CompletedNCT00506077Updated Aug 3, 2015Results posted

MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia (0249-016)

A Phase 2 interventional study of MK0249 and Comparator: Placebo (unspecified) in Paranoid Schizophrenia, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 21 Years to 55 Years. Per ClinicalTrials.gov, last updated 2015-08-03.

Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 55
Allocation: Randomized
Ages: 21 Years to 55 Years
Sex: All

Study summary

The purpose of this study is to determine the safety and effectiveness of an investigational drug MK0249 for the treatment of the cognitive impairment in patients with schizophrenia.

Conditions studied

Paranoid Schizophrenia

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Keywords

Undifferentiated schizophrenia
residual schizophrenia

In context

Schizophrenia

3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.

This study's enrollment of 55 is below the median of 70 across 2,872 interventional studies indexed under Schizophrenia.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 21 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patient is clinically stable, on current antipsychotic medication for at least 3 months and current dose for 2 months
Patient has a 6th grade reading level or better
Females are not pregnant, and those who can have children agree to remain abstinent or use acceptable birth control throughout the study
Patient has had a stable living arrangement for at least 3 months prior to study start
Patient is in general good health based on screening assessments
Patient has total Positive and Negative Syndrome Scale (PANSS) score between 36 and 75 at screening and at the first baseline visit
Patient has a Clinical Global Impressions - Severity (CGI-S) score less than or equal to 4 at screening and at the first baseline visit

Exclusion criteria

Exclusion Criteria:

Patient has a major disease/disorder that may interfere with cognitive testing (such as mental retardation) and/or pose a risk upon study participation
Patient has a history of head trauma with loss of consciousness greater than 15 minutes
Patient has had warfarin treatment, MAO inhibitors, clonazepam or clozapine within 1 month of screening
Patient has had ECT treatment within 6 months of screening
Patient requires treatment with antihistamines or certain other medications listed in the protocol
Patient has a history of liver disease that has been active within the last 2 years, or a history of cancer within the past 5 years
Patient has a history of alcohol or drug dependence within the past year or alcohol or drug abuse within 3 months of screening

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Double (Participant, Investigator)
Enrollment: 55 participants (actual)

Study arms

Experimental
MK0249
Drug: MK0249
Placebo comparator
Placebo
Drug: Comparator: Placebo (unspecified)

Interventions

DrugMK0249
MK0249 10mg (2 x 5 mg) tablet daily (qd) for 28 days.
DrugComparator: Placebo (unspecified)
MK0249 10mg (2 x 5 mg) Pbo tablet qd for a 28 day treatment period.

What researchers measure

Primary outcomes

Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.
The mean change from baseline after 4 weeks of treatment in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance.
Time frame: Baseline and 4 weeks of treatment

Secondary outcomes

Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score
The Attention/Processing Speed Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Penn Continuous Performance Test (PCPT) and BACS battery Symbol Coding. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -91 and 91, respectively. Higher values (positive changes from baseline) indicate better performance.
Time frame: Baseline and 4 weeks of treatment
Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score
The Episodic Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Face Memory and BACS battery Verbal Memory. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -202 and 202, respectively. Higher values (positive changes from baseline) indicate better performance.
Time frame: Baseline and 4 weeks of treatment
Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score
The Working Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological (CNP) battery N-back test and the BACS battery Digit Sequencing test. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -122 and 122, respectively. Higher values (positive changes from baseline) indicate better performance.
Time frame: Baseline and 4 weeks of treatment

Other outcomes

Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.
Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).
Time frame: Pre-randomization Baseline
Pre-randomization Baseline: Attention/Processing Speed Composite Score
Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).
Time frame: Pre-randomization Baseline
Pre-randomization Baseline: Episodic Memory Composite Score
Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).
Time frame: Pre-randomization Baseline
Pre-randomization Baseline: Working Memory Composite Score
Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).
Time frame: Pre-randomization Baseline

Results

Posted Mar 7, 2011

Participant flow

First Patient Dosed: 11 February 2008; Last Patient Last Treatment: 08 October 2008. Six ex-U.S. study centers (3 Russia, 3 India).

Treatment Period 1

Participant flow — Treatment Period 1
Milestone	MK0249 Then Placebo	Placebo Then MK0249
Started	28	27
Completed	24	24
Not completed	4	3
Withdrew: Adverse event	2	1
Withdrew: Lost to follow-up	0	2
Withdrew: Withdrawal by subject	2	0

Washout

Participant flow — Washout
Milestone	MK0249 Then Placebo	Placebo Then MK0249
Started	24	24
Completed	24	24
Not completed	0	0

Treatment Period 2

Participant flow — Treatment Period 2
Milestone	MK0249 Then Placebo	Placebo Then MK0249
Started	24	24
Completed	23	23
Not completed	1	1
Withdrew: Adverse event	0	1
Withdrew: Withdrawal by subject	1	0

Outcome measures

PrimaryMean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.

The mean change from baseline after 4 weeks of treatment in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance.

Time frame:: Baseline and 4 weeks of treatment
Reported as:: Least squares mean · Composite T-score

Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.
Composite T-score	MK0249	Placebo
Mean Change From Baseline at 4 Weeks of Treatment in Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.	0.4 (-1.2 to 2.1)	0.5 (-1.1 to 2.2)

Statistical analysis

MK0249 vs Placebo · constrained longitudinal data analysis · p = 0.939 (The Benjamini \& Hochberg False Discovery Rate (FDR) approach at critical value 0.05 was used among 1 primary and 3 secondary cognition efficacy endpoints to control the false positive rate.)The model factors were treatment, sequence, period, week (as categorical variable), site, treatment-by-week, sequence-by-week, and period-by-week.

SecondaryMean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score

The Attention/Processing Speed Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Penn Continuous Performance Test (PCPT) and BACS battery Symbol Coding. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -91 and 91, respectively. Higher values (positive changes from baseline) indicate better performance.

Time frame:: Baseline and 4 weeks of treatment
Reported as:: Least squares mean · Composite T-score

Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score
Composite T-score	MK0249	Placebo
Mean Change From Baseline at 4 Weeks of Treatment in Attention/Processing Speed Composite Score	0.5 (-0.4 to 1.5)	0.0 (-0.9 to 0.9)

Statistical analysis

MK0249 vs Placebo · constrained Longitudinal Data Analysis · p = 0.736 (P-Value Comments (limit 250 characters): The Benjamini \& Hochberg False Discovery Rate (FDR) approach at critical value 0.05 was used among 1 primary and 3 secondary cognition efficacy endpoints to control the false positive rate.)The model factors were treatment, sequence, period, week (as categorical variable), site, treatment-by-week, sequence-by-week, and period-by-week.

SecondaryMean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score

The Episodic Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological Battery (CNP) Face Memory and BACS battery Verbal Memory. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -202 and 202, respectively. Higher values (positive changes from baseline) indicate better performance.

Time frame:: Baseline and 4 weeks of treatment
Reported as:: Least squares mean · Composite T-score

Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score
Composite T-score	MK0249	Placebo
Mean Change From Baseline at 4 Weeks of Treatment in Episodic Memory Composite Score	0.9 (-0.9 to 2.6)	0.1 (-1.6 to 1.8)

Statistical analysis

MK0249 vs Placebo · constrained Longitudinal Data Analysis · p = 0.736 (The Benjamini \& Hochberg False Discovery Rate (FDR) approach at critical value 0.05 was used among 1 primary and 3 secondary cognition efficacy endpoints to control the false positive rate.)The model factors were treatment, sequence, period, week (as categorical variable), site, treatment-by-week, sequence-by-week, and period-by-week.

SecondaryMean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score

The Working Memory Composite Score was comprised of the University of Pennsylvania's Computerized Neuropsychological (CNP) battery N-back test and the BACS battery Digit Sequencing test. The composite score was calculated as a weighted average of the T-scores (normalized for age) for each test. The minimum and maximum values possible for this composite T-score of the change from baseline were -122 and 122, respectively. Higher values (positive changes from baseline) indicate better performance.

Time frame:: Baseline and 4 weeks of treatment
Reported as:: Least squares mean · Composite T-score

Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score
Composite T-score	MK0249	Placebo
Mean Change From Baseline at 4 Weeks of Treatment in Working Memory Composite Score	0.8 (-1.0 to 2.6)	-0.2 (-2.0 to 1.5)

Statistical analysis

MK0249 vs Placebo · constrained Logitudinal Data Analysis · p = 0.736 (The Benjamini \& Hochberg False Discovery Rate (FDR) approach at critical value 0.05 was used among 1 primary and 3 secondary cognition efficacy endpoints to control the false positive rate.)The model factors were treatment, sequence, period, week (as categorical variable), site, treatment-by-week, sequence-by-week, and period-by-week.

Other pre-specifiedPre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.

Pre-randomization baseline values for all treatment sequences are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).

Time frame:: Pre-randomization Baseline
Reported as:: Least squares mean · Composite T-score

Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.
Composite T-score	MK0249	Placebo
Pre-randomization Baseline: Total Cognitive Score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery.	40.5 ± 0.98	40.5 ± 0.98

Other pre-specifiedPre-randomization Baseline: Attention/Processing Speed Composite Score

Time frame:: Pre-randomization Baseline
Reported as:: Least squares mean · Composite T-score

Pre-randomization Baseline: Attention/Processing Speed Composite Score
Composite T-score	MK0249	Placebo
Pre-randomization Baseline: Attention/Processing Speed Composite Score	47.8 ± 0.73	47.8 ± 0.73

Other pre-specifiedPre-randomization Baseline: Episodic Memory Composite Score

Time frame:: Pre-randomization Baseline
Reported as:: Least squares mean · Composite T-score

Pre-randomization Baseline: Episodic Memory Composite Score
Composite T-score	MK0249	Placebo
Pre-randomization Baseline: Episodic Memory Composite Score	43.9 ± 1.16	43.9 ± 1.16

Other pre-specifiedPre-randomization Baseline: Working Memory Composite Score

Time frame:: Pre-randomization Baseline
Reported as:: Least squares mean · Composite T-score

Pre-randomization Baseline: Working Memory Composite Score
Composite T-score	MK0249	Placebo
Pre-randomization Baseline: Working Memory Composite Score	43.5 ± 0.98	43.5 ± 0.98

Adverse events

Collected over Patients were assessed for adverse events (AEs) from visit 2 (V2) (Day -7): Neuropsych Testing through visit 11 (V11) (Day 77): 2-week Follow-Up.. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
MK0249	—	0/52 (0%)	20/52 (38.5%)
Placebo	—	0/51 (0%)	15/51 (29.4%)

Most frequent other events

Showing 10 of 18

Most frequent other events
Event	MK0249	Placebo
insomniaPsychiatric disorders	7/52	4/51
headacheNervous system disorders	6/52	2/51
anxietyPsychiatric disorders	5/52	2/51
nauseaGastrointestinal disorders	4/52	3/51
irritabilityGeneral disorders	0/52	3/51
alanine aminotransferase increasedInvestigations	1/52	2/48
aspartate aminotransferase increasedInvestigations	0/52	2/48
white blood cell count increasedInvestigations	1/52	2/48
nasopharyngitisInfections and infestations	1/52	2/51
pain in extremityMusculoskeletal and connective tissue disorders	1/52	2/51

Baseline characteristics

Age, Continuous
Age, Continuous(years)	MK0249 Then Placebo	Placebo Then MK0249	Total
Mean	30.7 ± 7.5	32.5 ± 8.4	31.6 ± 7.9

Sex: Female, Male
Sex: Female, Male(Participants)	MK0249 Then Placebo	Placebo Then MK0249	Total
Female	8	7	15
Male	20	20	40

Study locations

No study locations are listed for this record.

References and documents

Publications

F Egan M, Zhao X, Gottwald R, Harper-Mozley L, Zhang Y, Snavely D, Lines C, Michelson D. Randomized crossover study of the histamine H3 inverse agonist MK-0249 for the treatment of cognitive impairment in patients with schizophrenia. Schizophr Res. 2013 May;146(1-3):224-30. doi: 10.1016/j.schres.2013.02.030. Epub 2013 Mar 22. PubMed 23523692 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 3, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00506077
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Jul 25, 2007
Start date: Dec 2007
Primary completion: Oct 2008
Completion: Oct 2008
Results posted: Mar 7, 2011
Last update: Aug 3, 2015

Study contacts

Medical Monitor

study director · Merck Sharp & Dohme LLC

View the source record on ClinicalTrials.gov ↗

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MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia (0249-016)

Study summary

Conditions studied

Browse trials for

Keywords

In context

Schizophrenia

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Other outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

References and documents

Publications

Updates

Registry details

Key details

Study contacts

Not currently enrolling

Follow this study

Discussion

Other studies in this condition

Other studies from this sponsor

Inclusion criteria

Exclusion criteria