A Study to Test the Safety and Efficacy of MK-8998 in Acutely Psychotic Participants With Schizophrenia (MK-8998-004)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00827918
First received: January 22, 2009
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: MK-8998
Drug: Comparator: Olanzapine
Drug: Comparator: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 6 Weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 4 Weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 216
Study Start Date: March 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8998
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
Drug: MK-8998
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.
Active Comparator: Olanzapine
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
Drug: Comparator: Olanzapine
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.
Placebo Comparator: Placebo
Placebo Comparator to MK-8998 or olanzapine
Drug: Comparator: Placebo
Placebo tablets matching olanzapine tablets and MK-8998 capsules

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827918

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00827918     History of Changes
Other Study ID Numbers: 8998-004, 2009_519
Study First Received: January 22, 2009
Results First Received: September 24, 2013
Last Updated: June 16, 2014
Health Authority: Serbia and Montenegro: Agency for Drugs and Medicinal Devices

Keywords provided by Merck Sharp & Dohme Corp.:
Acute Exacerbation of Schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Olanzapine
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on August 18, 2014