Phase 1
N=30
A Multiple Dose Study of MK-3614 (MK-3614-002)
Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT01033643 ↗Enrolled (actual)
30
Serious AEs
0.0%
Results posted
May 2021
Primary outcome: Primary: Number of Participants Who Experienced an Adverse Event (AE) — 4; 3; 4; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-3614 (Drug); Placebo for MK-3614 (Drug)
- Age
- Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Dec 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced an Adverse Event (AE) |
4; 3; 4; 3; 3 | — |
| PRIMARY Number of Participants Who Discontinued Study Treatment Due to an AE |
0; 0; 0; 0; 0 | — |
| PRIMARY Panel A: Area Under the Concentration Time-Curve From 0 to 12 Hours (AUC 0-12hrs) of MK-3614 |
43.9; 105.0 | — |
| PRIMARY Panel D: Area Under the Concentration Time-Curve From 0 to 12 Hours (AUC 0-12hrs) of MK-3614 |
87.8; 144.0 | — |
| PRIMARY Panel D: Area Under the Concentration Time-Curve From 0 to Infinity (AUC 0-inf) of MK-3614 |
— | — |
| PRIMARY Panels B, C: Area Under the Concentration Time-Curve From 0 to 24 Hours (AUC 0-24hrs) of MK-3614 |
188.0; 190.0; 335.0; 302.0 | — |
| PRIMARY Panel A: Maximum Concentration (Cmax) of MK-3614 |
5.61; 11.6 | — |
| PRIMARY Panel D: Maximum Concentration (Cmax) of MK-3614 |
11.6; 16.1 | — |
| PRIMARY Panels B, C: Maximum Concentration (Cmax) of MK-3614 |
12.2; 11.1; 19.0; 18.5 | — |
| PRIMARY Panel A: Time to Maximum Concentration (Tmax) of MK-3614 |
4.0; 4.0 | — |
| PRIMARY Panel D: Time to Maximum Concentration (Tmax) of MK-3614 |
4.5; 4.5 | — |
| PRIMARY Panels B, C: Time to Maximum Concentration (Tmax) of MK-3614 |
4.0; 11.0; 6.0; 4.0 | — |
| PRIMARY Panels A, B & C: Apparent Terminal Half-Life (t1/2) of MK-3614 |
10.1; 12.7; 11.9 | — |
| PRIMARY Panel D: Apparent Terminal Half-Life (t1/2) of MK-3614 |
8.1 | — |
| PRIMARY Change From Baseline in Aortic Augmentation Index (AIx) at 24 Hours Postdose After Multiple Doses of MK-3614 or Placebo |
-9.94; -1.0; -9.25; -2.25; -5.78 | — |
| PRIMARY Time-weighted Average Across 12 Hours (TWA 0-12hrs) for Heart Rate (HR) After Administration of MK-3614 or Placebo |
62.15; 63.58; 63.04; 69.84; 66.80; 70.18 | — |
| SECONDARY Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Systolic Blood Pressure (SBP) on First Day of Multiple Dosing of MK-3614 or Placebo |
-9.47; -15.19; -14.36; -5.57; -5.88 | — |
| SECONDARY Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Systolic Blood Pressure (SBP) on Last Day After Multiple Dosing of MK-3614 or Placebo |
-10.25; -19.33; -15.61; -14.05; -8.29 | — |
| SECONDARY Change From Baseline in Time-Weighted Average Across 24 Hours (TWA 0-24hrs) of Peripheral Systolic Blood Pressure (SBP) on Last Day of Multiple Dosing of MK-3614 or Placebo |
-11.37; -18.59; -17.66; -15.43; -9.15 | — |
| SECONDARY Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Diastolic Blood Pressure (DBP) on First Day of Multiple Dosing of MK-3614 or Placebo |
-8.32; -13.18; -9.85; -3.97; -3.17 | — |
| SECONDARY Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Diastolic Blood Pressure (DBP) on Last Day of Multiple Dosing of MK-3614 or Placebo |
-10.81; -15.43; -10.50; -8.58; -3.43 | — |
| SECONDARY Change From Baseline in Time-Weighted Average Across 24 Hours (TWA 0-24hrs) of Peripheral Diastolic Blood Pressure (DBP) on Last Day of Multiple Dosing of MK-3614 or Placebo |
-10.43; -15.64; -10.65; -9.89; -4.17 | — |
| SECONDARY Panels B, C, & D: Change From Baseline in Bleeding Time (BT) at 5 Hours Postdose on Last Day After Multiple Doses of MK-3614 or Placebo |
1.21; 0.61; 1.23; 1.29 | — |
| SECONDARY Cyclic Guanosine Monophosphate (cGMP) Concentration Levels After Multiple Doses of MK-3614 |
443.55; 507.86; 517.34; 405.57; 269.72; 515.43 | — |
Summary
This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of MK-3614 in male participants with mild to moderate hypertension. The primary hypotheses are: 1) Multiple oral doses of MK-3614 are sufficiently safe and well tolerated to permit continued clinical investigation 2) Aortic Augmentation Index (Aix) is reduced 24 hours post the last dose of MK-3614 administered compared to placebo and 3) Increase in the 12-hour weighted averages (TWA 0-12hours) of the heart rate is within 15 beats per minute (bpm) of baseline on first day of multiple dosing of MK-3614 and within 10 bpm of baseline on last day of multiple dosing of MK-3614.
Eligibility Criteria
Inclusion Criteria
- Has mild to moderate hypertension
- Has grade 1 or 2 arterial hypertension being treated with a single antihypertensive drug
- Has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months; or who have discontinued smoking or the use of nicotine/nicotine-containing products for at least approximately 3 months
- Is in generally good health
Exclusion Criteria
- Has a history of clinically significant abnormalities or diseases
- Has a history of stroke, chronic seizures, or major neurological disorder
- Has a functional disability that can interfere with rising from a sitting position to the standing position
- Has any personal or family history of a bleeding or a clotting disorder
- Has a history of frequent nose bleeds or has recurrent or active gingivitis
- Has a history of cancer
- Has a history of clinically significant cardiac disease
- Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies approximately 2 weeks prior to the administration of study drug
- Consumes excessive amounts of alcohol
- Consumes excessive amounts of caffeinated beverages per day
- Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks of study
- Has a history of significant multiple and/or severe allergies (including latex) to prescription or non-prescription drugs or food
- Is currently a regular user of any illicit drugs or has a history of drug abuse within approximately 1 year
Data sourced from ClinicalTrials.gov (NCT01033643). 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.