Long-Term Efficacy and Safety of Asenapine Using Haloperidol as a Positive Control (41513)(COMPLETED)(P05785)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00156065
First received: September 7, 2005
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

Schizophrenia is a brain disease. The primary features of schizophrenia are characterized by Positive symptoms (symptoms that should not be there, inability to think clearly, to distinguish reality from fantasy i.e., hearing voices) and Negative symptoms (a reduction or absence of normal behaviors or emotions, i.e., unable to manage emotions, make decisions and relate to others). Other symptoms include reduced ability to recall and learn new information, difficulty with problem solving, or maintaining productive employment. The symptoms of schizophrenia may be due to an imbalance in chemicals in the brain, primarily dopamine and serotonin, which enables brain cells to communicate with each other.

The clinical development of asenapine, as described in the 2007 IDB appears to have antipsychotic activity with superior symptomatic control compared to placebo and an improved safety profile compared to currently available neuroleptics. Its fast dissolving formulation may further add to treatment compliance. While various titration schedules have been used in previous studies, dose increases at 5 mg BID (twice daily) up to 10 mg BID have been well tolerated. Therefore, further exploration in a larger group of subjects with acute exacerbation of schizophrenia using an asenapine flexible dosing design ( 5 or 10 mg BID) will mimic actual clinical practice in a long-term 52-week extension trial.


Condition Intervention Phase
Schizophrenia
Drug: Haloperidol
Drug: Asenapine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Flexible-Dose, Long-Term Extension Trial of the Safety and Maintenance of Effect of Asenapine Using Haloperidol Positive Control in Subjects Who Complete Protocol 041023 [NCT00156104]

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Loss of Effect Over Time [ Time Frame: Throughout the 52 weeks of the trial. ] [ Designated as safety issue: Yes ]

    Loss of effect in subjects who had >=30% decrease from baseline in Positive and Negative Syndrome Scale (PANSS) score at the end of the original trial (NCT00156104) preceding the long-term extension.

    PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity.

    Loss of effect = increase in total PANSS >=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score >=6; discontinuation for lack of efficacy.


  • Median Survival Time of Effect [ Time Frame: 52 Weeks ] [ Designated as safety issue: Yes ]

    Kaplan-Meier estimate of median time to loss of effect in subjects who had >=30% decrease from baseline in PANSS score at the end of the original trial (NCT00156104) preceding the long-term extension.

    PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity.

    Loss of effect = increase in total PANSS >=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score >=6; discontinuation for lack of efficacy.



Enrollment: 187
Study Start Date: September 2005
Study Completion Date: October 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Haloperidol/Haloperidol
Haloperidol in original study (NCT00156104) and in current long-term extension.
Drug: Haloperidol
2-8 mg BID
Experimental: Asenapine/Asenapine
Asenapine in original study and asenapine in current long-term extension.
Drug: Asenapine
5 or 10 mg BID
Experimental: Placebo/Asenapine
Double-Blind subjects randomized to only placebo medication for 6 weeks in the short-term 041023 asenapine trial, were randomized (double-blind) into the long-term 041513 asenapine extension trial and received asenapine 5 mg BID for Week 1. After Week 1, subjects received asenapine (either 5 mg BID or 10 mg BID) for the remainder of the 52-week trial.
Drug: Asenapine
5 or 10 mg BID

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Completed the short-term 041023 trial (NCT00156104)
  • Continued to meet all demographic and procedural inclusion criteria of the short-term trial upon entry into this long-term extension trial
  • Sign a written informed consent for the 041513 trial.
  • Demonstrated an acceptable degree of compliance with trial medication in the short-term trials in the opinion of the investigator

Exclusion Criteria:

  • CGI-S (Clinical Global Impressions of Severity of Illness) score of greater than or equal to 6 (severely psychotic)
  • Occurrence(s) of AEs (adverse events) or other clinically significant findings that would prohibit their continuation
  • Met any of exclusion criteria regarding medical/psychiatric status listed in the 041023 short-term trial
  • Met exclusion criteria for medication status in short-term trials except for antidepressants and mood stabilizers.
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00156065     History of Changes
Other Study ID Numbers: P05785, Hera;, 41513
Study First Received: September 7, 2005
Results First Received: February 24, 2010
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Haloperidol
Haloperidol decanoate
Asenapine
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
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents

ClinicalTrials.gov processed this record on July 26, 2014