Primary · up to 4 weeks of each treatment period

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 m

Group	Value	95% CI
MK-7145 3 mg	0
MK-7145 6 mg	10.7
HCTZ 25 mg	7.7
Placebo	5.3

Percentage of Participants Who Experienced at Least 1 Drug-related Adverse Event (AE) Primary · Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)

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.

Group	Value	95% CI
MK-7145 3 mg	52.6
MK-7145 6 mg	42.9
HCTZ 25 mg	42.3
Placebo	26.3

Change From Baseline in Urine Potassium at 24 Hours Post-dose on Day 28 Secondary · Baseline (Day -1) and Day 28

Urine potassium (K+) levels were measured over 24-hours on Day -1 and on Day 28. The total amount of K+ excreted in the urine for Day-1 (baseline) and Day 28 were calculated and the difference between the 2 values was recorded.

Group	Value	95% CI
MK-7145 3 mg	0.3	-9.2 – 9.8
MK-7145 6 mg	-6.5	-14.3 – 1.3
HCTZ 25 mg	-2.7	-11.3 – 6.0
Placebo	-7.6	-17.4 – 2.2

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 14 days post last dose of study drug for each treatment period. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MK-7145 3 mg

Serious: 0/19 (0%)

Deaths: —

MK-7145 6 mg

Serious: 1/28 (4%)

Deaths: —

HCTZ 25 mg

Serious: 2/26 (8%)

Deaths: —

Placebo

Serious: 0/19 (0%)

Deaths: —

Serious adverse events (3 terms)

Reaction	System	MK-7145 3 mg	MK-7145 6 mg	HCTZ 25 mg	Placebo
Arrhythmia	Cardiac disorders	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (30 terms — click to expand)

Reaction	System	MK-7145 3 mg	MK-7145 6 mg	HCTZ 25 mg	Placebo
Headache	Nervous system disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Blood uric acid increased	Investigations	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Thirst	General disorders	—	—	—	—
Vision blurred	Eye disorders	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Blood potassium decreased	Investigations	—	—	—	—
Blood pressure systolic increased	Investigations	—	—	—	—
Weight decreased	Investigations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Presyncope	Nervous system disorders	—	—	—	—
Polyuria	Renal and urinary disorders	—	—	—	—
Palpitations	Cardiac disorders	—	—	—	—
Eye pain	Eye disorders	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Blood aldosterone increased	Investigations	—	—	—	—
Glycosuria	Renal and urinary disorders	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—
Erectile dysfunction	Reproductive system and breast disorders	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Nocturnal dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: Arrhythmia, Migraine, Asthma.

Data from ClinicalTrials.gov NCT01370655 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. New developments in the pharmacological treatment of hypertension: dead-end or a glimmer at the horizon?
   Paulis L, Rajkovicova R, Simko F. · · 2015 · cited 23× · PMID 25893478 · DOI 10.1007/s11906-015-0557-x