Clinical trial NCT00159796: 3-week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07009)
Official title: A Phase III, Randomized, Placebo-Controlled, Double-Blind Trial Evaluating the Safety and Efficacy of Sublingual Asenapine vs. Olanzapine and Placebo in In-Patients With an Acute Manic Episode Clinical Trial Protocol 7501005 (Secondary Title: ARES)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2005-09-12
Enrollment: 489
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: Bipolar disorder is characterized by mood swings that range from high (manic) to low (depressed) states. Sometimes, symptoms of both depression and mania are present (mixed episodes). Asenapine is an investigational medication for the treatment of manic or mixed episodes of bipolar disorder. This is a 3-week study that will test the safety and efficacy of this medication. Participants will receive either asenapine, olanzapine (a medication that is already approved for the treatment of bipolar mania), or placebo (no active medication). Participants will be required to stay in the hospital for at least the first seven days of treatment. Participants who complete the 3 week study may be eligible to continue in extension studies for an additional 9 (study A7501006) to 49 (study A7501007) weeks.


Eligibility criteria: Inclusion Criteria:

* Have a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of bipolar I disorder, current episode manic or mixed.

Exclusion Criteria:

* Participants with unstable medical conditions or clinically significant laboratory abnormalities or participants who are rapid cyclers (i.e., have had 4 or more (including current) mood episodes in the past 12 months); have any other psychiatric disorder other than bipolar I disorder as a primary diagnosis.

Primary outcomes:
measure: Change from Baseline to Day 21 on the Young Mania Rating Scale (YMRS) Total Score
timeFrame: Baseline to Day 21
Secondary outcomes:
measure: Change from Baseline to Day 21 in the Clinical Global Impression Scale for use in Bipolar Disorder (CGI-BP) Severity of Mania
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in the Positive and Negative Symptom Scale (PANSS) Total Score
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline to Day 21
measure: Readiness for Discharge Questionnaire (RDQ)
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in Central Nervous System (CNS) Vital Signs
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in Short Form-36 (SF-36) - Physical Component Summary Scores
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in the Severity of Extrapyramidal Symptoms (EPS)
timeFrame: Baseline to Day 21
measure: Concomitant Medication Usage
timeFrame: Up to Day 21
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after last dose (Up to approximately 51 days)
measure: Change from Baseline to Each Time Point in YMRS Total Score
timeFrame: Days 2, 4, 7, 14, and 21
measure: Change from Baseline to Day 21 in the CGI-BP Severity of Depression
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in the CGI-BP Severity of Overall Bipolar Illness
timeFrame: Baseline to Day 21
measure: Change from Baseline to Day 21 in SF-36 - Mental Component Summary Scores
timeFrame: Baseline to Day 21
measure: Treatment Satisfaction Questionnaire for Medicine (TSQM) Overall Impact Domain Score at Day 21
timeFrame: Day 21
measure: Mean Change from Baseline for Vital Signs
timeFrame: Baseline up to Day 21
measure: Change from Baseline to Day 21 in Body Weight
timeFrame: Baseline to Day 21
measure: Summary of Post-Baseline Markedly Abnormal Biochemistry Laboratory Changes/Values
timeFrame: Up to Day 21
measure: Summary of Post-Baseline Markedly Abnormal Endocrinology/Miscellaneous Laboratory Changes/Values
timeFrame: Up to Day 21
measure: Summary of Post-Baseline Markedly Abnormal Metabolic Chemistry Laboratory Changes/Values
timeFrame: Up to Day 21
measure: Summary of Post-Baseline Markedly Abnormal Hematology Laboratory Values
timeFrame: Up to Day 21
measure: Pharmacokinetics - Plasma asenapine concentrations
timeFrame: Day 1 (pre-dose), 7, 14 and 21 (or endpoint)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Suppes T, Eberhard J, Lemming O, Young AH, McIntyre RS. Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials. Int J Bipolar Disord. 2017 Nov 6;5(1):36. doi: 10.1186/s40345-017-0103-7.
citation: Michalak EE, Guiraud-Diawara A, Sapin C. Asenapine treatment and health-related quality of life in patients experiencing bipolar I disorder with mixed episodes: post-hoc analyses of pivotal trials. Curr Med Res Opin. 2014 Apr;30(4):711-8. doi: 10.1185/03007995.2013.874988. Epub 2014 Jan 10.
citation: Szegedi A, Zhao J, McIntyre RS. Early improvement as a predictor of acute treatment outcome in manic or mixed episodes in bipolar-1 disorder: a pooled, post hoc analysis from the asenapine development program. J Affect Disord. 2013 Sep 25;150(3):745-52. doi: 10.1016/j.jad.2013.01.024. Epub 2013 Mar 6.