Trial Outcomes & Findings for Treatment Study for Cognitive Deficits in Schizophrenia (NCT NCT00505076)

Results Overview

The primary outcome measure is the composite score on the Matrics Consensus Cognitive Battery (MCCB). The MCCB composite score is a standardized mean of the seven domain scores. T-scores are standardized to normative data, and have an estimated mean of 50 and SD of 10 in the general healthy population. Data reduction for analysis of neurocognitive testing used the following steps: i) individual neurocognitive test scores at baseline and follow-up were converted to t-scores; ii) t-scores within the pre-specified cognitive domains measured by more than one test were averaged to obtain a domain-specific t-score; and iii) domain-specific t-scores were averaged to create the MCCB composite score.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

4 weeks

Results posted on

2014-10-31

Participant Flow

Patients were recruited between June 2007 and July 2009.

46 subjects were excluded during screening.

Participant milestones

Participant milestones
Measure	MK-0777 8 mg BID Subjects treated with MK-0777 GEM, 8 mg BID(twice daily)	MK-0777 3 mg BID Subjects treated with MK-0777 GEM, 3 mg BID (twice daily)	Placebo BID Subjects treated with 2 tablets placebo BID (twice daily)
Overall Study STARTED	22	19	22
Overall Study COMPLETED	19	17	17
Overall Study NOT COMPLETED	3	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-0777 8 mg BID Subjects treated with MK-0777 GEM, 8 mg BID(twice daily)	MK-0777 3 mg BID Subjects treated with MK-0777 GEM, 3 mg BID (twice daily)	Placebo BID Subjects treated with 2 tablets placebo BID (twice daily)
Overall Study Adverse Event	1	0	1
Overall Study Protocol Violation	2	1	2
Overall Study Withdrawal by Subject	0	1	2

Baseline Characteristics

Treatment Study for Cognitive Deficits in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-077 8 mg BID n=22 Participants Subjects treated with MK-0777 GEM, 8 mg BID(twice daily)	MK-0777 3 mg BID n=19 Participants Subjects treated with MK-0777 GEM, 3 mg BID (twice daily)	Placebo BID n=22 Participants Subjects treated with 2 tablets placebo BID (twice daily)	Total n=63 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	19 Participants n=7 Participants	22 Participants n=5 Participants	63 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	44.9 years STANDARD_DEVIATION 8.7 • n=5 Participants	43.3 years STANDARD_DEVIATION 9.3 • n=7 Participants	40.0 years STANDARD_DEVIATION 10.9 • n=5 Participants	42.7 years STANDARD_DEVIATION 9.8 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	23 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants	40 Participants n=4 Participants
Region of Enrollment United States	22 participants n=5 Participants	19 participants n=7 Participants	22 participants n=5 Participants	63 participants n=4 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Fifty-three participants completed the study: MK-0777 3mg BID: 18; MK-0777 8mg BID: 18; placebo: 17. Three participants dropped out prior to receiving study drug (one randomized to each group) and 1 participant dropped out prior to any post-randomization ratings (randomized to placebo). These participants were not included in analyses.

The primary outcome measure is the composite score on the Matrics Consensus Cognitive Battery (MCCB). The MCCB composite score is a standardized mean of the seven domain scores. T-scores are standardized to normative data, and have an estimated mean of 50 and SD of 10 in the general healthy population. Data reduction for analysis of neurocognitive testing used the following steps: i) individual neurocognitive test scores at baseline and follow-up were converted to t-scores; ii) t-scores within the pre-specified cognitive domains measured by more than one test were averaged to obtain a domain-specific t-score; and iii) domain-specific t-scores were averaged to create the MCCB composite score.

Outcome measures

Outcome measures
Measure	MK-077 8 mg BID n=18 Participants Subjects treated with MK-0777, 8 mg BID	MK-0777 3 mg BID n=18 Participants Subjects treated with MK-0777 , 3 mg BID	Placebo BID n=17 Participants Subjects treated with placebo tablet BID
Composite MATRICS Consensus Cognitive Battery Score	27.9 composite score Standard Deviation 12.7	31.3 composite score Standard Deviation 13.9	32.5 composite score Standard Deviation 14.0

SECONDARY outcome

Timeframe: Baseline and end of treatment, a total of four weeks.

Population: Fifty-three participants completed the study: MK-0777 3mg BID: 18; MK-0777 8mg BID: 18; placebo: 17. Three participants dropped out prior to receiving study drug (one randomized to each group) and 1 participant dropped out prior to any post-randomization ratings (randomized to placebo). These participants were not included in analyses.

The UCSD Performance-Based Skills Assessment assessed functional capacity. The UPSA Summary Score has a range from 0 to 120. A higher score indicates less impairment.

Outcome measures

Outcome measures
Measure	MK-077 8 mg BID n=18 Participants Subjects treated with MK-0777, 8 mg BID	MK-0777 3 mg BID n=18 Participants Subjects treated with MK-0777 , 3 mg BID	Placebo BID n=17 Participants Subjects treated with placebo tablet BID
UPSA(UCSD Performance-Based Skills Assessment) Summary Score Baseline	91.7 UPSA Summary Score Standard Deviation 13.4	85.0 UPSA Summary Score Standard Deviation 18.8	95.0 UPSA Summary Score Standard Deviation 16.3
UPSA(UCSD Performance-Based Skills Assessment) Summary Score End of Treatment	90.4 UPSA Summary Score Standard Deviation 12.8	86.3 UPSA Summary Score Standard Deviation 18.7	96.5 UPSA Summary Score Standard Deviation 15.5

SECONDARY outcome

Timeframe: 4 Weeks (Baseline to End of Treatment)

Population: Fifty-three participants completed the study: MK-0777 3mg BID: 18; MK-0777 8mg BID: 18; placebo: 17. Three participants dropped out prior to receiving study drug (one randomized to each group) and 1 participant dropped out prior to any post-randomization ratings (randomized to placebo). These participants were not included in analyses.

The Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. The SCoRS Interviewer Global Rating of function has a range 1 to 10. Higher ratings indicate greater impairment.

Outcome measures

Outcome measures
Measure	MK-077 8 mg BID n=18 Participants Subjects treated with MK-0777, 8 mg BID	MK-0777 3 mg BID n=18 Participants Subjects treated with MK-0777 , 3 mg BID	Placebo BID n=17 Participants Subjects treated with placebo tablet BID
Schizophrenia Cognition Rating Scale (SCoRS) Score Baseline	4.1 SCoRS Score Standard Deviation 2.3	4.8 SCoRS Score Standard Deviation 2.3	3.8 SCoRS Score Standard Deviation 2.3
Schizophrenia Cognition Rating Scale (SCoRS) Score End of Treatment	4.0 SCoRS Score Standard Deviation 2.4	4.6 SCoRS Score Standard Deviation 2.1	3.6 SCoRS Score Standard Deviation 1.8

Adverse Events

MK-077 8 mg BID

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

MK-0777 3 mg BID

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-077 8 mg BID n=21 participants at risk Subjects treated with MK-0777 GEM, 8 mg BID(twice daily)	MK-0777 3 mg BID n=18 participants at risk Subjects treated with MK-0777 GEM, 3 mg BID (twice daily)	Placebo BID n=21 participants at risk Subjects treated with 2 tablets placebo BID (twice daily)
Infections and infestations Medical Hospitalization	0.00% 0/21 • 1 year	5.6% 1/18 • Number of events 1 • 1 year	0.00% 0/21 • 1 year
Nervous system disorders Psychosis Hospitalization	4.8% 1/21 • Number of events 1 • 1 year	0.00% 0/18 • 1 year	0.00% 0/21 • 1 year

Other adverse events

Other adverse events
Measure	MK-077 8 mg BID n=21 participants at risk Subjects treated with MK-0777 GEM, 8 mg BID(twice daily)	MK-0777 3 mg BID n=18 participants at risk Subjects treated with MK-0777 GEM, 3 mg BID (twice daily)	Placebo BID n=21 participants at risk Subjects treated with 2 tablets placebo BID (twice daily)
General disorders Sedation	9.5% 2/21 • Number of events 2 • 1 year	5.6% 1/18 • Number of events 1 • 1 year	4.8% 1/21 • Number of events 1 • 1 year
General disorders Dizziness	9.5% 2/21 • Number of events 2 • 1 year	0.00% 0/18 • 1 year	4.8% 1/21 • Number of events 1 • 1 year
General disorders Fever	9.5% 2/21 • Number of events 2 • 1 year	0.00% 0/18 • 1 year	0.00% 0/21 • 1 year
General disorders Headache	4.8% 1/21 • Number of events 1 • 1 year	0.00% 0/18 • 1 year	9.5% 2/21 • Number of events 2 • 1 year
Musculoskeletal and connective tissue disorders Limb pain	0.00% 0/21 • 1 year	5.6% 1/18 • Number of events 1 • 1 year	4.8% 1/21 • Number of events 1 • 1 year

Additional Information

Stephen R. Marder

Semel Institute at UCLA

Phone: 310-268-3647

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place