Schizophrenia
Conditions
Keywords
Negative symptoms, Glycine Uptake inhibitor, Add-on treatment, Second Generation Antipsychotic
Brief summary
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.
Detailed description
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.
Interventions
DRUGMK-8435 (Org 25935) 4-8 mg
Administered orally 2 times a day (BID) for a final concentration of 8-16 mg/day
DRUGPlacebo
Matching placebo for MK-8435 (Org 25935) administered orally BID
DRUGMK-8435 (Org 25935) 12-16 mg
Administered orally BID for a final concentration of 24-32 mg/day
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Is diagnosed with non-first episode schizophrenia meeting Diagnostic and Statistical Manual (Version IV) criteria * Is receiving stable treatment with one of the following SGA: aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone * Is in the non-acute phase of illness and clinically stable for 3 months prior to study start as demonstrated by: treatment with current SGA or at least 12 weeks prior to study start; no increase in the level of psychiatric care due to worsening symptoms for at least 12 weeks prior to study start; and no dose change of SGA or change in medication to treat the symptoms of schizophrenia for 4 weeks prior to study start * Has a score ≥4 on 3 or more of the following Positive and Negative Symptoms Scale (PANSS) negative subscale items at study start: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance * Has an overall PANSS negative subscale score \> 20
Exclusion criteria
* Has an overall PANSS positive subscale score ≥20 * Has a score ≥5 on 2 or more of the following PANSS positive subscale items at study start: delusions, hallucinatory behavior, excitement, grandiosity, or suspiciousness/persecution * Has a score ≥9 on the modified InterSePT Scale for Suicidal Thinking * Has a score ≥9 on the Calgary Depression Scale for Schizophrenia * Has a score ≥3 on the clinical global impression of Parkinsonism of the abbreviated Extrapyramidal Symptom Rating Scale * Has untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, cardiovascular, hematological, immunological or cerebrovascular disease, malignancy, or other chronic and/or degenerative process * Has a history of seizure disorder beyond childhood or is taking any anticonvulsants to prevent seizures * Has a diagnosis of mental retardation or organic brain syndrome * Has a clinically relevant visual disturbance, such as cataract, color blindness, macular degeneration, glaucoma, or retinal disease * Has a concurrent diagnosis of substance dependence other than nicotine or caffeine dependence in the past 6 months prior to study start * Has a positive result on the urine alcohol/drug screen for alcohol or illicit drugs * Is pregnant or breastfeeding * Is being treated with high doses of benzodiazepines (\>4 mg per day lorazepam or equivalent) * Has an imminent risk of self-harm or harm to others * Has been treated with clozapine in the past 6 months prior to study start * Has been treated with lithium, valproate, lamotrigine, pregabalin, gabapentin, or carbamazepine in the past 12 weeks prior to study start * Has started treatment or has had a dose change of an (additional) antipsychotic, antidepressant,hypnotic or anxiolytic in the past 4 weeks prior to study start * Has had no demonstrated benefit of antipsychotic treatment within the previous five years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12 | Baseline and 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. |
| Change From Baseline in Perception of Emotions Score at Week 12 | Baseline and 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. |
| Change From Baseline in Non-Verbal Reasoning Score at Week 12 | Baseline and 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. |
| Change From Baseline in Verbal Memory Score at Week 12 | Baseline and 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. |
| Change From Baseline in Visual Memory Score at Week 12 | Baseline and 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. |
| Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12 | Baseline and 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. |
| Change From Baseline in Working Memory Score at Week 12 | Baseline and 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. |
| Change From Baseline in Sustained Attention Score at Week 12 | Baseline and 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. |
| Change From Baseline in Executive Functioning Score at Week 12 | Baseline and 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. |
| Change From Baseline in Composite Memory Score at Week 12 | Baseline and 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. |
| Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12 | Baseline and 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. |
| Change From Baseline in Speed of Complex Information Processing Score at Week 12 | Baseline and 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. |
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 72 |
| 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. | 73 |
| 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. | 70 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Inclusion/Exclusion Criteria | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Use of Excluded Medication | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 5 | 4 |
| Overall Study | Worsening of Disease | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | MK-8435 (Org 25935) 8-16 mg Per Day | MK-8435 (Org 25935) 24-32 mg Per Day | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 37.8 Years STANDARD_DEVIATION 10.1 | 38.8 Years STANDARD_DEVIATION 11 | 38.1 Years STANDARD_DEVIATION 10.5 | 38.3 Years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 31 Participants | 27 Participants | 24 Participants | 82 Participants |
| Sex: Female, Male Male | 41 Participants | 46 Participants | 46 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 71 | 26 / 73 | 17 / 70 |
| serious Total, serious adverse events | 2 / 71 | 2 / 73 | 1 / 70 |
Outcome results
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | 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 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12 | -10.91 Score on a Scale | Standard Deviation 11.85 |
| Placebo | Change From Baseline in Modified Scale for the Assessment of Negative Symptoms (SANS 1-22 Composite Score) at Week 12 | -11.21 Score on a Scale | Standard Deviation 11.28 |
Comparison: Comparison of Mean Change in Baseline: Least Squared Estimates with Statistical Inference.p-value: 0.26795% CI: [-6.25, 1.74]ANCOVA
Comparison: Comparison of Mean Change in Baseline: Least Squared Estimates with Statistical Inference.p-value: 0.96695% CI: [-3.91, 3.74]ANCOVA
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received ≥1 dose of study therapy and completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Composite Memory Score at Week 12 | -1.26 Score on a Scale | Standard Deviation 10.64 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Composite Memory Score at Week 12 | -1.32 Score on a Scale | Standard Deviation 11.61 |
| Placebo | Change From Baseline in Composite Memory Score at Week 12 | -2.12 Score on a Scale | Standard Deviation 12.35 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received ≥1 dose of study therapy and completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Executive Functioning Score at Week 12 | 10.16 Score on a Scale | Standard Deviation 19.55 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Executive Functioning Score at Week 12 | 9.33 Score on a Scale | Standard Deviation 20.09 |
| Placebo | Change From Baseline in Executive Functioning Score at Week 12 | 12.57 Score on a Scale | Standard Deviation 23.26 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received ≥1 dose of study therapy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12 | -0.8 Score on a Scale | Standard Deviation 2.2 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12 | -0.3 Score on a Scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Extrapyramidal Symptoms Rating Scale Score at Week 12 | -1.0 Score on a Scale | Standard Deviation 3.4 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Non-Verbal Reasoning Score at Week 12 | 0.65 Score on a Scale | Standard Deviation 4.3 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Non-Verbal Reasoning Score at Week 12 | 0.66 Score on a Scale | Standard Deviation 3.95 |
| Placebo | Change From Baseline in Non-Verbal Reasoning Score at Week 12 | 0.78 Score on a Scale | Standard Deviation 4.68 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Perception of Emotions Score at Week 12 | 1.42 Score on a Scale | Standard Deviation 4.18 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Perception of Emotions Score at Week 12 | 1.55 Score on a Scale | Standard Deviation 4.35 |
| Placebo | Change From Baseline in Perception of Emotions Score at Week 12 | -0.80 Score on a Scale | Standard Deviation 5.91 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Speed of Complex Information Processing Score at Week 12 | 5.62 Score on a Scale | Standard Deviation 8.53 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Speed of Complex Information Processing Score at Week 12 | 5.73 Score on a Scale | Standard Deviation 13.21 |
| Placebo | Change From Baseline in Speed of Complex Information Processing Score at Week 12 | 5.17 Score on a Scale | Standard Deviation 12.94 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Sustained Attention Score at Week 12 | 0.96 Score on a Scale | Standard Deviation 10.76 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Sustained Attention Score at Week 12 | 3.81 Score on a Scale | Standard Deviation 11.14 |
| Placebo | Change From Baseline in Sustained Attention Score at Week 12 | 1.95 Score on a Scale | Standard Deviation 15.88 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12 | -0.95 Score on a Scale | Standard Deviation 1.88 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12 | -0.76 Score on a Scale | Standard Deviation 1.88 |
| Placebo | Change From Baseline in the Calgary Depression Scale for Schizophrenia (CDSS) at Week 12 | -0.56 Score on a Scale | Standard Deviation 2.67 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | 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 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12 | -10.69 Score on a Scale | Standard Deviation 10.4 |
| Placebo | Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Schizophrenia at Week 12 | -9.73 Score on a Scale | Standard Deviation 11.23 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Verbal Memory Score at Week 12 | -0.76 Score on a Scale | Standard Deviation 7.61 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Verbal Memory Score at Week 12 | 0.41 Score on a Scale | Standard Deviation 7.85 |
| Placebo | Change From Baseline in Verbal Memory Score at Week 12 | -0.78 Score on a Scale | Standard Deviation 8.6 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Visual Memory Score at Week 12 | -0.35 Sore on a Scale | Standard Deviation 4.98 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Visual Memory Score at Week 12 | -1.73 Sore on a Scale | Standard Deviation 6.2 |
| Placebo | Change From Baseline in Visual Memory Score at Week 12 | -1.34 Sore on a Scale | Standard Deviation 6.59 |
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.
Time frame: Baseline and Week 12
Population: All randomized participants who received either MK-8435 (Org 25935) or placebo and who completed at least 8 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8435 (Org 25935) 8-16 mg Per Day | Change From Baseline in Working Memory Score at Week 12 | 0.96 Score on a Scale | Standard Deviation 4.62 |
| MK-8435 (Org 25935) 24-32 mg Per Day | Change From Baseline in Working Memory Score at Week 12 | 0.37 Score on a Scale | Standard Deviation 4.75 |
| Placebo | Change From Baseline in Working Memory Score at Week 12 | 0.82 Score on a Scale | Standard Deviation 6.72 |