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

NCT01130168 | Completed Phase 1 Results

• 2 other identifiers: 0000-1662010_537
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (10)

• 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

  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.

  Baseline (0 hrs), 12 hours post-dose (Day 1)

• Change From Baseline (0 Hours) to Week 4 in Heart-Rate-Corrected AIx After Multiple Doses of Treatment

  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.

  Baseline (0 hrs), 24 hours after the Day 28 dose

• TWA Change From Baseline (0 Hours) to 12 Hours in Central Systolic Blood Pressure (SBP) After A Single Dose of Treatment

  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.

  Baseline (0 hrs), 12 hours post-dose (Day 1)

• Change From Baseline (0 Hours) to Week 4 in Central SBP After Multiple Doses of Treatment

  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.

  Baseline (0 hrs), 24 hours after the Day 28 dose

• TWA Change From Baseline (0 Hours) to 12 Hours in Central Diastolic Blood Pressure (DBP) After A Single Dose of Treatment

  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.

  Baseline (0 hrs), 12 hours post-dose (Day 1)

• Change From Baseline (0 Hours) to Week 4 in Central DBP After Multiple Doses of Treatment

  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.

  Baseline (0 hrs), 24 hours after the Day 28 dose

• TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral SBP After A Single Dose of Treatment

  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.

  Baseline (0 hrs), 12 hours post-dose (Day 1)

• Change From Baseline (0 Hours) to Week 4 in Peripheral SBP After Multiple Doses of Treatment

  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.

  Baseline (0 hrs), 24 hours after the Day 28 dose

• TWA Change From Baseline (0 Hours) to 12 Hours in Peripheral DBP After A Single Dose of Treatment

  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.

  Baseline (0 hrs), 12 hours post-dose (Day 1)

• Change From Baseline (0 Hours) to Week 4 in Peripheral DBP After Multiple Doses of Treatment

  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.

  Baseline (0 hrs), 24 hours after the Day 28 dose

Study Arms (6)

Placebo/ISMN ER/Amlodipine (Sequence 1)

EXPERIMENTAL

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.

Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

ISMN ER/Amlodipine/Placebo (Sequence 2)

EXPERIMENTAL

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.

Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

Amlodipine/Placebo/ISMN ER (Sequence 3)

EXPERIMENTAL

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.

Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

ISMN ER/Placebo/Amlodipine (Sequence 4)

EXPERIMENTAL

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.

Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

Placebo/Amlodipine/ISMN ER (Sequence 5)

EXPERIMENTAL

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.

Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

Amlodipine/ISMN ER/Placebo (Sequence 6)

EXPERIMENTAL

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.

Drug: Placebo; Drug: Comparator: Amlodipine; Drug: Comparator: ISMN ER

Interventions

Placebo DRUG

Placebo, capsule taken orally once daily during 4 weeks of treatment

Amlodipine/ISMN ER/Placebo (Sequence 6); Amlodipine/Placebo/ISMN ER (Sequence 3); ISMN ER/Amlodipine/Placebo (Sequence 2); ISMN ER/Placebo/Amlodipine (Sequence 4); Placebo/Amlodipine/ISMN ER (Sequence 5); Placebo/ISMN ER/Amlodipine (Sequence 1)

Comparator: Amlodipine DRUG

Amlodipine 10 mg, taken orally as two 5 mg capsules, single daily dose for 4 weeks

Amlodipine/ISMN ER/Placebo (Sequence 6); Amlodipine/Placebo/ISMN ER (Sequence 3); ISMN ER/Amlodipine/Placebo (Sequence 2); ISMN ER/Placebo/Amlodipine (Sequence 4); Placebo/Amlodipine/ISMN ER (Sequence 5); Placebo/ISMN ER/Amlodipine (Sequence 1)

Comparator: ISMN ER DRUG

ISMN ER 30 mg capsule, taken orally as single daily dose for 4 weeks

Amlodipine/ISMN ER/Placebo (Sequence 6); Amlodipine/Placebo/ISMN ER (Sequence 3); ISMN ER/Amlodipine/Placebo (Sequence 2); ISMN ER/Placebo/Amlodipine (Sequence 4); Placebo/Amlodipine/ISMN ER (Sequence 5); Placebo/ISMN ER/Amlodipine (Sequence 1)

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: May 25, 2010
• Study Start: May 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: October 9, 2015
• Results First Posted: May 28, 2012

Record last verified: 2015-10