Trial Outcomes & Findings for Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172-013) (NCT NCT01390428)

Last Updated: 2018-09-14

Results Overview

Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

50 participants

Primary outcome timeframe

Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Results posted on

2018-09-14

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1-Mild Hepatic Impairment (HI) Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Overall Study STARTED	8	8	9	9	8	8
Overall Study COMPLETED	8	8	8	9	7	8
Overall Study NOT COMPLETED	0	0	1	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1-Mild Hepatic Impairment (HI) Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Overall Study Elective Surgery	0	0	0	0	1	0
Overall Study Withdrawal by Subject	0	0	1	0	0	0

Baseline Characteristics

Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Grazoprevir (MK-5172-013)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=9 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=9 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Total n=50 Participants Total of all reporting groups
Age, Continuous	54.1 Years STANDARD_DEVIATION 4.1 • n=5 Participants	54.5 Years STANDARD_DEVIATION 5.8 • n=7 Participants	53.3 Years STANDARD_DEVIATION 6.7 • n=5 Participants	52.3 Years STANDARD_DEVIATION 6.8 • n=4 Participants	52.1 Years STANDARD_DEVIATION 8.4 • n=21 Participants	52.0 Years STANDARD_DEVIATION 9.9 • n=10 Participants	53.1 Years STANDARD_DEVIATION 6.9 • n=115 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=10 Participants	12 Participants n=115 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=10 Participants	38 Participants n=115 Participants

PRIMARY outcome

Timeframe: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

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

Outcome measures

Outcome measures
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=8 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=8 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir Day 1	1.71 uM*hr Interval 1.1 to 2.65	1.42 uM*hr Interval 0.912 to 2.2	1.61 uM*hr Interval 0.791 to 3.29	0.321 uM*hr Interval 0.157 to 0.655	1.17 uM*hr Interval 0.541 to 2.55	0.0592 uM*hr Interval 0.0273 to 0.129
Area Under the Concentration Time-curve From 0 to 24 Hours (AUC0-24) of Grazoprevir Day 10	6.20 uM*hr Interval 4.19 to 9.18	3.74 uM*hr Interval 2.53 to 5.54	4.21 uM*hr Interval 2.48 to 7.14	0.874 uM*hr Interval 0.515 to 1.48	3.00 uM*hr Interval 1.71 to 5.26	0.257 uM*hr Interval 0.146 to 0.451

PRIMARY outcome

Timeframe: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

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

Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Outcome measures

Outcome measures
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=8 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=8 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Maximum Concentration (Cmax) of Grazoprevir Day 1	0.257 uM Interval 0.121 to 0.545	0.305 uM Interval 0.144 to 0.646	0.433 uM Interval 0.184 to 1.07	0.0580 uM Interval 0.0242 to 0.139	0.238 uM Interval 0.107 to 0.531	0.0157 uM Interval 0.00705 to 0.035
Maximum Concentration (Cmax) of Grazoprevir Day 10	1.40 uM Interval 0.903 to 2.17	1.02 uM Interval 0.658 to 1.58	0.631 uM Interval 0.334 to 1.19	0.106 uM Interval 0.0559 to 0.199	0.396 uM Interval 0.203 to 0.774	0.0304 uM Interval 0.0156 to 0.0595

PRIMARY outcome

Timeframe: Days 1 and 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

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

Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Outcome measures

Outcome measures
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=8 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=8 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Time to Peak Concentration (Tmax) of Grazoprevir Day 1	3.50 hr. Interval 1.0 to 12.0	2.50 hr. Interval 1.0 to 4.0	2.00 hr. Interval 1.5 to 4.0	1.75 hr. Interval 1.0 to 4.0	1.75 hr. Interval 1.0 to 3.0	1.50 hr. Interval 1.0 to 4.0
Time to Peak Concentration (Tmax) of Grazoprevir Day 10	3.00 hr. Interval 2.0 to 4.0	3.01 hr. Interval 1.5 to 4.0	3.00 hr. Interval 1.5 to 8.0	2.00 hr. Interval 1.0 to 6.0	1.75 hr. Interval 0.5 to 4.0	1.00 hr. Interval 0.5 to 3.0

PRIMARY outcome

Timeframe: Day 1 at 24 hours postdose

Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants with Severe HI and Matched Healthy to Severe HI are absent because they had a different Measure Type and Method of Dispersion

Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Outcome measures

Outcome measures
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=8 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=8 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Mild HI and Moderate HI and Healthy Matched to Mild HI and Moderate HI	21.4 nM Interval 18.2 to 25.2	11.5 nM Interval 9.8 to 13.5	17.7 nM Interval 8.73 to 35.8	5.90 nM Interval 2.92 to 11.9	—	—

PRIMARY outcome

Timeframe: Day 1 at 24 hours postdose

Population: Participants who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Participants with Mild HI, Moderate HI and Healthy Matched to Mild HI or Moderate HI are absent because they had a different Measure Type and Method of Dispersion

Outcome measures

Outcome measures
Measure	Part 1-Mild HI Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 1 for Participants With Severe HI and Healthy Matched to Severe HI	—	—	—	—	15.6 nM Interval 2.89 to 60.2	1.86 nM Interval 0.0 to 3.32

PRIMARY outcome

Timeframe: Days 10 at 24 hours postdose

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

Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Outcome measures

Outcome measures
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=8 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=8 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Concentrations 24 Hours Post-dose (C24) of Grazoprevir on Day 10	32.6 nM Interval 24.8 to 42.8	17.0 nM Interval 12.9 to 22.3	48.9 nM Interval 27.2 to 87.9	13.6 nM Interval 7.6 to 24.5	55.0 nM Interval 31.9 to 94.8	5.89 nM Interval 3.42 to 10.2

PRIMARY outcome

Timeframe: Day 10 at the following timepoints: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

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

Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Day 10 in order to determine the plasma t1/2 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.

Outcome measures

Outcome measures
Measure	Part 1-Mild HI n=8 Participants Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 Participants Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=8 Participants Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=8 Participants Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 Participants Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 Participants Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Apparent Terminal Half-life (t1/2) of Grazoprevir	54.24 hr. Geometric Coefficient of Variation 22.32	35.85 hr. Geometric Coefficient of Variation 47.15	39.59 hr. Geometric Coefficient of Variation 23.76	39.80 hr. Geometric Coefficient of Variation 17.34	42.00 hr. Geometric Coefficient of Variation 26.55	31.02 hr. Geometric Coefficient of Variation 41.99

Adverse Events

Part 1-Mild HI

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 1-Healthy Matched to Mild HI

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 2-Moderate HI

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 2-Healthy Matched to Moderate HI

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 3-Severe HI

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 3-Healthy Matched to Severe HI

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1-Mild HI n=8 participants at risk Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 participants at risk Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=9 participants at risk Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=9 participants at risk Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 participants at risk Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 participants at risk Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)

Other adverse events

Other adverse events
Measure	Part 1-Mild HI n=8 participants at risk Participants with mild HI received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 1-Healthy Matched to Mild HI n=8 participants at risk Healthy participants received 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study.	Part 2-Moderate HI n=9 participants at risk Participants with moderate HI received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 2-Healthy Matched to Moderate HI n=9 participants at risk Healthy participants received 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study.	Part 3-Severe HI n=8 participants at risk Participants with severe HI received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.	Part 3-Healthy Matched to Severe HI n=8 participants at risk Healthy participants received 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Ear and labyrinth disorders Tinnitus	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Eye disorders Vision blurred	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Constipation	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Diarrhoea	25.0% 2/8 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Faeces hard	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Flatulence	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Nausea	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Toothache	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Gastrointestinal disorders Vomiting	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
General disorders Fatigue	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
General disorders Pain	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Infections and infestations Rash pustular	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Injury, poisoning and procedural complications Contusion	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Injury, poisoning and procedural complications Muscle strain	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Injury, poisoning and procedural complications Procedural pain	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Investigations Weight increased	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Metabolism and nutrition disorders Hypokalaemia	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Musculoskeletal and connective tissue disorders Back pain	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Musculoskeletal and connective tissue disorders Myalgia	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Musculoskeletal and connective tissue disorders Neck pain	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Nervous system disorders Dizziness	25.0% 2/8 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Nervous system disorders Headache	37.5% 3/8 • Number of events 3 • 14 days after last dose (up to Day 24)	25.0% 2/8 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)
Nervous system disorders Lethargy	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Nervous system disorders Neuropathy peripheral	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Nervous system disorders Presyncope	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Psychiatric disorders Abnormal dreams	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)
Psychiatric disorders Insomnia	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	11.1% 1/9 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Respiratory, thoracic and mediastinal disorders Dry throat	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/8 • 14 days after last dose (up to Day 24)	25.0% 2/8 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Respiratory, thoracic and mediastinal disorders Rhinalgia	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Mechanical urticaria	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Papule	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Psoriasis	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • 14 days after last dose (up to Day 24)	25.0% 2/8 • Number of events 2 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Vascular disorders Haematoma	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)
Vascular disorders Hot flush	0.00% 0/8 • 14 days after last dose (up to Day 24)	12.5% 1/8 • Number of events 1 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/9 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)	0.00% 0/8 • 14 days after last dose (up to Day 24)

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.
Publication restrictions are in place

Restriction type: OTHER