Safety and Tolerability of MK-5478 in Participants With Hypertension (5478-001)

NCT01025843 | Completed Phase 1 Results

• 2 other identifiers: 5478-0012009-016048-38
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a two part introductory clinical trial with MK-5478. Part I will evaluate the safety, tolerability and pharmacokinetics and pharmacodynamics of MK-5478 in young, healthy males. Part II will evaluate the safety, tolerability and pharmacodynamic effects of MK-5478 in participants with hypertension. The primary hypothesis is that single oral doses of MK-5478 are sufficiently safe and well tolerated.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (2)

• Number of Participants With One or More Adverse Events (AEs)

  An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's 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 is temporally associated with the use of the SPONSOR's product, is also an AE.

  Up to 14 days after administration of last dose of study drug (up to Day 52)

• Number of Participants Who Discontinued Treatment Due to an AE

  An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's 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 is temporally associated with the use of the SPONSOR's product, is also an AE.

  Up to 24 hours after administration of study drug

Secondary Outcomes (3)

• Area Under the Plasma Concentration Versus Time Curve (AUC 0-infinity) of MK-5478 and Candesartan

  Pre-dose and up to 48 hours postdose

• Change From Baseline in Aortic Augmentation Index (AIx) of MK-5478 and Candesartan

  Baseline and 1 to 3 hours postdose

• Maximum Plasma Concentration (Cmax) of MK-5478 and Candesartan

  Pre-dose and up to 48 hours postdose

Study Arms (10)

Pbo → 5 mg → Candesartan → 24 mg → 38 mg

EXPERIMENTAL

Placebo in Period 1; 5 mg MK-5478 in Period 2; Candesartan in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

1 mg → 5 mg → 12 mg → Candesartan → Pbo

EXPERIMENTAL

1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Candesartan in Period 4; and Placebo in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

1 mg → Candesartan → Pbo → 24 mg → 38 mg

EXPERIMENTAL

1 mg MK-5478 in Period 1; Candesartan in Period 2: Placebo in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

1 mg → 5 mg → 12 mg → Pbo → Candesartan

EXPERIMENTAL

1 mg MK-5478 in Period 1; 5 mg MK-5478 in Period 2; 12 mg MK-5478 in Period 3; Placebo in Period 4; and Candesartan in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

Pbo→ 8 mg→ 18 mg → 2 mg fed→Candesartan

EXPERIMENTAL

Placebo in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Candesartan in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

2 mg→Pbo → Candesartan → Pbo fed→38 mg

EXPERIMENTAL

2 mg MK-5478 in Period 1; Placebo in Period 2; Candesartan in Period 3; Placebo in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

2 mg→Candesartan→Pbo→Candesartan fed→38 mg

EXPERIMENTAL

2 mg MK-5478 in Period 1; Candesartan in Period 2; Placebo in Period 3; Candesartan in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

2 mg → 8 mg → 18 mg → 2 mg fed → Pbo

EXPERIMENTAL

2 mg MK-5478 in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and Placebo in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

Candesartan→8 mg→ 18 mg →2 mg fed→38 mg

EXPERIMENTAL

Candesartan in Period 1; 8 mg MK-5478 in Period 2; 18 mg MK-5478 in Period 3; 2 mg MK-5478 in Period 4 with a high fat meal; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

Candesartan→Pbo → 12 mg → 24 mg→38 mg

EXPERIMENTAL

Candesartan in Period 1; Placebo in Period 2; 12 mg MK-5478 in Period 3; 24 mg MK-5478 in Period 4; and 38 mg MK-5478 in Period 5. There was a minimum 7 days washout between periods.

Drug: MK-5478; Drug: Comparator: Candesartan cilexetil; Drug: Comparator: Pbo

Interventions

MK-5478 DRUG

In Part I: Single dose administration of MK-5478 oral capsules, total doses of 1, 2, 5, 8, 12, 18, 24 or 38 mg.

1 mg → 5 mg → 12 mg → Candesartan → Pbo; 1 mg → 5 mg → 12 mg → Pbo → Candesartan; 1 mg → Candesartan → Pbo → 24 mg → 38 mg; 2 mg → 8 mg → 18 mg → 2 mg fed → Pbo; 2 mg→Candesartan→Pbo→Candesartan fed→38 mg; 2 mg→Pbo → Candesartan → Pbo fed→38 mg; Candesartan→8 mg→ 18 mg →2 mg fed→38 mg; Candesartan→Pbo → 12 mg → 24 mg→38 mg; Pbo → 5 mg → Candesartan → 24 mg → 38 mg; Pbo→ 8 mg→ 18 mg → 2 mg fed→Candesartan

Comparator: Candesartan cilexetil DRUG

Single dose administration of candesartan, 32 mg oral tablet

Also known as: Atacand/Amias

1 mg → 5 mg → 12 mg → Candesartan → Pbo; 1 mg → 5 mg → 12 mg → Pbo → Candesartan; 1 mg → Candesartan → Pbo → 24 mg → 38 mg; 2 mg → 8 mg → 18 mg → 2 mg fed → Pbo; 2 mg→Candesartan→Pbo→Candesartan fed→38 mg; 2 mg→Pbo → Candesartan → Pbo fed→38 mg; Candesartan→8 mg→ 18 mg →2 mg fed→38 mg; Candesartan→Pbo → 12 mg → 24 mg→38 mg; Pbo → 5 mg → Candesartan → 24 mg → 38 mg; Pbo→ 8 mg→ 18 mg → 2 mg fed→Candesartan

Comparator: Pbo DRUG

Placebo

1 mg → 5 mg → 12 mg → Candesartan → Pbo; 1 mg → 5 mg → 12 mg → Pbo → Candesartan; 1 mg → Candesartan → Pbo → 24 mg → 38 mg; 2 mg → 8 mg → 18 mg → 2 mg fed → Pbo; 2 mg→Candesartan→Pbo→Candesartan fed→38 mg; 2 mg→Pbo → Candesartan → Pbo fed→38 mg; Candesartan→8 mg→ 18 mg →2 mg fed→38 mg; Candesartan→Pbo → 12 mg → 24 mg→38 mg; Pbo → 5 mg → Candesartan → 24 mg → 38 mg; Pbo→ 8 mg→ 18 mg → 2 mg fed→Candesartan

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part I:
• Is a male between 18 to 50 years of age
• Is in good health
• Is a non-smoker
• Part II:
• Is male of non-child bearing potential between 18 and 50 years of age
• Has hypertension (high blood pressure)

You may not qualify if:

• Part I and Part II:
• Has a history of stroke, seizures or major neurological disorder
• Has a history of cancer
• Has a history of any cardiovascular disease
• Is unable to refrain from the use of any prescription or non-prescription drugs
• Consumes excessive amounts of alcohol or caffeine
• Has had major surgery, donated blood or participated in another investigational study in the past 4 weeks

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Interventions

candesartan cilexetil

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 Director

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2009
• First Posted: December 4, 2009
• Study Start: December 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: September 21, 2018
• Results First Posted: February 26, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share