Trial Outcomes & Findings for Adjuvant Treatment With a Glycine Uptake Inhibitor in Participants With Negative Symptoms of Schizophrenia (P05695) (MK-8435-001) (NCT NCT00725075)
NCT ID: NCT00725075
Last Updated: 2018-10-16
Results Overview
SANS was a 25-item clinician-rated instrument for assessing the negative symptoms of schizophrenia. SANS 1-22 Composite Score consisted of the SANS 25 scale minus the last 3 questions (attention items). The remaining non-attention items (affective flattening, alogia, avolition-apathy, and anhedonia-asociality) comprised the SANS 1-22 Composite Score. For each item, symptom severity was rated on a 6-point scale, from 0=absent to 5=severe. The SANS 1-22 Composite Score had a total scoring range of 0 to 110. Higher scores indicated more impairment. The SANS 1-22 Composite Score was reported using data from the adjusted site rater. A negative change from baseline indicated an improvement in symptoms.
COMPLETED
PHASE2
215 participants
Baseline and Week 12
2018-10-16
Participant Flow
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received add-on therapy with MK-8435 (Org 25935). 215 participants were randomized and 214 participants were treated. There was no stratification for SGA treatment.
Participant milestones
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
72
|
73
|
70
|
|
Overall Study
Treated
|
71
|
73
|
70
|
|
Overall Study
COMPLETED
|
61
|
65
|
61
|
|
Overall Study
NOT COMPLETED
|
11
|
8
|
9
|
Reasons for withdrawal
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Overall Study
Use of Excluded Medication
|
0
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
5
|
4
|
|
Overall Study
Adverse Event
|
2
|
1
|
1
|
|
Overall Study
Worsening of Disease
|
2
|
1
|
2
|
|
Overall Study
Inclusion/Exclusion Criteria
|
1
|
0
|
1
|
|
Overall Study
Other
|
1
|
0
|
0
|
Baseline Characteristics
Adjuvant Treatment With a Glycine Uptake Inhibitor in Participants With Negative Symptoms of Schizophrenia (P05695) (MK-8435-001)
Baseline characteristics by cohort
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=72 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=73 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=70 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
Total
n=215 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
37.8 Years
STANDARD_DEVIATION 10.1 • n=93 Participants
|
38.8 Years
STANDARD_DEVIATION 11.0 • n=4 Participants
|
38.1 Years
STANDARD_DEVIATION 10.5 • n=27 Participants
|
38.3 Years
STANDARD_DEVIATION 10.5 • n=483 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=93 Participants
|
27 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
82 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
46 Participants
n=27 Participants
|
133 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
SANS was a 25-item clinician-rated instrument for assessing the negative symptoms of schizophrenia. SANS 1-22 Composite Score consisted of the SANS 25 scale minus the last 3 questions (attention items). The remaining non-attention items (affective flattening, alogia, avolition-apathy, and anhedonia-asociality) comprised the SANS 1-22 Composite Score. For each item, symptom severity was rated on a 6-point scale, from 0=absent to 5=severe. The SANS 1-22 Composite Score had a total scoring range of 0 to 110. Higher scores indicated more impairment. The SANS 1-22 Composite Score was reported using data from the adjusted site rater. A negative change from baseline indicated an improvement in symptoms.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12
|
-13.50 Score on a Scale
Standard Deviation 12.58
|
-10.91 Score on a Scale
Standard Deviation 11.85
|
-11.21 Score on a Scale
Standard Deviation 11.28
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
PANSS was a 30-item clinician-rated instrument used for assessing the positive, negative, and general psychopathology symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme, with a total scoring range of 30 to 210. Higher scores indicated more impairment. A negative change from baseline indicated an improvement in symptoms.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12
|
-11.84 Score on a Scale
Standard Deviation 10.34
|
-10.69 Score on a Scale
Standard Deviation 10.40
|
-9.73 Score on a Scale
Standard Deviation 11.23
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
CDSS was a 9-item clinician-rated instrument used to evaluate depression in participants who have schizophrenia. For each item, symptom severity was rated on a 4-point scale, from 0=absent to 3=severe, with a total scoring range of 0 to 27. Higher scores indicated more impairment. A negative change from baseline indicated an improvement in symptoms.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12
|
-0.95 Score on a Scale
Standard Deviation 1.88
|
-0.76 Score on a Scale
Standard Deviation 1.88
|
-0.56 Score on a Scale
Standard Deviation 2.67
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Perception of emotion was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery. The participant identified different emotional states (happy, sad, angry, and calm \[neutral\]) presented in pictures of faces by choosing the appropriate word for the emotion. The raw score was the sum of correct responses minus errors. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Perception of Emotions Score at Week 12
|
1.42 Score on a Scale
Standard Deviation 4.18
|
1.55 Score on a Scale
Standard Deviation 4.35
|
-0.80 Score on a Scale
Standard Deviation 5.91
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Non-verbal reasoning was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery. The participant solved 15 visual analogies composed of geometric 2x2, 3x3, or 4x4 puzzles by choosing the most appropriate geometric figure that solved the matrix. The raw score was the sum of correct responses minus errors. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Non-Verbal Reasoning Score at Week 12
|
0.65 Score on a Scale
Standard Deviation 4.30
|
0.66 Score on a Scale
Standard Deviation 3.95
|
0.78 Score on a Scale
Standard Deviation 4.68
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Verbal memory was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery. The participant remembered 15 words within a field of 15 distractors immediately and after a twenty minute delay. The raw score was the sum of correct responses. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Verbal Memory Score at Week 12
|
-0.76 Score on a Scale
Standard Deviation 7.61
|
0.41 Score on a Scale
Standard Deviation 7.85
|
-0.78 Score on a Scale
Standard Deviation 8.60
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Visual memory was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery. The participant remembered 15 geometric figures within a field of 15 distractors immediately and after a twenty minute delay. The raw score was the sum of correct responses. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Visual Memory Score at Week 12
|
-0.35 Sore on a Scale
Standard Deviation 4.98
|
-1.73 Sore on a Scale
Standard Deviation 6.20
|
-1.34 Sore on a Scale
Standard Deviation 6.59
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Speed of complex information processing was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery-Symbol-digit Coding Test. The participant linked numbers to digits. The test consisted of serial presentations of screens, each containing a bank of 8 symbols above and 8 empty boxes below. The participant typed the number that corresponded to the symbol highlighted. The raw score was the processing time in milliseconds. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Speed of Complex Information Processing Score at Week 12
|
5.62 Score on a Scale
Standard Deviation 8.53
|
5.73 Score on a Scale
Standard Deviation 13.21
|
5.17 Score on a Scale
Standard Deviation 12.94
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Working memory was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery-4-Part Continuous Performance Test. The participant was presented with targets and remembered target presentation sequencing in order to respond to the directions. Only Part 4 of the 4 Part Continuous Performance Test contributed towards the working memory score. The raw score was the sum of correct responses minus errors. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Working Memory Score at Week 12
|
0.96 Score on a Scale
Standard Deviation 4.62
|
0.37 Score on a Scale
Standard Deviation 4.75
|
0.82 Score on a Scale
Standard Deviation 6.72
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
Sustained attention was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery-4-Part Continuous Performance Test. The participant was asked to identify a target shape/color when presented with a battery of different geometric shapes/colors. Only Parts 2 to 4 of the 4 Part Continuous Performance Test contributed towards the sustained attention score. The raw score was the sum of correct responses minus errors. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Sustained Attention Score at Week 12
|
0.96 Score on a Scale
Standard Deviation 10.76
|
3.81 Score on a Scale
Standard Deviation 11.14
|
1.95 Score on a Scale
Standard Deviation 15.88
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received ≥1 dose of study therapy and completed at least 8 weeks of treatment.
Executive functioning was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery-Shifting Attention Test. The participant matched geometric shapes either by shape or color. The raw score was the sum of correct responses minus errors. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Executive Functioning Score at Week 12
|
10.16 Score on a Scale
Standard Deviation 19.55
|
9.33 Score on a Scale
Standard Deviation 20.09
|
12.57 Score on a Scale
Standard Deviation 23.26
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received ≥1 dose of study therapy and completed at least 8 weeks of treatment.
Composite memory was a composite of verbal memory and visual memory and was measured by computer using the CNS-Vital Signs Neurocognitive Test Battery. The raw score was the sum of correct responses. The standard scores were normalized from raw scores and presented an age-matched score relative to a normative comparison database. Higher scores were better.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=62 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=67 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=62 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Composite Memory Score at Week 12
|
-1.26 Score on a Scale
Standard Deviation 10.64
|
-1.32 Score on a Scale
Standard Deviation 11.61
|
-2.12 Score on a Scale
Standard Deviation 12.35
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: All randomized participants who received ≥1 dose of study therapy.
The abbreviated Extrapyramidal Symptoms Rating Scale (ESRS-A) was a sum of the severity rating of a 24-item instrument assessing four types of movement disorders: parkinsonism, dystonia, dyskinesia, and akathisia. Each item was rated on a 7-point scale, from 0=absent to 6=severe. Higher scores indicated more impairment. A negative change from baseline indicated an improvement.
Outcome measures
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=71 Participants
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=73 Participants
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=70 Participants
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12
|
-0.8 Score on a Scale
Standard Deviation 2.2
|
-0.3 Score on a Scale
Standard Deviation 1.2
|
-1.0 Score on a Scale
Standard Deviation 3.4
|
Adverse Events
MK-8435 (Org 25935) 8-16 mg Per Day
MK-8435 (Org 25935) 24-32 mg Per Day
Placebo
Serious adverse events
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=71 participants at risk
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=73 participants at risk
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=70 participants at risk
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Nervous system disorders
Dizziness
|
1.4%
1/71 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/73 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/70 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Injury, poisoning and procedural complications
Fall
|
1.4%
1/71 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/73 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/70 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Injury, poisoning and procedural complications
Foot fracture
|
1.4%
1/71 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/73 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/70 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/71 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/73 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/70 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/71 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/73 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/70 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/71 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/73 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/70 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
Other adverse events
| Measure |
MK-8435 (Org 25935) 8-16 mg Per Day
n=71 participants at risk
Participants were maintained on a stable dose of Second Generation Antipsychotic (SGA) and received 4-8 mg MK-8435 (Org 25935) twice a day (BID), in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
MK-8435 (Org 25935) 24-32 mg Per Day
n=73 participants at risk
Participants were maintained on a stable dose of SGA and received 12-16 mg MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. The dose of MK-8435 (Org 25935) was titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose remained stable after Day 42 for the remainder of the study.
|
Placebo
n=70 participants at risk
Participants were maintained on a stable dose of SGA and received matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days.
|
|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
2.8%
2/71 • Number of events 2 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
5.5%
4/73 • Number of events 7 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
4.3%
3/70 • Number of events 3 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
3/71 • Number of events 3 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
9.6%
7/73 • Number of events 7 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/70 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Investigations
Blood pressure increased
|
1.4%
1/71 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/73 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
5.7%
4/70 • Number of events 4 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Nervous system disorders
Dizziness
|
2.8%
2/71 • Number of events 2 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
9.6%
7/73 • Number of events 10 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
0.00%
0/70 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Nervous system disorders
Headache
|
4.2%
3/71 • Number of events 4 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
6.8%
5/73 • Number of events 6 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
10.0%
7/70 • Number of events 7 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Nervous system disorders
Somnolence
|
2.8%
2/71 • Number of events 2 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
5.5%
4/73 • Number of events 4 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
1.4%
1/70 • Number of events 1 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Psychiatric disorders
Anxiety
|
2.8%
2/71 • Number of events 3 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
5.5%
4/73 • Number of events 4 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
2.9%
2/70 • Number of events 2 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
|
Psychiatric disorders
Insomnia
|
8.5%
6/71 • Number of events 7 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
6.8%
5/73 • Number of events 9 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
8.6%
6/70 • Number of events 6 • From treatment Day1 through follow-up (up to 120 days)
AEs were reported for all randomized participants who received ≥1 dose of study therapy for both the treatment and follow-up periods.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee Any scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the sponsor at least six weeks ahead of estimated publication or presentation, for written consent. The sponsor shall have the right to make its consent of information conditional upon proper representation of the interpretation of both the sponsor and the investigator(s) in the discussion of the data in such communications.
- Publication restrictions are in place
Restriction type: OTHER