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| ID | Type | Description | Link |
|---|---|---|---|
| MK-8435-001 | Other Identifier | Merck Registration Number | |
| 172003 | Other Identifier | Organon Protocol Number | |
| P05695 | Other Identifier | Schering-Plough Protocol Number | |
| 2006-003080-31 | EudraCT Number |
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The purpose of this study is to determine whether MK-8435 (Org 25935) is more effective than placebo in improving negative symptoms in participants with schizophrenia who are concurrently treated with a stable dose of a second generation antipsychotic.
The primary features of schizophrenia are characterized by positive (irrational thoughts and/or behavior) and negative symptoms. Negative symptoms are the gross absence of normal behavior and emotions, and usually include a general lack of engagement, social withdrawal, and loss of goal-directed behavior.
Negative symptoms may strongly affect daytime activities and quality of life. The effects of currently available antipsychotics on negative symptoms are not satisfactory and leave much room for improvement. MK-8435 (Org 25935) is an investigational drug that may help to correct the above characteristics of schizophrenia by facilitating the messenger function of an amino acid in the brain, called glutamate. Preliminary data suggest that lowered glutamate levels in schizophrenia are associated with a failure to activate relevant areas in the forebrain and with prominent negative symptoms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg per day | Experimental | Participants will be maintained on a stable dose of Second Generation Antipsychotic (SGA) and receive 4-8 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) can be titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose must remain stable after Day 42 for the remainder of the study. |
|
| MK-8435 (Org 25935) 24-32 mg per day | Experimental | Participants will be maintained on a stable dose of SGA and receive 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) can be titrated upward or downward within the specified dose range, as needed, up to Day 42 of the study. The dose must remain stable after Day 42 for the remainder of the study. |
|
| Placebo | Placebo Comparator | Participants will be maintained on a stable dose of SGA and receive matching placebo for MK-8435 (Org 25935) BID, in the morning and the evening, as add-on treatment for up to 87 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8435 (Org 25935) 4-8 mg | Drug | Administered orally 2 times a day (BID) for a final concentration of 8-16 mg/day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12 | 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. | Baseline and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24525661 | Derived | Schoemaker JH, Jansen WT, Schipper J, Szegedi A. The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial. J Clin Psychopharmacol. 2014 Apr;34(2):190-8. doi: 10.1097/JCP.0000000000000073. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C520612 | N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)aminomethylcarboxylic acid |
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| Placebo | Drug | Matching placebo for MK-8435 (Org 25935) administered orally BID |
|
| MK-8435 (Org 25935) 12-16 mg | Drug | Administered orally BID for a final concentration of 24-32 mg/day |
|
| Baseline and Week 12 |
| Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Perception of Emotions Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Non-Verbal Reasoning Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Verbal Memory Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Visual Memory Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Speed of Complex Information Processing Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Working Memory Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Sustained Attention Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Executive Functioning Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Composite Memory Score at Week 12 | 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. | Baseline and Week 12 |
| Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12 | 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. | Baseline and Week 12 |
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Adverse Event |
|
| Worsening of Disease |
|
| Inclusion/Exclusion Criteria |
|
| Other |
|
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| 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. |
| OG001 | 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. |
| OG002 | 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. |
|
|
|
| Secondary | Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Perception of Emotions Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Non-Verbal Reasoning Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Verbal Memory Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Visual Memory Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Sore on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Speed of Complex Information Processing Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Working Memory Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Sustained Attention Score at Week 12 | 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. | All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Executive Functioning Score at Week 12 | 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. | All randomized participants who received ≥1 dose of study therapy and completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Composite Memory Score at Week 12 | 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. | All randomized participants who received ≥1 dose of study therapy and completed at least 8 weeks of treatment. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| Secondary | Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12 | 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. | All randomized participants who received ≥1 dose of study therapy. | Posted | Mean | Standard Deviation | Score on a Scale | Baseline and Week 12 |
|
|
|
| 2 |
| 71 |
| 15 |
| 71 |
| EG001 | 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. | 2 | 73 | 26 | 73 |
| EG002 | 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. | 1 | 70 | 17 | 70 |
| Fall | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Psychotic disorder | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
| Schizophrenia | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
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.