Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK8266 in Hypertensive Men (MK-8266-002) (NCT NCT01096160)

Last Updated: 2019-08-12

Results Overview

Assessment of the number of participants with at least one clinical or laboratory AE in those receiving multiple oral doses of MK-8266. An AE is defined as 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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

Up to 24 days

Results posted on

2019-08-12

Participant Flow

Participant milestones

Participant milestones
Measure	Panel A: MK-8266 BID (1 mg) MK-8266 BID 1 mg, administered as oral capsules (0.7 mg AM + 0.3 mg PM) for 10 days	Panel A: Placebo BID Matching placebo capsules, administered orally for 10 days	Panel B: MK-8266 BID (1.8 mg) MK-8266 BID 1.8 mg, administered as oral capsules (1 mg AM + 0.8 mg PM) for 10 days	Panel B: Placebo BID Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo TID Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo TID Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo TID Matching placebo capsules, administered orally TID for 10 days
Overall Study STARTED	6	2	6	2	6	2	6	2	6	2
Overall Study COMPLETED	6	2	5	2	5	2	4	2	4	1
Overall Study NOT COMPLETED	0	0	1	0	1	0	2	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Panel A: MK-8266 BID (1 mg) MK-8266 BID 1 mg, administered as oral capsules (0.7 mg AM + 0.3 mg PM) for 10 days	Panel A: Placebo BID Matching placebo capsules, administered orally for 10 days	Panel B: MK-8266 BID (1.8 mg) MK-8266 BID 1.8 mg, administered as oral capsules (1 mg AM + 0.8 mg PM) for 10 days	Panel B: Placebo BID Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo TID Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo TID Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo TID Matching placebo capsules, administered orally TID for 10 days
Overall Study Adverse Event	0	0	1	0	0	0	0	0	0	1
Overall Study Met stopping criteria per protocol	0	0	0	0	1	0	2	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panel A: MK-8266 BID, 1 mg n=6 Participants MK-8266 BID 1 mg, administered as oral capsules (0.7 mg AM + 0.3 mg PM) for 10 days, or as matching placebo	Panel A: Placebo BID n=2 Participants Matching placebo capsules, administered orally for 10 days	Panel B: MK-8266 BID, 1.8 mg n=6 Participants MK-8266 BID 1 mg, administered as oral capsules (1 mg AM + 0.8 mg PM) for 10 days	Panel B: Placebo BID n=2 Participants Matching placebo capsules, administered orally for 10 days	Panel C: MK-8266 TID, 1.8 mg n=6 Participants MK-8266 TID 1.8 mg, administered as oral capsules (0.6 mg q6hr) for 10 days	Panel C: Placebo TID n=2 Participants Matching placebo capsules, administered orally for 10 days	Panel D: MK-8266 TID, 2.4 mg n=6 Participants MK-8266 TID 2.4 mg, administered as oral capsules (0.8 mg q6hr) for 10 days	Panel D: Placebo TID n=2 Participants Matching placebo capsules, administered orally for 10 days	Panel E: MK-8266 TID, 2.4 mg n=6 Participants MK-8266 TID 2.4 mg, administered as oral capsules (0.8 mg q6hr) for 10 days	Panel E: Placebo TID n=2 Participants Matching placebo capsules, administered orally for 10 days	Total n=40 Participants Total of all reporting groups
Age, Continuous	49.2 years STANDARD_DEVIATION 1.5 • n=5 Participants	47.5 years STANDARD_DEVIATION 4.9 • n=7 Participants	45.5 years STANDARD_DEVIATION 7.8 • n=5 Participants	52.0 years STANDARD_DEVIATION 1.4 • n=4 Participants	46.5 years STANDARD_DEVIATION 3.4 • n=21 Participants	54.0 years STANDARD_DEVIATION 1.4 • n=10 Participants	46.2 years STANDARD_DEVIATION 5.5 • n=115 Participants	46.5 years STANDARD_DEVIATION 7.8 • n=24 Participants	47.2 years STANDARD_DEVIATION 5.2 • n=42 Participants	48.5 years STANDARD_DEVIATION 0.7 • n=42 Participants	47.6 years STANDARD_DEVIATION 4.9 • n=42 Participants
Sex: Female, Male Female	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	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants	2 Participants n=10 Participants	6 Participants n=115 Participants	2 Participants n=24 Participants	6 Participants n=42 Participants	2 Participants n=42 Participants	40 Participants n=42 Participants
Baseline HR	70 Beats per minute n=5 Participants • All participants who received at least one dose of the investigational drug	90 Beats per minute n=7 Participants • All participants who received at least one dose of the investigational drug	79 Beats per minute n=5 Participants • All participants who received at least one dose of the investigational drug	89 Beats per minute n=4 Participants • All participants who received at least one dose of the investigational drug	74 Beats per minute n=21 Participants • All participants who received at least one dose of the investigational drug	69 Beats per minute n=10 Participants • All participants who received at least one dose of the investigational drug	72 Beats per minute n=115 Participants • All participants who received at least one dose of the investigational drug	88 Beats per minute n=24 Participants • All participants who received at least one dose of the investigational drug	74 Beats per minute n=42 Participants • All participants who received at least one dose of the investigational drug	81 Beats per minute n=42 Participants • All participants who received at least one dose of the investigational drug	73 Beats per minute n=42 Participants • All participants who received at least one dose of the investigational drug

PRIMARY outcome

Timeframe: Up to 24 days

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

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=6 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=2 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) n=6 Participants MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo n=2 Participants Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) n=6 Participants MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo n=2 Participants Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) n=6 Participants MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo n=2 Participants Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) n=6 Participants MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo n=2 Participants Matching placebo capsules, administered orally TID for 10 days
Participants Receiving MK-8266 or Placebo Who Experienced At Least One Adverse Event (AE) During Treatment and Postdose Follow-up	5 Count of Participants	0 Count of Participants	5 Count of Participants	1 Count of Participants	3 Count of Participants	1 Count of Participants	4 Count of Participants	1 Count of Participants	5 Count of Participants	2 Count of Participants

PRIMARY outcome

Timeframe: Up to 10 days

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

Assessment of the number of participants receiving MK-8266 who discontinued therapy due to an AE over 10 days of treatment. An AE is defined as 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. The number of participants in any treatment group who discontinued therapy due to an AE was primarily assessed for Days 0-10.

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=6 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=2 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) n=6 Participants MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo n=2 Participants Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) n=6 Participants MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo n=2 Participants Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) n=6 Participants MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo n=2 Participants Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) n=6 Participants MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo n=2 Participants Matching placebo capsules, administered orally TID for 10 days
Participants Receiving MK-8266 or Placebo Who Discontinued Treatment Due to an AE	0 Count of Participants	0 Count of Participants	1 Count of Participants	0 Count of Participants	0 Count of Participants	0 Count of Participants	0 Count of Participants	0 Count of Participants	0 Count of Participants	1 Count of Participants

PRIMARY outcome

Timeframe: Baseline and Day 10

Population: All participants who received at least one dose of the investigational drug and had SBP assessments at Baseline and on Day 10

Assessment of the change from baseline in SBP, obtained using a validated, semi-automated oscillometric device. Evaluated for MK-8266 relative to placebo in participants, as measured by the time weighted average change over 24 hours postdose (TWA\^0-24hrs) on dosing Day 10. Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this analysis.

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=6 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=5 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) n=5 Participants MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo n=8 Participants Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) n=9 Participants MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo Matching placebo capsules, administered orally TID for 10 days
Change From Baseline in Systolic Blood Pressure (SBP) Following Multiple Oral Doses of MK-8266 or Placebo Baseline value	141.5 Millimeters of mercury (mmHg) Standard Deviation 8.96	132.6 Millimeters of mercury (mmHg) Standard Deviation 6.66	148.6 Millimeters of mercury (mmHg) Standard Deviation 23.77	134.5 Millimeters of mercury (mmHg) Standard Deviation 8.98	146.7 Millimeters of mercury (mmHg) Standard Deviation 12.07	—	—	—	—	—
Change From Baseline in Systolic Blood Pressure (SBP) Following Multiple Oral Doses of MK-8266 or Placebo Change from Baseline at Day 10	-5.09 Millimeters of mercury (mmHg) Standard Deviation 7.04	-2.18 Millimeters of mercury (mmHg) Standard Deviation 6.80	-4.78 Millimeters of mercury (mmHg) Standard Deviation 7.64	0.77 Millimeters of mercury (mmHg) Standard Deviation 6.62	-3.18 Millimeters of mercury (mmHg) Standard Deviation 7.72	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 10 (24 hours postdose)

Population: All participants who received at least one dose of the investigational drug and had HR assessments 24 hours postdose on Day 10.

Assessment of HR (beats/min) on Day 10 (24-hours postdose) with MK-8266 relative to placebo in participants, as measured by the time weighted average change over 24 hours postdose (TWA\^0-24hrs). Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this analysis. Baseline HR values are shown in the Baseline Characteristics section for Panels A, B, C, D, E.

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=6 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=5 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) n=5 Participants MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo n=8 Participants Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) n=9 Participants MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo Matching placebo capsules, administered orally TID for 10 days
Heart Rate (HR) on Day 10 Following Multiple Oral Doses of MK-8266 or Placebo	65.89 Beats per minute Standard Deviation 5.59	69.32 Beats per minute Standard Deviation 7.87	62.30 Beats per minute Standard Deviation 5.28	66.10 Beats per minute Standard Deviation 5.38	62.04 Beats per minute Standard Deviation 5.98	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 10

Population: All participants who received at least one dose of the investigational drug and had AIx assessment on Day 10

Assessment of the central, ascending aortic blood pressure augmentation index (AIx), based on measurement of central pulse pressure at selected time points on Day 10, as measured by applanation tonometry of the radial artery. This outcome measure assessed the time weighted average change over 24 hours postdose (TWA\^0-24hrs) on dosing Day 10. Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this assessment.

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=6 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=5 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) n=5 Participants MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo n=8 Participants Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) n=9 Participants MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo Matching placebo capsules, administered orally TID for 10 days
Aortic Augmentation Index (AIx) on Day 10 Following Multiple Oral Doses of MK-8266 or Placebo	8.81 mmHg Standard Deviation 4.86	7.45 mmHg Standard Deviation 2.59	13.50 mmHg Standard Deviation 8.95	11.89 mmHg Standard Deviation 7.00	18.68 mmHg Standard Deviation 6.68	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Day 10

Population: All participants who received at least one dose of the investigational drug and had cGMP assessments at Baseline and on Day 10

Assessment of whole blood samples for cGMP analysis, based on samples obtained predose as well as 4 and 24 hours postdose on Day 1 and Day 10, and predose only on Day 4. The change from baseline in cGMP was assessed at 24 hours postdose on Day 10. Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this assessment.

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=6 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=5 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) n=5 Participants MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo n=8 Participants Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) n=9 Participants MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo Matching placebo capsules, administered orally TID for 10 days
Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) Following Multiple Oral Doses of MK-8266 or Placebo Baseline value	1.61 nanomoles (nM) Standard Deviation 0.77	0.74 nanomoles (nM) Standard Deviation 0.50	1.69 nanomoles (nM) Standard Deviation 1.15	2.68 nanomoles (nM) Standard Deviation 1.29	0.54 nanomoles (nM) Standard Deviation 0.21	—	—	—	—	—
Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) Following Multiple Oral Doses of MK-8266 or Placebo Change from Baseline at Day 10	1.34 nanomoles (nM) Standard Deviation 2.74	1.74 nanomoles (nM) Standard Deviation 4.62	0.43 nanomoles (nM) Standard Deviation 0.66	0.81 nanomoles (nM) Standard Deviation 2.78	1.05 nanomoles (nM) Standard Deviation 1.16	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Day 10 (5 hours postdose)

Population: All participants who received at least one dose of the investigational drug and had assessment of ADP-induced platelet aggregation on Day 10

The percent inhibition of ADP-induced platelet aggregation from Baseline to 5 hours postdose on Day 10 was assessed and is summarized here. Platelet aggregation was initiated by addition of ADP (2.5 µM) to the participant's blood sample. Aggregation was followed for 5 minutes after addition of the agonist, and the maximum percent of light transmission (extent of aggregation) obtained during this period, as well as the instrument-calculated slope (rate of aggregation), were reported. Post treatment platelet aggregation is expressed as a percent of each participant's pretreatment level of aggregation. Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this summary. The data are very limited. On Day 10 only 8 participants received MK-8266 0.8 mg TID and 3 participants received placebo.

Outcome measures

Outcome measures
Measure	Panel A: MK-8266 BID (1 mg) n=8 Participants MK-8266 1 mg (0.7 mg AM + 0.3 mg PM), administered orally for 10 days	Panel A: Placebo n=3 Participants Matching placebo capsules, administered orally BID for 10 days	Panel B: MK-8266 BID (1.8 mg) MK-8266 1.8 mg (1 mg AM + 0.8 mg PM), administered orally for 10 days	Panel B: Placebo Matching placebo capsules, administered orally BID for 10 days	Panel C: MK-8266 TID (1.8 mg) MK-8266 0.6 mg TID, administered as oral capsules (1.8 mg) for 10 days	Panel C: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel D: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel D: Placebo Matching placebo capsules, administered orally TID for 10 days	Panel E: MK-8266 TID (2.4 mg) MK-8266 0.8 mg TID, administered as oral capsules (2.4 mg) for 10 days	Panel E: Placebo Matching placebo capsules, administered orally TID for 10 days
Percent Inhibition of Platelet Aggregation Induced by Adenosine Diphosphate (ADP) Following Multiple Oral Doses of MK-8266 or Placebo	-12.3 Percent inhibition Standard Deviation 29.81	-12.4 Percent inhibition Standard Deviation 18.89	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Day 10 (5 hours postdose)

Population: All participants who received at least one dose of the investigational drug and had assessment of collagen-induced platelet aggregation on Day 10

The percent inhibition of collagen-induced platelet aggregation from Baseline to 5 hours postdose on Day 10 was assessed and is summarized here. Platelet aggregation was initiated by addition of collagen (2 µg/mL) to the participant's blood sample. Aggregation was followed for 5 minutes after addition of the agonist, and the maximum percent of light transmission (extent of aggregation) obtained during this period, as well as the instrument-calculated slope (rate of aggregation), were reported. Post treatment platelet aggregation is expressed as a percent of each participant's pretreatment level of aggregation. Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this summary. The data are very limited. On Day 10, only 8 participants received MK-8266 0.8 mg TID and 3 participants received placebo.