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

NCT00827918 | Completed Phase 2 Results DMC

• 2 other identifiers: 8998-0042009_519
• Study Type: interventional
• Target: 216
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Schizophrenia

Keywords

Acute Exacerbation of Schizophrenia

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline and Week 4

• 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.

  Up to 6 Weeks

• 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.

  Up to 4 Weeks

Secondary Outcomes (4)

• Percentage of Participants With Response at Week 4

  Week 4

• Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) at Week 4

  Baseline and Week 4

• Mean Change From Baseline in PANSS Positive Subscale at Week 4

  Baseline and Week 4

• Mean Change From Baseline in PANSS Negative Subscale at Week 4

  Baseline and Week 4

Study Arms (3)

MK-8998

EXPERIMENTAL

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

Olanzapine

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Placebo Comparator to MK-8998 or olanzapine

Drug: Comparator: Placebo

Interventions

MK-8998 DRUG

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.

MK-8998

Comparator: Olanzapine DRUG

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.

Olanzapine

Comparator: Placebo DRUG

Placebo tablets matching olanzapine tablets and MK-8998 capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 23532746 DERIVED

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2009
• First Posted: January 23, 2009
• Study Start: March 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: October 21, 2015
• Results First Posted: February 6, 2014

Record last verified: 2015-10