Trial Outcomes & Findings for Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-005) (NCT NCT01926509)

Results Overview

Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose on Days 1 and 28 to determine the AUC0-24hr.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 28

Results posted on

2018-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	MK-8892 Panel A Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) Participants were administered placebo to MK-8892 once daily for 28 days.
Overall Study STARTED	6	6	5	6
Overall Study COMPLETED	5	6	5	6
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-8892 Panel A Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) Participants were administered placebo to MK-8892 once daily for 28 days.
Overall Study vital sign met discontinuation criteria	1	0	0	0

Baseline Characteristics

Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-005)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-8892 Panel A n=6 Participants Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B n=6 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C n=5 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) n=6 Participants Participants were administered placebo to MK-8892 once daily for 28 days.	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 28

Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model and have data available for endpoint.

Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose on Days 1 and 28 to determine the AUC0-24hr.

Outcome measures

Outcome measures
Measure	MK-8892 Panel A n=6 Participants Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B n=6 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C n=5 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) Participants were administered placebo to MK-8892 once daily for 28 days.
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 at Day 1 and Day 28 Day 1	0.143 μM*hr Interval 0.08 to 0.24	0.123 μM*hr Interval 0.017 to 0.23	0.192 μM*hr Interval 0.09 to 0.4	—
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 at Day 1 and Day 28 Day 28	0.863 μM*hr Interval 0.49 to 1.51	0.595 μM*hr Interval 0.32 to 1.11	1.61 μM*hr Interval 0.77 to 3.35	—

PRIMARY outcome

Timeframe: Up to 42 days

Population: All participants who received at least one dose of the investigational drug

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants that reported at least 1 AE was summarized.

Outcome measures

Outcome measures
Measure	MK-8892 Panel A n=6 Participants Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B n=6 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C n=5 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) n=6 Participants Participants were administered placebo to MK-8892 once daily for 28 days.
Number of Participants Who Experienced an Adverse Event (AE)	1 Participants	1 Participants	4 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: All participants who received at least one dose of the investigational drug

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants who had study drug discontinued due to an AE was summarized.

Outcome measures

Outcome measures
Measure	MK-8892 Panel A n=6 Participants Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B n=6 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C n=5 Participants Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) n=6 Participants Participants were administered placebo to MK-8892 once daily for 28 days.
Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

MK-8892 Panel A

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

MK-8892 Panel B

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

MK-8892 Panel C

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo (Panels A and B)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	MK-8892 Panel A n=6 participants at risk Participants were administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel B n=6 participants at risk Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).	MK-8892 Panel C n=5 participants at risk Participants were administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).	Placebo (Panels A and B) n=6 participants at risk Participants were administered placebo to MK-8892 once daily for 28 days.
Cardiac disorders TACHYCARDIA	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	20.0% 1/5 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
Gastrointestinal disorders VOMITING	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	20.0% 1/5 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
General disorders ASTHENIA	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	20.0% 1/5 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
Investigations PLATELET COUNT DECREASED	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	16.7% 1/6 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/5 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
Nervous system disorders DIZZINESS	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	20.0% 1/5 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
Nervous system disorders HEADACHE	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	60.0% 3/5 • Number of events 3 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	16.7% 1/6 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/5 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.
Vascular disorders HYPOTENSION	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	20.0% 1/5 • Number of events 1 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.	0.00% 0/6 • Up to 42 days All participant that received at least 1 dose of study drug. Adverse events were summarized by randomly assigned panel.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER