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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01025843

5478-001

2009-016048-38 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

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)

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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20 participants in 10 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

2 mg → 8 mg → 18 mg → 2 mg fed → Pbo

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

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

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil

Candesartan→Pbo → 12 mg → 24 mg→38 mg

Experimental group

Description:

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.

Treatment:

Drug: Comparator: Pbo

Drug: MK-5478

Drug: Comparator: Candesartan cilexetil