Trial Outcomes & Findings for A Study to Investigate the Safety and Tolerability of MK-0517 in Healthy Subjects (MK-0517-012) (NCT NCT00990821)

NCT ID: NCT00990821

Last Updated: 2015-08-19

Results Overview

AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The AUC(0-inf) bioequivalence was evaluated for single doses of 100 and 115 mg MK-0517 PS80, IV and that of an oral 125-mg capsule of aprepitant. Period I to IV populations are not included in the outcome analysis because those were formulation and dose-finding/dose confirmation arms.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 188 participants
• Primary outcome timeframe: Up to 72 Hours Post Dose
• Results posted on: 2015-08-19

Participant Flow

One Investigator in the United States. Primary therapy period: 31-Jan-2005 to 01-Dec-2005.

Participant milestones

Measure	Part I, Panel A 100 mg MK-0517 (non-polysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non-PS80) or placebo → 125 mg aprepitant	Part I, Panel B 100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant	Part I, Panel C 40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant	Part II 2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam	Part III, Panel 1, Treatment Sequence 1 125 mg aprepitant → 90 mg MK-0517 (PS80)	Part III, Panel 1, Treatment Sequence 2 40 mg MK-0517 (non-PS80) → 125 mg aprepitant	Part III, Panel 2 40 mg MK-0517 (non-PS80)	Part IV 40 mg MK-0517 (non-PS80 formulation)	Part V, Treatment Sequence 1 125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)	Part V, Treatment Sequence 2 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant	Part V, Treatment Sequence 3 115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)	Part V, Treatment Sequence 4 125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)	Part V, Treatment Sequence 5 100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)	Part V, Treatment Sequence 6 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant
Overall Study STARTED	14	16	14	8	17	17	12	14	12	14	12	14	12	12
Overall Study COMPLETED	14	14	14	8	14	14	11	14	12	13	9	9	10	11
Overall Study NOT COMPLETED	0	2	0	0	3	3	1	0	0	1	3	5	2	1

Reasons for withdrawal

Measure	Part I, Panel A 100 mg MK-0517 (non-polysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non-PS80) or placebo → 125 mg aprepitant	Part I, Panel B 100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant	Part I, Panel C 40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant	Part II 2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam	Part III, Panel 1, Treatment Sequence 1 125 mg aprepitant → 90 mg MK-0517 (PS80)	Part III, Panel 1, Treatment Sequence 2 40 mg MK-0517 (non-PS80) → 125 mg aprepitant	Part III, Panel 2 40 mg MK-0517 (non-PS80)	Part IV 40 mg MK-0517 (non-PS80 formulation)	Part V, Treatment Sequence 1 125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)	Part V, Treatment Sequence 2 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant	Part V, Treatment Sequence 3 115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)	Part V, Treatment Sequence 4 125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)	Part V, Treatment Sequence 5 100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)	Part V, Treatment Sequence 6 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant
Overall Study Withdrawal by Subject	0	2	0	0	3	3	1	0	0	1	3	5	2	1

Baseline Characteristics

A Study to Investigate the Safety and Tolerability of MK-0517 in Healthy Subjects (MK-0517-012)

Baseline characteristics by cohort

Measure	Part I, Panel A n=14 Participants 100 mg MK-0517 (non-polysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non-PS80) or placebo → 125 mg aprepitant	Part I, Panel B n=16 Participants 100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant	Part I, Panel C n=14 Participants 40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant	Part II n=8 Participants 2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam	Part III, Panel 1, Treatment Sequence 1 n=17 Participants 125 mg aprepitant → 90 mg MK-0517 (PS80)	Part III, Panel 1, Treatment Sequence 2 n=17 Participants 40 mg MK-0517 (non-PS80) → 125 mg aprepitant	Part III, Panel 2 n=12 Participants 40 mg MK-0517 (non-PS80)	Part IV n=14 Participants 40 mg MK-0517 (non-PS80 formulation)	Part V, Treatment Sequence 1 n=12 Participants 125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)	Part V, Treatment Sequence 2 n=14 Participants 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant	Part V, Treatment Sequence 3 n=12 Participants 115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)	Part V, Treatment Sequence 4 n=14 Participants 125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)	Part V, Treatment Sequence 5 n=12 Participants 100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)	Part V, Treatment Sequence 6 n=12 Participants 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant	Total n=188 Participants Total of all reporting groups
Age, Continuous	31.2 years n=5 Participants	35.2 years n=7 Participants	33.1 years n=5 Participants	36.9 years n=4 Participants	33.2 years n=21 Participants	33.2 years n=8 Participants	32.4 years n=8 Participants	29.4 years n=24 Participants	31.9 years n=42 Participants	33.5 years n=42 Participants	31.3 years n=42 Participants	29.1 years n=42 Participants	30.4 years n=36 Participants	36.5 years n=36 Participants	32.6 years n=24 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	5 Participants n=4 Participants	11 Participants n=21 Participants	10 Participants n=8 Participants	10 Participants n=8 Participants	10 Participants n=24 Participants	7 Participants n=42 Participants	11 Participants n=42 Participants	6 Participants n=42 Participants	6 Participants n=42 Participants	4 Participants n=36 Participants	6 Participants n=36 Participants	112 Participants n=24 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	7 Participants n=8 Participants	2 Participants n=8 Participants	4 Participants n=24 Participants	5 Participants n=42 Participants	3 Participants n=42 Participants	6 Participants n=42 Participants	8 Participants n=42 Participants	8 Participants n=36 Participants	6 Participants n=36 Participants	76 Participants n=24 Participants

PRIMARY outcome

Timeframe: Up to 72 Hours Post Dose

Population: All participants in Part V who had at least one period of AUC data were included in the evaluation of pharmacokinetics. Participants without sufficient concentration data for an AUC calculation included: 6 participants in the Aprepitant (125 mg) , 8 participants in the MK-0517 (100 mg) group, and 5 participants in the MK-0517 (115 mg) group.

AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The AUC(0-inf) bioequivalence was evaluated for single doses of 100 and 115 mg MK-0517 PS80, IV and that of an oral 125-mg capsule of aprepitant. Period I to IV populations are not included in the outcome analysis because those were formulation and dose-finding/dose confirmation arms.

Outcome measures

Measure	Aprepitant (125 mg) n=70 Participants A single oral dose with an Aprepitant capsule	MK-0517 (100 mg) n=68 Participants 100 mg of MK0517 (PS80 formulation) as an IV (intravenous) administered over 15 minutes	MK-0517 (115 mg) n=71 Participants 115 mg of MK0517 (PS80 formulation) as an IV (intravenous) administered over 15 minutes
Area Under the Plasma-Time Curve (AUC[0 to Infinity]) for Aprepitant and MK-0517 for Study Part V	29215 ng*hr/mL Standard Deviation 15731	24961 ng*hr/mL Standard Deviation 10477	31724 ng*hr/mL Standard Deviation 14287

Adverse Events

90 mg MK-0517 (PS80)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

100 mg MK-0517 (PS80)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

100 mg MK-0517 (PS80) + 2 mg Midazolam

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

115 mg MK-0517 (PS80)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

150 mg MK-0517 (PS80)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

40 mg MK-0517 (Non-PS80)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

100 mg MK-0517 (Non-PS80)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

150 mg MK-0517 (Non-PS80)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

40 mg Aprepitant

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

125 mg Aprepitant

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

2 mg Midazolam

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	90 mg MK-0517 (PS80) n=31 participants at risk MK-0517, PS80 formulation, administered with a single IV administration	100 mg MK-0517 (PS80) n=82 participants at risk MK-0517, PS80 formulation, administered with a single IV administration	100 mg MK-0517 (PS80) + 2 mg Midazolam n=8 participants at risk PS80 formulation, administered with a single IV administration and a single oral administration of midazolam	115 mg MK-0517 (PS80) n=66 participants at risk MK-0517, PS80 formulation, administered with a single IV administration	150 mg MK-0517 (PS80) n=12 participants at risk MK-0517, PS80 formulation, administered with a single IV administration	40 mg MK-0517 (Non-PS80) n=36 participants at risk MK-0517, non-PS80 formulation, administered with a single IV administration	100 mg MK-0517 (Non-PS80) n=12 participants at risk MK-0517, PS80 formulation, administered with a single IV administration	150 mg MK-0517 (Non-PS80) n=11 participants at risk MK-0517, PS80 formulation, administered with a single IV administration	Placebo n=11 participants at risk Placebo matching MK-0517 (PS80 or non-PS80)	40 mg Aprepitant n=14 participants at risk Aprepitant administered by a single oral capsule	125 mg Aprepitant n=133 participants at risk Aprepitant administered as a single oral capsule	2 mg Midazolam n=8 participants at risk Midazolam administered as a single oral solution
General disorders Swelling	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	2.8% 1/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	27.3% 3/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
General disorders Pain	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	5.6% 2/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	16.7% 2/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
General disorders Induration	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	12.5% 1/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 3/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	16.7% 2/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	18.2% 2/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
General disorders Tenderness	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	1.2% 1/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	50.0% 4/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 1/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	5.6% 2/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	16.7% 2/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	45.5% 5/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
General disorders Infusion Site Pain	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.5% 7/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	12.5% 1/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	7.6% 5/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	2.8% 1/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 1/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	9.1% 1/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	12.5% 1/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 3/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	16.7% 2/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	18.2% 2/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Nervous system disorders Headache	19.4% 6/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	3.0% 2/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	16.7% 2/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	27.3% 3/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	18.2% 2/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	3.8% 5/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	12.5% 1/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 1/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	9.1% 1/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Investigations Intraocular Pressure Test	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 1/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Gastrointestinal disorders Nausea	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 1/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	8.3% 1/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Nervous system disorders Dizziness	6.5% 2/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	1.2% 1/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	7.1% 1/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.75% 1/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Nervous system disorders Somnolence	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	62.5% 5/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	25.0% 2/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Eye disorders Eye Irritation	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	7.1% 1/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Infections and infestations Nasopharyngitis	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	7.1% 1/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.
Investigations Blood Pressure Increased	0.00% 0/31 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/82 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/66 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/36 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/12 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/11 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	7.1% 1/14 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/133 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.	0.00% 0/8 • Up to 30 days after the last dose of study drug All 188 study participants are included in the safety population: Adverse events are reported for the actual doses given in any part of the study. Individual participants may have received more than one drug or more than one dose of a drug.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER