A Study to Test the Safety and Efficacy of MK-8998 in Acutely Psychotic Participants With Schizophrenia (MK-8998-004)
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MK-8998
Comparator: Olanzapine
Comparator: Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Acute Exacerbation of Schizophrenia
Eligibility Criteria
Inclusion Criteria:
- Patient's age is 18 to 55
- Patient meets DSM-IV/DSM-IV-TR criteria for a primary diagnosis of schizophrenia
- The duration of the patients schizophrenia diagnosis must be greater than 1 year
- Patient has an acute exacerbation of psychotic symptoms (of at least 3 days but no longer than 6 weeks) and marked deterioration of function
Exclusion Criteria:
- Patient currently has a clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder that would pose a risk to the patient in the opinion of the investigator if they were to participate in the study or that might confound the results of the study
- The patient has evidence of acute hepatitis, clinically significant chronic hepatitis, or impaired hepatic function
- The patient has a chronic organic disease of the central nervous system (other than schizophrenia) such as, tumors, inflammation, active seizure disorder, vascular disorder, Parkinson's disease, Alzheimer's disease or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, patients must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury
- Patient has a history of alcohol/drug dependence within 3 months or alcohol/drug abuse within 1 month of screening. Exceptions include caffeine and nicotine abuse/dependence
- Patient has a history of hypersensitivity to olanzapine OR poor response to olanzapine in the last 2 years OR intolerable side effects due to olanzapine OR patients current psychotic relapse occurred while consistently taking a therapeutic dose (10 mg or more) of olanzapine OR olanzapine is medically contradicted
- Patient is refractory to antipsychotic treatment
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
MK-8998
Olanzapine
Placebo
Arm Description
MK-8998, 6 mg twice a day (BID) for Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period
Olanzapine, 5 mg BID for Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period
Placebo Comparator to MK-8998 or olanzapine
Outcomes
Primary Outcome Measures
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4
PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales.
Number of Participants Who Experienced at Least One Adverse Event
An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.
Secondary Outcome Measures
Percentage of Participants With Response at Week 4
Responders were defined as participants who demonstrated ≥ 20% improvement from baseline on the PANSS total score. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales.
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4
CGI-S is a commonly used measure of symptom severity in treatment studies of participants with mental disorders. CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill.
Mean Change From Baseline in PANSS Positive Subscale at Week 4
PANSS Positive scale assesses hallucinations, delusions and related symptoms. The Positive scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49.
Mean Change From Baseline in PANSS Negative Subscale at Week 4
PANSS Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms. The Negative scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49.
Full Information
NCT ID
NCT00827918
First Posted
January 22, 2009
Last Updated
October 20, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00827918
Brief Title
A Study to Test the Safety and Efficacy of MK-8998 in Acutely Psychotic Participants With Schizophrenia (MK-8998-004)
Official Title
A Phase IIa, Randomized, Multicenter, Double-Blind, Active Comparator- and Placebo-Controlled, Clinical Trial to Study the Safety and Efficacy of MK8998 in Acutely Psychotic Patients With Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A study to evaluate the safety and efficacy of treatment with MK-8998 as compared to placebo and olanzapine for acutely psychotic patients with schizophrenia. The primary hypothesis is that in participants undergoing an acute psychotic episode of schizophrenia, MK-8998 6 to 8 mg twice daily is superior to placebo in the treatment of symptoms of schizophrenia as measured by the mean change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Week 4.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Acute Exacerbation of Schizophrenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
216 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-8998
Arm Type
Experimental
Arm Description
MK-8998, 6 mg twice a day (BID) for Days 1 to 7, and 8 mg BID thereafter for a 4-week total treatment period
Arm Title
Olanzapine
Arm Type
Active Comparator
Arm Description
Olanzapine, 5 mg BID for Day 1 to 7, and 15 mg (5 mg in the morning and 10 mg in the evening) thereafter for a 4-week total treatment period
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo Comparator to MK-8998 or olanzapine
Intervention Type
Drug
Intervention Name(s)
MK-8998
Intervention Description
MK-8998 6 mg capsules twice daily with food on Days 1 through 7. On Day 8, dosage will be increased to 8 mg capsules twice daily. Treatment period is 4 weeks. There will be a period of time when all participants will receive placebo.
Intervention Type
Drug
Intervention Name(s)
Comparator: Olanzapine
Intervention Description
Olanzapine 5 mg tablets twice daily with food on Days 1 through 7. On Day 8, dosage will be increased to 5 mg tablets in the morning and 10 mg tablets in the evening. Treatment period is 4 weeks. There will be a period of time when all participants will receive placebo.
Intervention Type
Drug
Intervention Name(s)
Comparator: Placebo
Intervention Description
Placebo tablets matching olanzapine tablets and MK-8998 capsules
Primary Outcome Measure Information:
Title
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4
Description
PANSS is a medical scale used for measuring symptom severity of participants with schizophrenia. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales.
Time Frame
Baseline and Week 4
Title
Number of Participants Who Experienced at Least One Adverse Event
Description
An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.
Time Frame
Up to 6 Weeks
Title
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Description
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.
Time Frame
Up to 4 Weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With Response at Week 4
Description
Responders were defined as participants who demonstrated ≥ 20% improvement from baseline on the PANSS total score. PANSS measure is composed of 3 scales: Positive scale, Negative scale, and General Psychopathology scale. Positive scale assesses hallucinations, delusions and related symptoms; Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms; and General Psychopathology scale addresses other symptoms such as anxiety, somatic concern and disorientation. The PANSS has 30 items in its 3 scales and an anchored Likert scale from 1 to 7 is used to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. The Positive scale has 7 items with a score from 7 to 49, the Negative scale has 7 items with a score from 7 to 49, and the General Psychopathology scale has 16 items with a score from 16 to 112. A total score is the sum of the 3 scores for the 3 scales.
Time Frame
Week 4
Title
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4
Description
CGI-S is a commonly used measure of symptom severity in treatment studies of participants with mental disorders. CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill.
Time Frame
Baseline and Week 4
Title
Mean Change From Baseline in PANSS Positive Subscale at Week 4
Description
PANSS Positive scale assesses hallucinations, delusions and related symptoms. The Positive scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49.
Time Frame
Baseline and Week 4
Title
Mean Change From Baseline in PANSS Negative Subscale at Week 4
Description
PANSS Negative scale assesses emotional withdrawal, lack of motivation, and similar symptoms. The Negative scale has 7 items with an anchored Likert scale from 1 to 7 to score each item. Values of 2 and above indicate the presence of progressively more severe symptoms. A total score ranges from 7 to 49.
Time Frame
Baseline and Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient's age is 18 to 55
Patient meets DSM-IV/DSM-IV-TR criteria for a primary diagnosis of schizophrenia
The duration of the patients schizophrenia diagnosis must be greater than 1 year
Patient has an acute exacerbation of psychotic symptoms (of at least 3 days but no longer than 6 weeks) and marked deterioration of function
Exclusion Criteria:
Patient currently has a clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder that would pose a risk to the patient in the opinion of the investigator if they were to participate in the study or that might confound the results of the study
The patient has evidence of acute hepatitis, clinically significant chronic hepatitis, or impaired hepatic function
The patient has a chronic organic disease of the central nervous system (other than schizophrenia) such as, tumors, inflammation, active seizure disorder, vascular disorder, Parkinson's disease, Alzheimer's disease or other forms of dementia, myasthenia gravis, or other degenerative processes. In addition, patients must not have a history of mental retardation or persistent neurological symptoms attributable to serious head injury
Patient has a history of alcohol/drug dependence within 3 months or alcohol/drug abuse within 1 month of screening. Exceptions include caffeine and nicotine abuse/dependence
Patient has a history of hypersensitivity to olanzapine OR poor response to olanzapine in the last 2 years OR intolerable side effects due to olanzapine OR patients current psychotic relapse occurred while consistently taking a therapeutic dose (10 mg or more) of olanzapine OR olanzapine is medically contradicted
Patient is refractory to antipsychotic treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
23532746
Citation
Egan MF, Zhao X, Smith A, Troyer MD, Uebele VN, Pidkorytov V, Cox K, Murphy M, Snavely D, Lines C, Michelson D. Randomized controlled study of the T-type calcium channel antagonist MK-8998 for the treatment of acute psychosis in patients with schizophrenia. Hum Psychopharmacol. 2013 Mar;28(2):124-33. doi: 10.1002/hup.2289.
Results Reference
derived
Learn more about this trial
A Study to Test the Safety and Efficacy of MK-8998 in Acutely Psychotic Participants With Schizophrenia (MK-8998-004)
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