Trial Outcomes & Findings for Treatment of Cognitive Impairment in Men With Schizophrenia (MK5757-005)(COMPLETED) (NCT NCT00848484)

Last Updated: 2015-11-02

Results Overview

The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive impairment, as measured by the mean change from baseline after 2 weeks of treatment in the composite score. The BACS composite score was calculated by averaging scores from the BACS subtests, including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Verbal Fluency (Semantic Fluency and Letter Fluency) and Tower of London. The possible minimum and maximum scores for change from baseline at two weeks of treatment for the endpoint are -111.5 and 111.5, respectively.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Baseline and Week 2

Results posted on

2015-11-02

Participant Flow

First Patient Evaluated: 14-Oct-2008, Last Patient Last Visit: 18-Jun-2009; 6 sites (2 United States, 4 Russia). In total, enrollment lasted approximately 8 months.

Patients in this cross-over study were randomly assigned to placebo or MK5757 for 2 weeks separated by a 2-week wash-out period. Women were not permitted to enroll into this study because safety, pharmacokinetic or pharmacodynamic properties of MK5757 in women have not been established.

Participant milestones

Participant milestones
Measure	MK5757 / Placebo Patients were randomly assigned to two weeks of treatment with MK5757 during Treatment Period 1 followed by a 2-week washout followed by administration of placebo during Treatment Period 2. Patients received one orally-administered three times a Day\[ter in die\] (tid) dose on the first day of each treatment period. Patients titrated to two orally-administered tid doses on the second day of each Treatment Period and had the option to down-dose to one tid dose for the remainder of that treatment period. Patients who down-dosed during Treatment Period 1 titrated to the target dose of 50 mg tid (or the placebo equivalent) during Treatment Period 2, but were permitted to down-dose if necessary. A 14-day Washout Period separated each 14-day treatment period	Placebo / MK5757 Patients were randomly assigned to two weeks of treatment with placebo during Treatment Period 1 followed by a 2-week washout followed by administration of MK5757 during Treatment Period 2. Patients received one orally-administered three times a Day\[ter in die\] (tid) dose on the first day of each treatment period. Patients titrated to two orally-administered tid doses on the second day of each Treatment Period and had the option to down-dose to one tid dose for the remainder of that treatment period. Patients who down-dosed during Treatment Period 1 titrated to the target dose of 50 mg tid (or the placebo equivalent) during Treatment Period 2, but were permitted to down-dose if necessary. A 14-day Washout Period separated each 14-day treatment period
First Intervention (Treatment Period 1) STARTED	27	27
First Intervention (Treatment Period 1) With Reduced Dose at Treatment Period 1	2	1
First Intervention (Treatment Period 1) COMPLETED	25	24
First Intervention (Treatment Period 1) NOT COMPLETED	2	3
Washout Period of Two Weeks STARTED	25	24
Washout Period of Two Weeks COMPLETED	25	21
Washout Period of Two Weeks NOT COMPLETED	0	3
Second Intervention (Treatment Period 2) STARTED	25	21
Second Intervention (Treatment Period 2) With Reduced Dose at Treatment Period 2	0	0
Second Intervention (Treatment Period 2) COMPLETED	25	20
Second Intervention (Treatment Period 2) NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	MK5757 / Placebo Patients were randomly assigned to two weeks of treatment with MK5757 during Treatment Period 1 followed by a 2-week washout followed by administration of placebo during Treatment Period 2. Patients received one orally-administered three times a Day\[ter in die\] (tid) dose on the first day of each treatment period. Patients titrated to two orally-administered tid doses on the second day of each Treatment Period and had the option to down-dose to one tid dose for the remainder of that treatment period. Patients who down-dosed during Treatment Period 1 titrated to the target dose of 50 mg tid (or the placebo equivalent) during Treatment Period 2, but were permitted to down-dose if necessary. A 14-day Washout Period separated each 14-day treatment period	Placebo / MK5757 Patients were randomly assigned to two weeks of treatment with placebo during Treatment Period 1 followed by a 2-week washout followed by administration of MK5757 during Treatment Period 2. Patients received one orally-administered three times a Day\[ter in die\] (tid) dose on the first day of each treatment period. Patients titrated to two orally-administered tid doses on the second day of each Treatment Period and had the option to down-dose to one tid dose for the remainder of that treatment period. Patients who down-dosed during Treatment Period 1 titrated to the target dose of 50 mg tid (or the placebo equivalent) during Treatment Period 2, but were permitted to down-dose if necessary. A 14-day Washout Period separated each 14-day treatment period
First Intervention (Treatment Period 1) Adverse Event	2	1
First Intervention (Treatment Period 1) Physician Decision	0	1
First Intervention (Treatment Period 1) Withdrawal by Subject	0	1
Washout Period of Two Weeks Withdrawal by Subject	0	3
Second Intervention (Treatment Period 2) Lost to Follow-up	0	1

Baseline Characteristics

Treatment of Cognitive Impairment in Men With Schizophrenia (MK5757-005)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK5757 / Placebo n=27 Participants Patients were randomly assigned to two weeks of treatment with MK5757 during Treatment Period 1 followed by a 2-week washout followed by administration of placebo during Treatment Period 2. Patients received one orally-administered three times a Day\[ter in die\] (tid) dose on the first day of each treatment period. Patients titrated to two orally-administered tid doses on the second day of each Treatment Period and had the option to down-dose to one tid dose for the remainder of that treatment period. Patients who down-dosed during Treatment Period 1 titrated to the target dose of 50 mg tid (or the placebo equivalent) during Treatment Period 2, but were permitted to down-dose if necessary. A 14-day Washout Period separated each 14-day treatment period	Placebo / MK5757 n=27 Participants Patients were randomly assigned to two weeks of treatment with placebo during Treatment Period 1 followed by a 2-week washout followed by administration of MK5757 during Treatment Period 2. Patients received one orally-administered three times a Day\[ter in die\] (tid) dose on the first day of each treatment period. Patients titrated to two orally-administered tid doses on the second day of each Treatment Period and had the option to down-dose to one tid dose for the remainder of that treatment period. Patients who down-dosed during Treatment Period 1 titrated to the target dose of 50 mg tid (or the placebo equivalent) during Treatment Period 2, but were permitted to down-dose if necessary. A 14-day Washout Period separated each 14-day treatment period	Total n=54 Participants Total of all reporting groups
Age, Continuous	33.8 years STANDARD_DEVIATION 8.5 • n=99 Participants	36.1 years STANDARD_DEVIATION 9.1 • n=107 Participants	35.0 years STANDARD_DEVIATION 8.8 • n=206 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Male	27 Participants n=99 Participants	27 Participants n=107 Participants	54 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=99 Participants	27 Participants n=107 Participants	51 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized Black or African American	6 participants n=99 Participants	7 participants n=107 Participants	13 participants n=206 Participants
Race/Ethnicity, Customized Multi-Racial	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized White	20 participants n=99 Participants	20 participants n=107 Participants	40 participants n=206 Participants
Study Region United States	8 participants n=99 Participants	7 participants n=107 Participants	15 participants n=206 Participants
Study Region Russia	19 participants n=99 Participants	20 participants n=107 Participants	39 participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline and Week 2

Population: Full Analysis Set (FAS): The FAS population was a subset of all randomized patients which included randomized patients who received at least one dose of study treatment and had at least one measurement in any of the two treatment periods.

Outcome measures

Outcome measures
Measure	MK5757 n=42 Participants MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=46 Participants Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Mean Change From Baseline in the Composite Score From the Brief Assessment of Cognition in Schizophrenia (BACS) Battery After 2 Weeks of Treatment	0.3 T-score based on normative data Interval -1.2 to 1.7	1.5 T-score based on normative data Interval 0.1 to 2.8

SECONDARY outcome

Timeframe: Baseline and week 2

CogState Schizophrenia Battery was used to evaluate cognitive impairment, as measured by the mean change from baseline after 2 weeks of treatment in the composite score. The composite score was comprised of 4 modules from the CogState Schizophrenia Battery: Identification Task, Detection Task, One Card Learning Task and Groton Maze Learning Task. Composite score was calculated by averaging all available standardized tests scores for the specified tests. The possible minimum and maximum scores for change from baseline at 2 weeks of treatment for the endpoint are -347.5 and 347.5, respectively.

Outcome measures

Outcome measures
Measure	MK5757 n=42 Participants MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=46 Participants Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Mean Change From Baseline After 2 Weeks of Treatment in the CogState Composite Score	0.3 T-score based on normative data Interval -1.7 to 2.4	-0.5 T-score based on normative data Interval -2.5 to 1.5

SECONDARY outcome

Timeframe: Baseline and Week 2

The Executive Functioning Composite Score was comprised of the following tests: Groton Maze Learning Task from the CogState Schizophrenia Battery and Tower of London, Semantic Fluency and Letter Fluency tests from the BACS. The composite score was calculated by averaging all of the available standardized tests scores for the specified tests. The possible minimum and maximum scores for change from baseline at two weeks of treatment for the endpoint are -253.4 and 253.4, respectively.

Outcome measures

Outcome measures
Measure	MK5757 n=42 Participants MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=46 Participants Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Mean Change From Baseline After 2 Weeks of Treatment in the Executive Functioning Composite Score	0.9 T-score based on normative data Interval -0.9 to 2.6	1.0 T-score based on normative data Interval -0.7 to 2.6

SECONDARY outcome

Timeframe: Baseline and Week 2

The Episodic Memory Composite Score was comprised of the following tests: Continuous Paired Associate Learning Task and One Card Learning Task from the CogState Schizophrenia Battery and the Verbal Memory test from the BACS. The composite score was calculated by averaging all of the available standardized tests scores for the specified tests. The possible minimum and maximum scores for change from baseline at two weeks of treatment for the endpoint are -207.06 and 207.06, respectively.

Outcome measures

Outcome measures
Measure	MK5757 n=42 Participants MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=46 Participants Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Mean Change From Baseline After 2 Weeks of Treatment in the Episodic Memory Composite Score	0.1 T-score based on normative data Interval -1.4 to 1.6	0.8 T-score based on normative data Interval -0.7 to 2.3

SECONDARY outcome

Timeframe: Baseline and Week 2

The Working Memory Composite Score was comprised of the following tests: Two-Back Memory Task from the CogState Schizophrenia Battery and the Digit Sequencing test from the BACS. The composite score was calculated by averaging all of the available standardized tests scores for the specified tests. The possible minimum and maximum scores for change from baseline at two weeks of treatment for the endpoint are -27.06 and 27.06, respectively.

Outcome measures

Outcome measures
Measure	MK5757 n=42 Participants MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=46 Participants Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Mean Change From Baseline After 2 Weeks of Treatment in the Working Memory Composite Score	-1.7 T-score based on normative data Interval -3.6 to 0.2	-0.1 T-score based on normative data Interval -1.9 to 1.7

SECONDARY outcome

Timeframe: Baseline and Week 2

The Attention/Processing Speed Composite Score was comprised of the following tests: Identification Task and the Detection Task from the CogState Schizophrenia Battery and the Symbol Coding test from the BACS. The composite score was calculated by averaging all of the available standardized tests scores for the specified tests. The possible minimum and maximum scores for change from baseline at two weeks of treatment for the endpoint are -287.15 and 287.15, respectively.

Outcome measures

Outcome measures
Measure	MK5757 n=42 Participants MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=46 Participants Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Mean Change From Baseline After 2 Weeks of Treatment in the Attention/Processing Speed Composite Score	-0.2 T-score based on normative data Interval -2.1 to 1.6	-1.3 T-score based on normative data Interval -3.1 to 0.4

Adverse Events

MK5757

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK5757 n=48 participants at risk MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=52 participants at risk Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Investigations Electrocardiogram QT prolonged	0.00% 0/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	1.9% 1/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK5757 n=48 participants at risk MK5757 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.	Placebo n=52 participants at risk Matching placebo 50 mg tid for Treatment Period 1 or Treatment Period 2 (depending on the sequence). Patients who were unable to tolerate 50 mg tid were allowed to titrate down to 25 mg tid and remained on 25 mg tid for the remainder of the treatment period.
Cardiac disorders Sinus bradycardia	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	3.8% 2/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Ear and labyrinth disorders Vertigo	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Gastrointestinal disorders Constipation	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Gastrointestinal disorders Nausea	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Infections and infestations Nasopharyngitis	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Investigations Electrocardiogram QT prolonged	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Investigations Electrocardiogram change	4.2% 2/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	1.9% 1/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Metabolism and nutrition disorders Type 2 diabetes mellitus	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Nervous system disorders Disturbance in attention	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Nervous system disorders Headache	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	5.8% 3/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Nervous system disorders Somnolence	4.2% 2/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Psychiatric disorders Agitation	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	1.9% 1/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Psychiatric disorders Anxiety	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Psychiatric disorders Insomnia	6.2% 3/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	3.8% 2/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Respiratory, thoracic and mediastinal disorders Hiccups	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	2.1% 1/48 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.	0.00% 0/52 • All clinical adverse events within 14 days post dose and all laboratory adverse events post dose are included. The number of patients listed in the Adverse Event tables is the number of patients who received study treatment and had follow-up.