The Effects of Antihypertensive Agents on Central Blood Pressure in Healthy Participants and Participants With Hypertension (MK-0000-166) (COMPLETED)

Phase 1

Completed

Conditions: Hypertension

Interventions: Drug: Placebo

Registration Number: NCT01130168

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: This study will test the relationship between CBP (central blood pressure) and PBP (peripheral blood pressure) effects after single and multiple doses of Isosorbide mononitrate extended release (ISMN ER) or Amlodipine besylate in participants with hypertension.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Participant is a male or female between 30 and 65 years of age (inclusive) at the pre-study (screening)
Female participant of childbearing potential must have a negative pregnancy test
Participant has a brachial systolic blood pressure >130 mm Hg

and <180 mm Hg

Participant has a Body Mass Index (BMI) that is >20 kg/m^2 and <35 kg/m^2
Participant has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Exclusion Criteria

Female Participant is pregnant or lactating
Participant anticipates the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) other than acetaminophen
Participant is currently a user (including "recreational use") of any illicit drugs, has a history of drug or alcohol abuse within approximately 2 years, or has a positive prestudy urine drug screen
Participant has a condition for which there is a warning, contraindication, or precaution against the use of ISMN ER including: acute myocardial infarction or congestive heart failure, hypotension, volume depletion, and pregnancy
Participant has a history of significant drug allergy or any clinically significant adverse experience of a serious nature related to the administration of either a marketed or an investigational drug, including nitrates, nitrites, Amlodipine, and ISMN ER

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo/ISMN ER/Amlodipine (Sequence 1)	Placebo	Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
Amlodipine/Placebo/ISMN ER (Sequence 3)	Placebo	Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
ISMN ER/Placebo/Amlodipine (Sequence 4)	Placebo	Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 2, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 3, with a 2-week washout between each period.
Placebo/Amlodipine/ISMN ER (Sequence 5)	Placebo	Participants received a dose-matched Placebo capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
ISMN ER/Amlodipine/Placebo (Sequence 2)	Placebo	Participants received a ISMN ER 30 mg capsule orally for 4 weeks during Period 1, followed by Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule orally for 4 weeks during Period 3, with a 2-week washout between each period.
Amlodipine/ISMN ER/Placebo (Sequence 6)	Placebo	Participants received Amlodipine 10 mg (two 5 mg capsules) orally for 4 weeks during Period 1, followed by a ISMN ER 30 mg capsule orally for 4 weeks during Period 2, followed by a dose-matched Placebo capsule for 4 weeks during Period, with a 2-week washout between each period.

Primary Outcome Measures

Name	Time	Method
Time-weighted Average (TWA) Change From Baseline (0 Hours) to 12 Hours in Heart-Rate-Corrected Augmentation Index (AIx) After A Single Dose of Treatment	Baseline (0 hrs), 12 hours post-dose (Day 1)	The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Single dose effects on AIx were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment	Baseline (0 hrs), 24 hours after the Day 28 dose	The augmentation index (AIx) is a measure of systemic arterial stiffness, and is the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. This value was used for all AIx analyses.
TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment	Baseline (0 hrs), 12 hours post-dose (Day 1)	Central SBP was measured by the SphygmoCor® device. Single dose effects on central SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment	Baseline (0 hrs), 24 hours after the Day 28 dose	Central SBP was measured by the SphygmoCor® device. Central SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Change From Baseline (0 Hours) to Week 4 in Peripheral DBP After Multiple Doses of Treatment	Baseline (0 hrs), 24 hours after the Day 28 dose	Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Central Diastolic Blood Pressure (DBP) After A Single Dose of Treatment	Baseline (0 hrs), 12 hours post-dose (Day 1)	Central DBP was measured by the SphygmoCor® device. Single dose effects on central DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
Change From Baseline (0 Hours) to Week 4 in Peripheral SBP After Multiple Doses of Treatment	Baseline (0 hrs), 24 hours after the Day 28 dose	Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Peripheral SBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
Change From Baseline (0 Hours) to Week 4 in Central DBP After Multiple Doses of Treatment	Baseline (0 hrs), 24 hours after the Day 28 dose	Central DBP was measured by the SphygmoCor® device. Central DBP was measured at baseline and at 24 hours post dose on Day 28 (Week 4) and expressed as a change from baseline.
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral SBP After A Single Dose of Treatment	Baseline (0 hrs), 12 hours post-dose (Day 1)	Peripheral SBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral SBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.
TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral DBP After A Single Dose of Treatment	Baseline (0 hrs), 12 hours post-dose (Day 1)	Peripheral DBP was measured by Brachial Sphygmomanometer (standard cuff). Single dose effects on peripheral DBP were estimated as a time-weighted average change from baseline over the 12-hour post single dose observation period.