Long-Term Efficacy and Safety of Asenapine Using Olanzapine as a Positive Control (41512)(COMPLETED)(P05784)

This study has been completed.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
First received: September 8, 2005
Last updated: August 10, 2015
Last verified: August 2015

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 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
Drug: Olanzapine
Drug: Asenapine
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety 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 Olanzapine Positive Control in Subjects Who Complete Protocols 041021 or 041022.

Resource links provided by NLM:

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

Primary Outcome Measures:
  • To assess long-term safety including overall symptoms (AEs; SAEs); Vital signs; ISST; EPS; and maintenance of effect; for asenapine with haloperidol control. [ Time Frame: Weeks 1;2; 4; 8; 12; 16; 24; 32; 40; 52 (Endpoint) ] [ Designated as safety issue: Yes ]
  • Quality of Life and Patient Functionality (QLS; Q-LES-Q and PETIT) [ Time Frame: Weeks 16; 32; 52(Endpoint) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pregnancy tests; Lab tests [ Time Frame: Weeks 8; 16; 32; 52 (Endpoint) ] [ Designated as safety issue: Yes ]
  • Physical exams [ Time Frame: Week 12; 24; 52 (Endpoint) ] [ Designated as safety issue: Yes ]
  • Neurocognition and cognitive functioning [ Time Frame: Weeks 24 and 52 (Endpoint) ] [ Designated as safety issue: Yes ]
  • Weight and abdominal girth [ Time Frame: Weeks 4;8;12; 16; 24; 32;40;52(Endpoint) ] [ Designated as safety issue: Yes ]
  • ECGs [ Time Frame: Weeks 2;4;8;24;52(Endpoint) ] [ Designated as safety issue: Yes ]
  • Depression (CDSS) [ Time Frame: Weeks 12; 24; 52 (Endpoint) ] [ Designated as safety issue: Yes ]

Enrollment: 260
Study Start Date: April 2005
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Olanzapine 20 mg QD
Drug: Olanzapine
5- 20 mg QD
Experimental: 2
Asenapine 5 or 10 mg BID
Drug: Asenapine
5 or 10 mg BID
Double-Blind subjects randomized to only placebo medication for 6 weeks in the short-term 041021 or 041022 asenapine trials, were randomized (double-blind) Into the long-term 041512 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.
Other: Placebo


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

Inclusion Criteria:

  • Completed the short-term trial ( 041021 or 021022)
  • 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 041512 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 score of greater or equal to 6 ( severely psychotic)
  • Occurrence(s) of AE or other clinically significant findings that would prohibit their continuation
  • Met any of exclusion criteria regarding medical/psychiatric status listed in the short-term trials ( 041021 or 041022)
  • Met exclusion criteria for medication status in short-term trials except for antidepressants and mood stabilizers.
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  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00156091     History of Changes
Other Study ID Numbers: P05784  Hera;  41512 
Study First Received: September 8, 2005
Last Updated: August 10, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on May 02, 2016