A Multiple Dose Titration Study of MK-8892 in Participants With Pulmonary Hypertension and Left Heart Disease (MK-8892-007)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02078557
• Date of registration: 03/03/2014
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: A Multiple Dose Titration Study of MK-8892 in Participants With Pulmonary Hypertension and Left Heart Disease (MK-8892-007)
• Scientific title: A Multiple Dose Titration Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892 in Patients With Pulmonary Hypertension and Left Heart Disease
• Date of first enrolment: May 9, 2014
• Target sample size: 4
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02078557
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Belgium, Moldova, Republic of, Romania

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme Corp.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Pulmonary hypertension (out of proportion, PHOOP) and heart failure with reduced left
ventricular ejection fraction (PHOOP/rEF)

- If female, cannot be pregnant or breastfeeding. Females of reproductive potential must
agree to agree to use (and/or have their partner use) two (2) acceptable methods of
birth control throughout the study and until 2 weeks after the last dose of study drug
is administered

- Body mass index (BMI) <=35 kg/m^2 and and <=18 kg/m^2

- Has World Health Organization (WHO) Group 2 pulmonary hypertension (PAH)

- Stable heart failure on optimal medical therapy with no hospitalizations for
congestion due to heart failure within the previous 3 months

Exclusion Criteria:

- Primary pulmonary arterial hypertension or veno-occlusive disease (WHO Group 1), or
pulmonary hypertension secondary to other causes (WHO Groups 3 -5) including but not
limited to autoimmune disease, connective tissue disease, and Eisenmenger syndrome

- Currently treatment with or anticipates use of nitrate, phosphodiesterase type 5
(PDE5) inhibitor, or medications known to induce or inhibit cytochrome P450 3A4
(CYP3A4) metabolism, and cannot be transitioned off of this therapy for >=7 days prior
to dosing and through completion of this study

- Symptoms of coronary artery disease requiring therapy with nitrates, within the past 3
months

- Severe aortic or mitral stenosis, or severe aortic, mitral, or tricuspid
insufficiency.

- Significant carotid artery disease

- Restrictive, infiltrative (e.g., amyloidosis) or hypertrophic cardiomyopathy

- Mentally or legally institutionalized or incapacitated, has significant emotional
problems at the time of pre study (screening) visit or expected during the conduct of
the study or has a history of a clinically significant psychiatric disorder over the
last 5 years. Subjects who have had situational depression may be enrolled in the
study at the discretion of the investigator.

- History of stroke, chronic seizures, or major neurological disorder

- History of clinically significant endocrine (not including diabetes mellitus),
gastrointestinal, hematological, hepatic (not including chronic Hepatitis C),
immunological (not including chronic human immunodeficiency virus [HIV]), respiratory,
or genitourinary abnormalities or diseases. Participants with a history of childhood
asthma may be enrolled in the study at the discretion of the investigator.
Participants with controlled hypertension are allowed to be enrolled.

- Unable to refrain from or anticipates the use of any medication, including
prescription and non-prescription drugs or herbal remedies (such as St. John's Wort
[hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to
administration of the dose of study drug, throughout the study (including washout
intervals between treatment periods), until the post study visit. There may be certain
medications that will be permitted.

- Consumes excessive amounts of alcohol, defined as greater than 5 glasses of alcoholic
beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125
mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day

- Major surgery or donated blood within 8 weeks prior to the pre study (screening) visit

- Participated in another investigational study within 4 weeks prior to the pre study
(screening) visit

- History of significant multiple and/or severe allergies (including latex allergy), or
has had an anaphylactic reaction or significant intolerability to prescription or
nonprescription drugs or food

- Uses illicit drugs or has a history of drug (including alcohol) abuse within the past
6 months



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Left Heart Disease

Pulmonary Hypertension

Intervention(s)

Drug: MK-8892

Primary Outcome(s)

Number of Participants Who Discontinued Study Drug Due to an Adverse Event [Time Frame: Up to 28 days]

Number of Participants Who Experienced an Adverse Event [Time Frame: Up to 42 days]

Percentage Change From Baseline in Pulmonary Vascular Resistance (PVR) [Time Frame: Baseline and Day 28]

Secondary ID(s)

MK-8892-007

2013-004639-55

8892-007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 31/10/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02078557