Trial Outcomes & Findings for An Active-Controlled Early Phase Study of MK-8189 in Adults With Schizophrenia (MK-8189-005) (NCT NCT03055338)

Last Updated: 2024-08-29

Results Overview

The LSM change from baseline at week 4 was assessed for PANSS total score. The PANSS assesses the severity of schizophrenia symptoms through a clinician-rated inventory of 30 items organized in 3 subscales: 1) positive subscale (7 items); 2) negative subscale (7 items); and 3) general psychopathology subscale (16 items). For each item, symptoms are scored from 1 (absent) to 7 (extreme) and sum to a total PANSS score (range: 30-210). Higher scores reflect more severe symptoms of schizophrenia. Further, reduced symptom severity over time is reflected by decreases in score.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

224 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2024-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	MK-8189 Participants receive MK-8189 (4 mg controlled release \[CR\] oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) once daily (QD) for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.	Risperidone Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.
Overall Study STARTED	90	45	89
Overall Study COMPLETED	72	34	77
Overall Study NOT COMPLETED	18	11	12

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-8189 Participants receive MK-8189 (4 mg controlled release \[CR\] oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) once daily (QD) for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.	Risperidone Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.
Overall Study Lost to Follow-up	9	2	3
Overall Study No Post-treatment Protocol Contact	0	1	0
Overall Study Physician Decision	0	0	2
Overall Study Withdrawal by Subject	9	8	7

Baseline Characteristics

Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline PANSS assessment; and 3) had ≥1 post-randomization observation for PANSS score subsequent to ≥1 dose of study treatment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-8189 n=90 Participants Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.	Risperidone n=45 Participants Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 Participants Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.	Total n=224 Participants Total of all reporting groups
Age, Continuous	38.4 Years STANDARD_DEVIATION 7.4 • n=90 Participants	37.3 Years STANDARD_DEVIATION 8.0 • n=45 Participants	35.6 Years STANDARD_DEVIATION 7.6 • n=89 Participants	37.1 Years STANDARD_DEVIATION 7.7 • n=224 Participants
Sex: Female, Male Female	23 Participants n=90 Participants	8 Participants n=45 Participants	17 Participants n=89 Participants	48 Participants n=224 Participants
Sex: Female, Male Male	67 Participants n=90 Participants	37 Participants n=45 Participants	72 Participants n=89 Participants	176 Participants n=224 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=90 Participants	0 Participants n=45 Participants	0 Participants n=89 Participants	2 Participants n=224 Participants
Race (NIH/OMB) Asian	2 Participants n=90 Participants	0 Participants n=45 Participants	2 Participants n=89 Participants	4 Participants n=224 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=90 Participants	0 Participants n=45 Participants	1 Participants n=89 Participants	1 Participants n=224 Participants
Race (NIH/OMB) Black or African American	65 Participants n=90 Participants	37 Participants n=45 Participants	65 Participants n=89 Participants	167 Participants n=224 Participants
Race (NIH/OMB) White	21 Participants n=90 Participants	8 Participants n=45 Participants	20 Participants n=89 Participants	49 Participants n=224 Participants
Race (NIH/OMB) More than one race	0 Participants n=90 Participants	0 Participants n=45 Participants	1 Participants n=89 Participants	1 Participants n=224 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=90 Participants	0 Participants n=45 Participants	0 Participants n=89 Participants	0 Participants n=224 Participants
Positive and Negative Syndrome Scale (PANSS) Total Score	95.1 Score on a Scale STANDARD_DEVIATION 10.4 • n=89 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline PANSS assessment; and 3) had ≥1 post-randomization observation for PANSS score subsequent to ≥1 dose of study treatment.	95.3 Score on a Scale STANDARD_DEVIATION 12.4 • n=40 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline PANSS assessment; and 3) had ≥1 post-randomization observation for PANSS score subsequent to ≥1 dose of study treatment.	96.2 Score on a Scale STANDARD_DEVIATION 9.6 • n=89 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline PANSS assessment; and 3) had ≥1 post-randomization observation for PANSS score subsequent to ≥1 dose of study treatment.	95.6 Score on a Scale STANDARD_DEVIATION 10.45 • n=218 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline PANSS assessment; and 3) had ≥1 post-randomization observation for PANSS score subsequent to ≥1 dose of study treatment.
Clinical Global Impression Severity of Illness (CGI-S) Score	4.9 Score on a Scale STANDARD_DEVIATION 0.6 • n=89 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline CGI-S assessment; and 3) had ≥1 post-randomization observation for CGI-S score subsequent to ≥1 dose of study treatment.	5.0 Score on a Scale STANDARD_DEVIATION 0.7 • n=40 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline CGI-S assessment; and 3) had ≥1 post-randomization observation for CGI-S score subsequent to ≥1 dose of study treatment.	5.0 Score on a Scale STANDARD_DEVIATION 0.4 • n=89 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline CGI-S assessment; and 3) had ≥1 post-randomization observation for CGI-S score subsequent to ≥1 dose of study treatment.	4.9 Score on a Scale STANDARD_DEVIATION 0.57 • n=218 Participants • Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline CGI-S assessment; and 3) had ≥1 post-randomization observation for CGI-S score subsequent to ≥1 dose of study treatment.
Duration of Illness <= 10 Years	31 Participants n=90 Participants	18 Participants n=45 Participants	32 Participants n=89 Participants	81 Participants n=224 Participants
Duration of Illness > 10 Years	59 Participants n=90 Participants	27 Participants n=45 Participants	57 Participants n=89 Participants	143 Participants n=224 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline PANSS assessment; and 3) had ≥1 post-randomization observation for PANSS score subsequent to ≥1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Risperidone n=40 Participants Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 Participants Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.	MK-8189 n=89 Participants Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.
Least Squares Mean (LSM) Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4	-17.2 Score on a Scale Interval -22.8 to -11.6	-10.0 Score on a Scale Interval -13.7 to -6.2	-14.6 Score on a Scale Interval -18.2 to -11.1

PRIMARY outcome

Timeframe: Up to 6 weeks

Population: Includes all randomized and treated participants.

The percentage of participants experiencing an AE was assessed. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Outcome measures

Outcome measures
Measure	Risperidone n=45 Participants Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 Participants Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.	MK-8189 n=90 Participants Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.
Percentage of Participants Experiencing an Adverse Event (AE)	77.8 Percentage of Participants	53.9 Percentage of Participants	71.1 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: Includes all randomized and treated participants.

The percentage of participants discontinuing study treatment due to an AE was assessed. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Outcome measures

Outcome measures
Measure	Risperidone n=45 Participants Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 Participants Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.	MK-8189 n=90 Participants Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.
Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event	8.9 Percentage of Participants	7.9 Percentage of Participants	6.7 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Includes all randomized participants who: 1) received ≥1 dose of study treatment; 2) had a baseline CGI-S assessment; and 3) had ≥1 post-randomization observation for CGI-S score subsequent to ≥1 dose of study treatment.

The LSM change from baseline at week 4 was assessed for CGI-S score. The CGI-S is a 7-point clinician-rated scale for assessing the global severity of the participant's illness. Possible CGI-S scores range from 1 (participant normal, not ill) to 7 (participant extremely ill). Further, a decrease in CGI-S score indicates reduced severity of the participant's illness.

Outcome measures

Outcome measures
Measure	Risperidone n=40 Participants Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 Participants Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.	MK-8189 n=89 Participants Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.
Least Squares Mean (LSM) Change From Baseline in the Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 4	-1.0 Score on a Scale Interval -1.4 to -0.7	-0.7 Score on a Scale Interval -0.9 to -0.4	-0.9 Score on a Scale Interval -1.1 to -0.6

Adverse Events

MK-8189

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

Risperidone

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-8189 n=90 participants at risk Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.	Risperidone n=45 participants at risk Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 participants at risk Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.
Infections and infestations Otitis externa	0.00% 0/90 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/45 • Up to 6 weeks The analysis population includes all randomized and treated participants.	1.1% 1/89 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/90 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 1/45 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/89 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Psychiatric disorders Psychotic disorder	0.00% 0/90 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/45 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 2/89 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Psychiatric disorders Schizophrenia	0.00% 0/90 • Up to 6 weeks The analysis population includes all randomized and treated participants.	4.4% 2/45 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/89 • Up to 6 weeks The analysis population includes all randomized and treated participants.

Other adverse events

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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-8189 n=90 participants at risk Participants receive MK-8189 (4 mg CR oral tablet\[s\]) in combination with placebo matching risperidone (oral capsule\[s\]) QD for 4 weeks. Over the initial 7 treatment days, MK-8189 is titrated from 4 mg to 12 mg as follows: 4 mg (1 tablet; Day 1); 8 mg (2 tablets; Day 4); and 12 mg (3 tablets; Day 7). Placebo matching risperidone is mock titrated as follows: 1 capsule (Day 1), 2 capsules (Day 4), and 3 capsules (Day 7). After Day 7, MK-8189 is maintained at 12 mg (3 tablets) in combination with placebo matching risperidone (3 capsules), QD for 3 weeks.	Risperidone n=45 participants at risk Participants receive risperidone (2 mg oral capsule\[s\]) in combination with placebo matching MK-8189 (oral tablet\[s\]), QD for 4 weeks. Over the initial 7 treatment days, risperidone is titrated from 2 mg to 6 mg as follows: 2 mg (1 capsule; Day 1); 4 mg (2 capsules; Day 4); and 6 mg (3 capsules; Day 7). Placebo matching MK-8189 is mock titrated as follows: 1 tablet (Day 1), 2 tablets (Day 4), and 3 tablets (Day 7). After Day 7, risperidone is maintained at 6 mg (3 capsules) in combination with placebo matching MK-8189 (3 tablets), QD for 3 weeks.	Placebo n=89 participants at risk Participants receive both placebo matching MK-8189 (oral tablet\[s\]) as well as placebo matching Risperidone (oral capsule\[s\]), QD for 4 weeks. Over the initial 7 treatment days, placebo matching both MK-8189 and risperidone are respectively mock titrated as follows: 1 tablet/1 capsule (Day 1); 2 tablets/2 capsules (Day 4); and 3 tablets/3 capsules (Day 7). After Day 7, placebo matching both MK-8189 and risperidone are respectively maintained at 3 tablets/3 capsules, QD for 3 weeks.
Gastrointestinal disorders Diarrhoea	7.8% 7/90 • Number of events 9 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/45 • Up to 6 weeks The analysis population includes all randomized and treated participants.	3.4% 3/89 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Gastrointestinal disorders Dyspepsia	5.6% 5/90 • Number of events 5 • Up to 6 weeks The analysis population includes all randomized and treated participants.	6.7% 3/45 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.	5.6% 5/89 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Gastrointestinal disorders Nausea	15.6% 14/90 • Number of events 15 • Up to 6 weeks The analysis population includes all randomized and treated participants.	8.9% 4/45 • Number of events 4 • Up to 6 weeks The analysis population includes all randomized and treated participants.	5.6% 5/89 • Number of events 5 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Gastrointestinal disorders Vomiting	7.8% 7/90 • Number of events 7 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 1/45 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.	1.1% 1/89 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.
General disorders Fatigue	2.2% 2/90 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.	6.7% 3/45 • Number of events 4 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 2/89 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Investigations Weight increased	2.2% 2/90 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.	17.8% 8/45 • Number of events 8 • Up to 6 weeks The analysis population includes all randomized and treated participants.	4.5% 4/89 • Number of events 4 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Metabolism and nutrition disorders Decreased appetite	6.7% 6/90 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 1/45 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 2/89 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Akathisia	17.8% 16/90 • Number of events 16 • Up to 6 weeks The analysis population includes all randomized and treated participants.	8.9% 4/45 • Number of events 4 • Up to 6 weeks The analysis population includes all randomized and treated participants.	3.4% 3/89 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Dizziness	3.3% 3/90 • Number of events 4 • Up to 6 weeks The analysis population includes all randomized and treated participants.	8.9% 4/45 • Number of events 4 • Up to 6 weeks The analysis population includes all randomized and treated participants.	1.1% 1/89 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Dystonia	8.9% 8/90 • Number of events 10 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/45 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/89 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Headache	15.6% 14/90 • Number of events 18 • Up to 6 weeks The analysis population includes all randomized and treated participants.	11.1% 5/45 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.	13.5% 12/89 • Number of events 17 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Lethargy	1.1% 1/90 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.	6.7% 3/45 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.	1.1% 1/89 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Sedation	7.8% 7/90 • Number of events 7 • Up to 6 weeks The analysis population includes all randomized and treated participants.	13.3% 6/45 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 2/89 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Nervous system disorders Somnolence	6.7% 6/90 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.	4.4% 2/45 • Number of events 2 • Up to 6 weeks The analysis population includes all randomized and treated participants.	3.4% 3/89 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Psychiatric disorders Agitation	1.1% 1/90 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.	6.7% 3/45 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.	3.4% 3/89 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Psychiatric disorders Anxiety	7.8% 7/90 • Number of events 7 • Up to 6 weeks The analysis population includes all randomized and treated participants.	2.2% 1/45 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.	3.4% 3/89 • Number of events 3 • Up to 6 weeks The analysis population includes all randomized and treated participants.
Psychiatric disorders Insomnia	6.7% 6/90 • Number of events 6 • Up to 6 weeks The analysis population includes all randomized and treated participants.	0.00% 0/45 • Up to 6 weeks The analysis population includes all randomized and treated participants.	1.1% 1/89 • Number of events 1 • Up to 6 weeks The analysis population includes all randomized and treated participants.