Clinical trial NCT01617187: A Study of the Efficacy and Safety of Asenapine in Participants With an Acute Exacerbation of Schizophrenia (P05688)
Official title: A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2012-06-12
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to assess the effect of asenapine 2.5 and 5 mg sublingually twice daily (BID) compared with placebo in the treatment of schizophrenia (overall symptoms) as measured by the Positive and Negative Syndrome Scale (PANSS). Olanzapine administered 15 mg orally once daily (QD) was used as an active control. The primary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in the PANSS total score at Day 42. The first key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in Clinical Global Impression Scale-Severity (CGI-S) score at Day 42. The second key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the rate of PANSS responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42.

Detailed description: The trial consists of a screening/tapering period, treatment period, and follow-up period. The 6-week active treatment period includes an inpatient phase and outpatient phase. Participants who complete the trial may continue treatment under a long-term extension protocol (P05689). Participants who do not continue in the treatment continuation trial (whether they complete the 6-week trial or discontinue prematurely) will have a follow-up visit 7 days after their last dose of trial medication.

Eligibility criteria: Inclusion Criteria:

* Current diagnosis of schizophrenia of paranoid, disorganized, or undifferentiated subtype
* Minimum PANSS total score of 70 at Screening and Baseline
* Score of at least 4 (moderate) in two or more of the five items in the positive subscale of the PANSS
* Confirmed to be experiencing an acute exacerbation of schizophrenia
* CGI-S scale score of at least 4 (moderately ill) at Baseline
* Has responded positively to an antipsychotic medication other than clozapine (Clozaril®) in a prior episode

Exclusion Criteria:

* Body mass index (BMI) \<18.5 or \>40.0 kg/m\^2
* Laboratory and/or clinical evidence of clinically significant hepatic conditions
* Known history of, or undergoing treatment for, narrow angle glaucoma
* Diagnosed with epilepsy or has had any seizure disorder beyond childhood febrile seizures
* Known serological evidence of human immunodeficiency virus (HIV) antibody
* History of neuroleptic malignant syndrome or tardive dyskinesias
* Past or current diagnosis of schizoaffective disorder, schizophrenia of residual subtype, schizophrenia of catatonic subtype, current diagnosis of schizophrenia with course specifiers continuous, single episode in partial remission, or single episode in full remission, or borderline personality disorder

Primary outcomes:
measure: Change From Baseline in PANSS Total Score at Day 42
timeFrame: Baseline and Day 42
Secondary outcomes:
measure: Change From Baseline in CGI-S Score at Day 42
timeFrame: Baseline and Day 42
measure: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in Body Weight at Day 42
timeFrame: Baseline and Day 42
measure: Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35
timeFrame: Baseline and Days 4, 7, 14, 21, 28 and 35
measure: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35
timeFrame: Days 4, 7, 14, 21, 28 and 35
measure: Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35
timeFrame: Baseline and Days 4, 7, 14, 21, 28 and 35
measure: Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
measure: Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42
timeFrame: Baseline and Days 4, 7, 14, 21, 28, 35 and 42
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Landbloom R, Mackle M, Wu X, Kelly L, Snow-Adami L, McIntyre RS, Mathews M, Hundt C. Asenapine for the treatment of adults with an acute exacerbation of schizophrenia: results from a randomized, double-blind, fixed-dose, placebo-controlled trial with olanzapine as an active control. CNS Spectr. 2017 Aug;22(4):333-341. doi: 10.1017/S1092852916000377. Epub 2016 Nov 8.