Trial Outcomes & Findings for Efficacy and Safety of MK-1942 When Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression (TRD) (MK-1942-006) (NCT NCT04663321)

Last Updated: 2024-09-19

Results Overview

The change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score is presented. MADRS includes 10 participant-rated items, each scored on a scale from 0 (normal, no symptom) to 6 (symptoms of maximum severity) \[total scores range from 0 (normal/no symptom) to 60 (severe depression). Higher scores correspond to greater symptom severity, whereas a negative change from baseline score indicates improvement.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

99 participants

Primary outcome timeframe

Baseline and Week 3

Results posted on

2024-09-19

Participant Flow

Participants were enrolled and randomized at 27 study sites in the US.

Participant milestones

Participant milestones
Measure	MK-1942 Daily Dose Group Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Overall Study STARTED	40	19	40
Overall Study COMPLETED	28	15	35
Overall Study NOT COMPLETED	12	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-1942 Daily Dose Group Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Overall Study Study terminated by Sponsor	2	1	2
Overall Study Withdrawal by Subject	10	3	2
Overall Study Not provided	0	0	1

Baseline Characteristics

Efficacy and Safety of MK-1942 When Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression (TRD) (MK-1942-006)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-1942 Daily Dose Group n=40 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=40 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Total n=99 Participants Total of all reporting groups
Age, Continuous	49.4 Years STANDARD_DEVIATION 12.3 • n=5 Participants	48.3 Years STANDARD_DEVIATION 12.6 • n=7 Participants	48.7 Years STANDARD_DEVIATION 13.3 • n=5 Participants	48.9 Years STANDARD_DEVIATION 12.6 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants	60 Participants n=4 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants	39 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants	87 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants	73 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 3

Population: All randomized participants who received ≥1 dose of study intervention, have ≥1 post-treatment and -randomization endpoint observation, and have baseline data available are included.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=30 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=16 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=37 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3	-8.1 Units on a scale Interval -11.5 to -4.6	-12.5 Units on a scale Interval -17.3 to -7.7	-11.4 Units on a scale Interval -14.6 to -8.1

PRIMARY outcome

Timeframe: Baseline and Week 1

Population: All randomized participants who received ≥1 dose of study intervention, have ≥1 post-treatment and -randomization endpoint observation, and have baseline data available are included.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=37 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=39 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Change From Baseline in MADRS Total Score to Week 1	-5.2 Units on a scale Interval -7.9 to -2.6	-6.3 Units on a scale Interval -10.0 to -2.6	-8.1 Units on a scale Interval -10.7 to -5.5

PRIMARY outcome

Timeframe: Up to approximately 6 Weeks

Population: All randomized participants who received ≥11 dose of study intervention are included.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=40 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=40 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Number of Participants Who Experienced An Adverse Event (AE)	29 Participants	13 Participants	27 Participants

PRIMARY outcome

Timeframe: Up to approximately 4 Weeks

Population: All randomized participants who received ≥11 dose of study intervention are included.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=40 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=40 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Number of Participants Who Discontinued Study Treatment Due to an AE	4 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Week 3

Population: All randomized participants who received ≥1 dose of study intervention, have ≥1 post-treatment and -randomization endpoint observation, and have baseline data available are included.

The HAM-D17 scale was used to evaluate the depressive symptoms experienced over the past week. The HAM-D17 is a 17-item participant-rated scale, with each item scored from 0 to 2 or 4 (depending on the question) reflective of severity (0 is absence of symptom and higher scores indicate greater symptom severity). The total score ranges from 0 (no apparent symptoms) to 52 (most severe symptoms). A negative change from baseline indicates symptom improvement, and vice versa.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=30 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=16 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=37 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Change From Baseline in the Hamilton Depression Rating Scale (HAM-D17) Total Score to Week 3	-5.5 Units on a scale Interval -7.7 to -3.3	-8.2 Units on a scale Interval -11.2 to -5.1	-7.5 Units on a scale Interval -9.6 to -5.5

SECONDARY outcome

Timeframe: Baseline and Week 1

Population: All randomized participants who received ≥1 dose of study intervention, have ≥1 post-treatment and -randomization endpoint observation, and have baseline data available are included.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=37 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=39 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Change From Baseline in the HAM-D17 Scale Total Score to Week 1	-4.1 Units on a scale Interval -5.9 to -2.3	-4.6 Units on a scale Interval -7.2 to -2.1	-5.8 Units on a scale Interval -7.6 to -4.0

SECONDARY outcome

Timeframe: Baseline and Week 3

Population: All randomized participants who received ≥1 dose of study intervention, have ≥1 post-treatment and -randomization endpoint observation, and have baseline data available are included.

The CGI-S is rated on a 7-point scale using a range of responses from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher score corresponds to greater symptom severity. A negative change score indicates improvement, and vice versa.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=30 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=16 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=37 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 3	-0.9 Units on a scale Interval -1.3 to -0.5	-1.3 Units on a scale Interval -1.9 to -0.7	-1.1 Units on a scale Interval -1.5 to -0.7

SECONDARY outcome

Timeframe: Baseline and Week 1

Population: All randomized participants who received ≥1 dose of study intervention, have ≥1 post-treatment and -randomization endpoint observation, and have baseline data available are included.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=37 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=39 Participants Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 1	-0.4 Units on a scale Interval -0.7 to -0.1	-0.7 Units on a scale Interval -1.1 to -0.3	-0.8 Units on a scale Interval -1.1 to -0.5

SECONDARY outcome

Timeframe: Day 15: 12 (Daily Dose) or 72 (Intermittent Dose) hours postdose

Population: A subset of MK-1942-treated participants who complied with the protocol sufficiently to ensure that generated data are likely to exhibit the effects of treatment are included.

The mean plasma concentration of MK-1942 10 mg given as a single or multiple dose regimen was determined.

Outcome measures

Outcome measures
Measure	MK-1942 Daily Dose Group n=29 Participants Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=17 Participants Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Mean Plasma Concentration of MK-1942 Plasma Concentration	130 nM Standard Deviation 69.3	9.43 nM Standard Deviation 9.13	—

Adverse Events

MK-1942 Daily Dose Group

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

MK-1942 Intermittent Dose Group

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-1942 Daily Dose Group n=40 participants at risk Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 participants at risk Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=40 participants at risk Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Nervous system disorders Loss of consciousness	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	0.00% 0/19 • Up to ~6 weeks All treated participants are included.	2.5% 1/40 • Up to ~6 weeks All treated participants are included.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-1942 Daily Dose Group n=40 participants at risk Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	MK-1942 Intermittent Dose Group n=19 participants at risk Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.	Placebo n=40 participants at risk Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
Eye disorders Vision blurred	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Gastrointestinal disorders Abdominal distension	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Gastrointestinal disorders Constipation	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	5.0% 2/40 • Up to ~6 weeks All treated participants are included.
Gastrointestinal disorders Diarrhoea	15.0% 6/40 • Up to ~6 weeks All treated participants are included.	10.5% 2/19 • Up to ~6 weeks All treated participants are included.	7.5% 3/40 • Up to ~6 weeks All treated participants are included.
Gastrointestinal disorders Dry mouth	2.5% 1/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Gastrointestinal disorders Nausea	17.5% 7/40 • Up to ~6 weeks All treated participants are included.	15.8% 3/19 • Up to ~6 weeks All treated participants are included.	15.0% 6/40 • Up to ~6 weeks All treated participants are included.
Gastrointestinal disorders Vomiting	5.0% 2/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	5.0% 2/40 • Up to ~6 weeks All treated participants are included.
General disorders Disease progression	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Infections and infestations Influenza	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Infections and infestations Nasopharyngitis	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Injury, poisoning and procedural complications Accidental overdose	7.5% 3/40 • Up to ~6 weeks All treated participants are included.	0.00% 0/19 • Up to ~6 weeks All treated participants are included.	12.5% 5/40 • Up to ~6 weeks All treated participants are included.
Injury, poisoning and procedural complications Corneal abrasion	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Investigations Alanine aminotransferase increased	5.0% 2/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	2.5% 1/40 • Up to ~6 weeks All treated participants are included.
Nervous system disorders Dizziness	25.0% 10/40 • Up to ~6 weeks All treated participants are included.	31.6% 6/19 • Up to ~6 weeks All treated participants are included.	7.5% 3/40 • Up to ~6 weeks All treated participants are included.
Nervous system disorders Essential tremor	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Nervous system disorders Headache	12.5% 5/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	17.5% 7/40 • Up to ~6 weeks All treated participants are included.
Nervous system disorders Somnolence	2.5% 1/40 • Up to ~6 weeks All treated participants are included.	0.00% 0/19 • Up to ~6 weeks All treated participants are included.	10.0% 4/40 • Up to ~6 weeks All treated participants are included.
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Psychiatric disorders Insomnia	7.5% 3/40 • Up to ~6 weeks All treated participants are included.	0.00% 0/19 • Up to ~6 weeks All treated participants are included.	2.5% 1/40 • Up to ~6 weeks All treated participants are included.
Psychiatric disorders Panic attack	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Psychiatric disorders Restlessness	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.
Vascular disorders Hypotension	0.00% 0/40 • Up to ~6 weeks All treated participants are included.	5.3% 1/19 • Up to ~6 weeks All treated participants are included.	0.00% 0/40 • Up to ~6 weeks All treated participants are included.