Trial Outcomes & Findings for A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED) (NCT NCT01104545)

Last Updated: 2019-08-08

Results Overview

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in hypertensive participants

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Results posted on

2019-08-08

Participant Flow

Three panels, each consisting of 8 participants (8 healthy young males in Panel A and Panel B; and 8 with mild-to-moderate hypertension in Panel C) were randomized to receive either MK-3614 or matching placebo in a 3:1 ratio, respectively, in up to 4 treatment periods in Panel A, Panel B and Panel C.

Each period of each panel (with exception of 0.25 mg fasted/fed periods) will be re-randomized to receive either study drug or placebo, i.e., a participant could be assigned to receive study drug in one period and placebo in another. The same participants will receive 0.25 mg MK-3614 in a fasted and fed state.

Participant milestones

Participant milestones
Measure	Panel A - Healthy Healthy participants received a single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Panel B - Healthy Healthy participants received a single oral dose of MK-3614 0.5 mg, 0.75 mg, 0.25 mg twice a day (b.i.d.), 0.25 mg three times a day (t.i.d), or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Panel C - Hypertensive Hypertensive participants received a single oral dose of MK-3614 0.75 mg, 0.5 mg, 0.75 mg, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods.
Overall Study STARTED	8	8	8
Overall Study COMPLETED	8	7	6
Overall Study NOT COMPLETED	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Panel A - Healthy Healthy participants received a single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Panel B - Healthy Healthy participants received a single oral dose of MK-3614 0.5 mg, 0.75 mg, 0.25 mg twice a day (b.i.d.), 0.25 mg three times a day (t.i.d), or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Panel C - Hypertensive Hypertensive participants received a single oral dose of MK-3614 0.75 mg, 0.5 mg, 0.75 mg, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods.
Overall Study Adverse Event	0	1	2

Baseline Characteristics

A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panel A - Healthy n=8 Participants Healthy participants received a single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Panel B - Healthy n=8 Participants Healthy participants received a single oral dose of MK-3614 0.5 mg, 0.75 mg, 0.25 mg twice a day (b.i.d.), 0.25 mg three times a day (t.i.d), or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Panel C - Hypertensive n=8 Participants Hypertensive participants received a single oral dose of MK-3614 0.75 mg, 0.5 mg, 0.75 mg, 0.75 mg or matching placebo. There was at least a 7-day washout between the 4 dosing periods.	Total n=24 Participants Total of all reporting groups
Age, Continuous	28.8 years STANDARD_DEVIATION 6.8 • n=5 Participants	33.4 years STANDARD_DEVIATION 7.0 • n=7 Participants	46.6 years STANDARD_DEVIATION 9.4 • n=5 Participants	36.3 years STANDARD_DEVIATION 10.8 • n=4 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
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants

PRIMARY outcome

Timeframe: up to 7 days for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

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, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. AEs are reported by the dose taken at the time of the event.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 Participants Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B n=5 Participants Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B n=7 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants	100.0 Percentage of Participants	100.0 Percentage of Participants	80.0 Percentage of Participants	33.3 Percentage of Participants	66.7 Percentage of Participants	66.7 Percentage of Participants	66.7 Percentage of Participants	20.0 Percentage of Participants	60.0 Percentage of Participants	57.1 Percentage of Participants

PRIMARY outcome

Timeframe: up to 7 days for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

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, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who were discontinued from the study due to an AE were summarized. AEs are reported by the dose taken at the time of the event.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 Participants Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B n=5 Participants Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B n=7 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	16.7 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

PRIMARY outcome

Timeframe: up to 7 days for each dose level

Population: All participants in in Panel C who received at least 1 dose of study drug and had available data for endpoint.

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, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. The percentage of participants that reported at least 1 AE was summarized. AEs are reported by the dose taken at the time of the event.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=7 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants	75.0 Percentage of Participants	60.0 Percentage of Participants	57.1 Percentage of Participants	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: up to 7 days for each dose level

Population: All participants in in Panel C who received at least 1 dose of study drug and had available data for endpoint.

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, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who were discontinued from the study due to an AE were summarized. AEs are reported by the dose taken at the time of the event.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=7 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants	12.5 Percentage of Participants	0.0 Percentage of Participants	14.3 Percentage of Participants	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and who complied 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 had available data for the endpoint.

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of MK-3614 in healthy participants.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=4 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=5 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 Participants Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants	83.8 nM•h Standard Deviation 53.1	412.0 nM•h Standard Deviation 96.4	83.8 nM•h Standard Deviation 9.46	223.0 nM•h Standard Deviation 83.1	173.0 nM•h Standard Deviation 82.0	168.0 nM•h Standard Deviation 27.7	NA nM•h Standard Deviation NA AUC0-inf not calculated for multiple dose arms	NA nM•h Standard Deviation NA AUC0-inf not calculated for multiple dose arms	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in healthy participants.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=5 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 Participants Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Maximum Concentration (Cmax) of MK-3614- Healthy Participants	4.9 nM Standard Deviation 1.68	29.8 nM Standard Deviation 5.20	3.6 nM Standard Deviation 1.09	17.0 nM Standard Deviation 4.48	11.5 nM Standard Deviation 4.22	13.4 nM Standard Deviation 2.24	5.1 nM Standard Deviation 0.55	7.1 nM Standard Deviation 1.50	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Tmax of MK-3614 in healthy participants.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=5 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 Participants Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Time to Cmax (Tmax) of MK-3614- Healthy Participants	4.0 hour (hr) Interval 4.0 to 12.0	4.0 hour (hr) Interval 2.0 to 6.0	6.0 hour (hr) Interval 6.0 to 6.0	4.0 hour (hr) Interval 4.0 to 6.0	4.0 hour (hr) Interval 4.0 to 8.0	4.0 hour (hr) Interval 2.0 to 6.0	4.0 hour (hr) Interval 4.0 to 4.0	16.0 hour (hr) Interval 16.0 to 18.0	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the t1/2 of MK-3614 in healthy participants.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=5 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 Participants Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants	9.2 hr Standard Deviation 4.5	10.1 hr Standard Deviation 2.3	13.1 hr Standard Deviation 1.2	9.1 hr Standard Deviation 3.0	9.7 hr Standard Deviation 3.6	9.5 hr Standard Deviation 2.1	11.7 hr Standard Deviation 4.1	14.7 hr Standard Deviation 6.0	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Population: All participants in in Panel C who received at least 1 dose of study drug and who complied 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 had available data for the endpoint. Data were summarized by dose taken and not by sequence.

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of MK-3614 in hypertensive participants

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants	253.0 nM•h Standard Deviation 52.0	134.0 nM•h Standard Deviation 39.5	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in hypertensive participants

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants	19.1 nM Standard Deviation 3.88	10.9 nM Standard Deviation 1.55	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Tmax of MK-3614 in hypertensive participants

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Time to Cmax (Tmax) of MK-3614- Hypertensive Participants	4.0 hr Interval 2.0 to 4.0	4.0 hr Interval 4.0 to 4.0	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the t1/2 of MK-3614 in hypertensive participants

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants	9.1 hr Standard Deviation 2.8	8.7 hr Standard Deviation 1.4	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline and 24 hours post-dose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Heart rate measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=12 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=13 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Change From Baseline in Heart Rate - Healthy Participants	-4.7 Beats per minute (bpm) Standard Deviation 3.7	-0.6 Beats per minute (bpm) Standard Deviation 7.2	5.4 Beats per minute (bpm) Standard Deviation 7.2	2.5 Beats per minute (bpm) Standard Deviation 4.8	-0.3 Beats per minute (bpm) Standard Deviation 5.9	6.3 Beats per minute (bpm) Standard Deviation 11.8	3.8 Beats per minute (bpm) Standard Deviation 6.6	—	—	—

PRIMARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Brachial arterial systolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=12 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=13 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants	-3.3 mmHg Standard Deviation 4.8	2.4 mmHg Standard Deviation 2.3	-2.6 mmHg Standard Deviation 5.3	-1.0 mmHg Standard Deviation 9.2	-3.1 mmHg Standard Deviation 5.7	-3.0 mmHg Standard Deviation 8.0	-0.2 mmHg Standard Deviation 7.4	—	—	—

PRIMARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Brachial arterial diastolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=12 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=13 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants	-1.7 mmHg Standard Deviation 3.1	0.8 mmHg Standard Deviation 6.7	-2.8 mmHg Standard Deviation 5.4	-1.0 mmHg Standard Deviation 5.6	-1.8 mmHg Standard Deviation 4.0	3.2 mmHg Standard Deviation 6.0	-0.6 mmHg Standard Deviation 3.3	—	—	—

PRIMARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

HR measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of sequence.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=7 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Change From Baseline in Heart Rate - Hypertensive Participants	0.7 bpm Standard Deviation 8.1	0.8 bpm Standard Deviation 10.7	-8.4 bpm Standard Deviation 8.5	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=7 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants	-5.2 mmHg Standard Deviation 14.2	-10.0 mmHg Standard Deviation 13.0	-18.1 mmHg Standard Deviation 15.6	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=7 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants	0.3 mmHg Standard Deviation 9.3	-4.4 mmHg Standard Deviation 6.5	-9.1 mmHg Standard Deviation 6.9	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Population: All participants in Panels A who received at least 1 dose of study drug and who complied 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 had available data for the endpoint.

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of 0.25 mg MK-3614 in healthy participant when administered after an 8 hour fast and after a high-fat breakfest.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=4 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed	83.8 nM•h Standard Deviation 53.1	83.8 nM•h Standard Deviation 9.46	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level

Population: All participants in Panel A who received at least 1 dose of study drug and who complied 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 had available data for the endpoint.

Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of 0.25 mg MK-3614 when administered after an 8 hour fast and after a high-fat breakfest.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed	4.85 nM Standard Deviation 1.68	3.56 nM Standard Deviation 1.09	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Augmentation index was measured at predose (baseline), and 1, 4, 8, 12, and 24 hours postdose by aplanation tonometry of radial artery. The change from baseline at 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=12 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=13 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants	-4.7 Percentage change Standard Deviation 10.1	-5.2 Percentage change Standard Deviation 7.9	-0.8 Percentage change Standard Deviation 3.1	-1.8 Percentage change Standard Deviation 6.0	-3.0 Percentage change Standard Deviation 4.0	-1.5 Percentage change Standard Deviation 6.0	0.8 Percentage change Standard Deviation 4.1	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.

Augmentation index was measured at predose (baseline), and 1, 4, 8, 12, and 24 hours postdose by aplanation tonometry of radial artery. The change from baseline at 24 hours postdose was summarized.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=8 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=7 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants	2.0 Percentage change Standard Deviation 6.4	-2.3 Percentage change Standard Deviation 4.9	1.1 Percentage change Standard Deviation 5.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Blood was to be drawn at predose (baseline) and 3 and 24 hours postdose and bleeding time was to be assessed using a Newborn Surgicutt device. Change in bleeding time from baseline at 24 hours postdose were to be summarized. Due to change in number of blood draws and total blood volume restrictions, bleeding time assessment was not performed as planned.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Blood was drawn at predose (baseline) and 1, 4, 8, and 24 hours postdose. The change in cyclic GMP at 24 hours postdose was summarized. Due to change in number of blood draws and total blood volume restrictions, data for GMP were only collected for first 2 periods of each panel. Therefore only limited data were available and summarized. Data for each specific dose were combined regardless of panel.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=5 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=12 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 Participants Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=11 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants	0.1 Percentage change Standard Deviation 0.1	0.0 Percentage change Standard Deviation 0.0	0.2 Percentage change Standard Deviation 0.1	—	0.0 Percentage change Standard Deviation 0.1	0.0 Percentage change Standard Deviation 0.0	0.0 Percentage change Standard Deviation 0.1	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=2 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants	—	0.2 Percentage change Standard Deviation 0.2	0.0 Percentage change Standard Deviation 0.2	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panels A and B who received at least 1 dose of study drug and had available data for endpoint.

Platelet aggregation induced by adenosine diphosphate (ADP) was measured at predose (baseline) and 3 and 24 hours postdose. Percent inhibition from baseline at 24 hours postdose was calculated. Due to change in number of blood draws and total blood volume restrictions, data for platelet aggregation were only collected for first 2 periods of each panel. Therefore only limited data were available and summarized. Data for each specific dose were combined regardless of panel.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=12 Participants Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=3 Participants Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants	—	—	—	—	-22.3 Percentage change Standard Deviation 26.3	—	-5.0 Percentage change Standard Deviation 12.8	—	—	—

SECONDARY outcome

Timeframe: Baseline and 24 hours postdose for each dose level

Population: All participants in Panel C who received at least 1 dose of study drug and had available data for endpoint.

Outcome measures

Outcome measures
Measure	0.25 mg MK-3614 Panel A Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 Participants Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=2 Participants Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants	—	-9.3 Percentage change Standard Deviation 12.9	-19.5 Percentage change Standard Deviation 21.9	—	—	—	—	—	—	—

Deaths: 0 deaths

Placebo Panel C

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	0.25 mg MK-3614 Panel A n=6 participants at risk Participants received a single oral dose of 0.25 mg MK-3614 after an 8-hour fast	1.25 mg MK-3614 Panel A n=6 participants at risk Participants received a single oral dose of 1.25 mg MK-3614 after an 8-hour fast	0.25 mg w/ Food MK-3614 Panel A n=5 participants at risk Participants received a single oral dose of 0.25 mg MK-3614 after ingesting a high-fat breakfest	0.75 mg MK-3614 Panel A n=6 participants at risk Participant received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	Placebo Panel A n=6 participants at risk Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel B n=6 participants at risk Participants received a single oral dose of 0.50 mg MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel B n=6 participants at risk Participants received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.25 mg b.i.d. MK-3614 Panel B n=5 participants at risk Participants received a single daily dose of 0.25 mg MK-3614 b.i.d.	0.25 mg t.i.d MK-3614 Panel B n=5 participants at risk Participants received a single daily oral dose of 0.25 mg MK-3614 t.i.d.	Placebo Panel B n=7 participants at risk Participants received a single oral dose of placebo for MK-3614 after an 8-hour fast	0.75 mg MK-3614 Panel C n=8 participants at risk Participant received a single oral dose of 0.75 mg MK-3614 after an 8-hour fast	0.5 mg MK-3614 Panel C n=5 participants at risk Participants received a single oral dose of 0.5 mg MK-3614 after an 8-hour fast	Placebo Panel C n=7 participants at risk Participant received a single oral dose of placebo for MK-3614 after an 8-hour fast
Cardiac disorders Atrioventricular block second degree	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Cardiac disorders Extrasystoles	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Cardiac disorders Palpitations	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Cardiac disorders Sinus tachycardia	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Cardiac disorders Supraventricular tachycardia	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Cardiac disorders Ventricular extrasystoles	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Gastrointestinal disorders Nausea	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Gastrointestinal disorders Toothache	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
General disorders Fatigue	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Infections and infestations Bronchitis	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Infections and infestations Gastroenteritis	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Infections and infestations Influenza	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Infections and infestations Nasopharyngitis	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	25.0% 2/8 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Infections and infestations Respiratory tract infection	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Infections and infestations Rhinitis	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Blood immunoglobulin E increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Blood pressure orthostatic decreased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Blood pressure systolic increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 24 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations C-reactive protein increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Electrocardiogram QT prolonged	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 21 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Heart rate increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	33.3% 2/6 • Number of events 4 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Orthostatic heart rate response increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations Red blood cell sedimentation rate increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 3 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Investigations White blood cells urine positive	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Nervous system disorders Dizziness	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Nervous system disorders Dysstasia	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Nervous system disorders Headache	50.0% 3/6 • Number of events 3 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	50.0% 3/6 • Number of events 3 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	33.3% 2/6 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	66.7% 4/6 • Number of events 4 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	28.6% 2/7 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	37.5% 3/8 • Number of events 6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	20.0% 1/5 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	28.6% 2/7 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Nervous system disorders Presyncope	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Nervous system disorders Syncope	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Nervous system disorders Vibratory sense increased	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	16.7% 1/6 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	33.3% 2/6 • Number of events 2 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/8 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	14.3% 1/7 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/6 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	12.5% 1/8 • Number of events 1 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/5 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.	0.00% 0/7 • Up to 7 days postdose for each dose level (up to 15 weeks total) All participants that received at least 1 dose of study drug and had data available for endpoint.

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 study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER