40 Week Trial to Study the Safety of Asenapine When Added to Lithium or Valproate in the Treatment of Bipolar Disorder (A7501009)(P05786)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00145509
• Collaborator: (none)
• Enrollment: 77
• Arms: 2
• Duration (Months): 28

Study Details

Study Description

Brief Summary

The primary objective of this trial was to characterize the long-term (up to 40 weeks) safety and tolerability of asenapine in bipolar I disorder subjects who had not completely responded to continuing treatment with lithium or valproic acid (VPA) for the treatment of an acute manic or mixed episodes upon enrollment into the 12-week lead-in trial, A7501008 (NCT00145470). The safety comparison was between the group receiving lithium or VPA and placebo against the group receiving lithium or VPA and asenapine, with the caveat that all subjects may have received benzodiazepine and/or antidepressant rescue medication as needed.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Asenapine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Placebo-Controlled, Double-Blinded Continuation Trial Evaluating the Safety and Efficacy of Asenapine in Subjects Completing a 12-week Lead-in Trial and Continuing Lithium or Valproic Acid/Divalproex Sodium for the Treatment of an Acute Manic or Mixed Episode
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Asenapine Asenapine	Drug: Asenapine; Asenapine 5 or 10 mg twice daily (BID) sublingually for 40 weeks; Other Names: Org 5222
Placebo Comparator: Placebo Placebo	Drug: Placebo; Fast-dissolving tablet; twice daily (BID) sublingually for 40 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced an Adverse Event [up to 52 weeks]

   Participants who experienced treatment-emergent adverse events, defined as adverse events reported on or after the first dose of study medication in the 12-week lead-in study through the last dose of study drug + 7 days (or + 30 days for serious adverse events).

2. Number of Participants Who Discontinued Because of an Adverse Event [40 weeks]

   Participants who discontinued study medication due to adverse events.

3. Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score [Baseline and 52 Weeks]

   The Y-MRS is an 11-item, clinician-rated instrument used for assessing the symptoms of mania. Y-MRS total score range = 0-60; higher scores indicate greater severity of symptoms.

4. Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score [Baseline and 52 Weeks]

   The MADRS is a 10-item clinician-rated scale for assessing the severity of symptoms of depression. MADRS total score range = 0-60; higher scores indicate greater severity of symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have bipolar I disorder (current episode manic or mixed), be treated with lithium or valproic acid, and have completed the a 12-week lead-in trial

Exclusion Criteria:

• Have an unstable medical condition or clinically significant laboratory abnormality.

• Have a primary diagnosis other than bipolar I disorder.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00145509
• Other Study ID Numbers: P05786; A7501009
• First Posted: Sep 5, 2005
• Last Update Posted: Feb 8, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Bipolar Disorder; Asenapine

Study Results

Participant Flow

Arm/Group Title	Asenapine	Placebo
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)	Placebo sublingually BID
Period Title: Overall Study
STARTED	41	36
COMPLETED	19	15
NOT COMPLETED	22	21

Baseline Characteristics

Arm/Group Title	Asenapine	Placebo	Total
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)	Placebo sublingually BID	Total of all reporting groups
Overall Participants	41	36	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.0 (11.79)	38.7 (13.42)	38.9 (12.49)
Sex: Female, Male (Count of Participants)
Female	16 39%	18 50%	34 44.2%
Male	25 61%	18 50%	43 55.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced an Adverse Event
Description	Participants who experienced treatment-emergent adverse events, defined as adverse events reported on or after the first dose of study medication in the 12-week lead-in study through the last dose of study drug + 7 days (or + 30 days for serious adverse events).
Time Frame	up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Asenapine	Placebo
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)	Placebo sublingually BID
Measure Participants	41	36
Number [Participants]	32 78%	25 69.4%

2. Primary Outcome

Title	Number of Participants Who Discontinued Because of an Adverse Event
Description	Participants who discontinued study medication due to adverse events.
Time Frame	40 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Asenapine	Placebo
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)	Placebo sublingually BID
Measure Participants	41	36
Number [participants]	10 24.4%	3 8.3%

3. Primary Outcome

Title	Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score
Description	The Y-MRS is an 11-item, clinician-rated instrument used for assessing the symptoms of mania. Y-MRS total score range = 0-60; higher scores indicate greater severity of symptoms.
Time Frame	Baseline and 52 Weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat are subjects who took at least one dose of double-blind study medication in the extension study and had at least one Y-MRS and MADRS assessment during the extension study.

Arm/Group Title	Asenapine	Placebo
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)	Placebo sublingually BID
Measure Participants	38	33
Mean (Standard Deviation) [Score on a Scale]	-17.2 (13.65)	-19.7 (11.81)

4. Primary Outcome

Title	Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score
Description	The MADRS is a 10-item clinician-rated scale for assessing the severity of symptoms of depression. MADRS total score range = 0-60; higher scores indicate greater severity of symptoms.
Time Frame	Baseline and 52 Weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat are subjects who took at least one dose of double-blind study medication in the extension study and had at least one Y-MRS and MADRS assessment during the extension study.

Arm/Group Title	Asenapine	Placebo
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)	Placebo sublingually BID
Measure Participants	38	33
Mean (Standard Deviation) [Score on a scale]	-3.3 (9.75)	-3.9 (7.71)

Adverse Events

Arm/Group Title	Asenapine		Placebo
Arm/Group Description	Asenapine 5 or 10 mg sublingually twice daily (BID)		Placebo sublingually BID
All Cause Mortality
	Asenapine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asenapine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/41 (22%)		4/36 (11.1%)
Injury, poisoning and procedural complications
INTENTIONAL OVERDOSE	1/41 (2.4%)	1	0/36 (0%)	0
Nervous system disorders
EXTRAPYRAMIDAL DISORDER	1/41 (2.4%)	1	0/36 (0%)	0
Psychiatric disorders
BIPOLAR I DISORDER	0/41 (0%)	0	1/36 (2.8%)	3
DEPRESSION	1/41 (2.4%)	1	0/36 (0%)	0
DEPRESSIVE SYMPTOM	1/41 (2.4%)	1	0/36 (0%)	0
MANIA	4/41 (9.8%)	4	4/36 (11.1%)	4
SUICIDAL IDEATION	1/41 (2.4%)	1	0/36 (0%)	0
SUICIDE ATTEMPT	2/41 (4.9%)	3	0/36 (0%)	0
Other (Not Including Serious) Adverse Events
	Asenapine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/41 (61%)		18/36 (50%)
Gastrointestinal disorders
CONSTIPATION	4/41 (9.8%)	8	1/36 (2.8%)	1
DIARRHOEA	2/41 (4.9%)	2	5/36 (13.9%)	5
DRY MOUTH	3/41 (7.3%)	3	3/36 (8.3%)	3
HYPOAESTHESIA ORAL	3/41 (7.3%)	3	1/36 (2.8%)	1
NAUSEA	3/41 (7.3%)	4	2/36 (5.6%)	2
VOMITING	4/41 (9.8%)	4	2/36 (5.6%)	3
General disorders
IRRITABILITY	3/41 (7.3%)	3	1/36 (2.8%)	1
PYREXIA	0/41 (0%)	0	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
BACK PAIN	1/41 (2.4%)	1	3/36 (8.3%)	3
MYALGIA	2/41 (4.9%)	5	2/36 (5.6%)	2
Nervous system disorders
DIZZINESS	2/41 (4.9%)	2	2/36 (5.6%)	3
DYSKINESIA	3/41 (7.3%)	4	0/36 (0%)	0
HEADACHE	8/41 (19.5%)	11	6/36 (16.7%)	7
PARKINSONISM	1/41 (2.4%)	2	2/36 (5.6%)	3
SEDATION	6/41 (14.6%)	8	2/36 (5.6%)	2
SOMNOLENCE	6/41 (14.6%)	7	3/36 (8.3%)	4
TREMOR	3/41 (7.3%)	5	3/36 (8.3%)	3
Psychiatric disorders
ANXIETY	4/41 (9.8%)	4	4/36 (11.1%)	11
DEPRESSION	1/41 (2.4%)	1	2/36 (5.6%)	3
INSOMNIA	8/41 (19.5%)	10	5/36 (13.9%)	8
Respiratory, thoracic and mediastinal disorders
COUGH	1/41 (2.4%)	1	3/36 (8.3%)	3
PHARYNGOLARYNGEAL PAIN	2/41 (4.9%)	2	3/36 (8.3%)	3
Skin and subcutaneous tissue disorders
RASH	2/41 (4.9%)	3	2/36 (5.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institution will provide manuscripts, abstracts, or the full text of any other intended disclosure to the sponsor at least 30 days prior to submission for publication or other disclosure. If any patent action is required to protect intellectual property rights, Institution agrees to delay the disclosure for a period not to exceed and additional 60 days. Institution will, on request, remove any previously undisclosed Confidential Information (other than study results) before disclosure.