Study Evaluating Cariprazine (RGH-188) in the Treatment of Patients With Acute Mania

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00488618
• Collaborator: Gedeon Richter Ltd. (Industry)
• Enrollment: 238
• Location: 1
• Arms: 2
• Duration (Months): 13
• Patients Per Site Per Month: 18.3

Study Details

Study Description

Brief Summary

This is a study designed to evaluate the efficacy, safety, and tolerability of RGH-188 monotherapy in the treatment of acute mania. This study will be 5 weeks in duration; 3 weeks double-blind treatment and 2-weeks safety follow-up. All patients meeting the eligibility criteria will be randomized to one of two treatment groups: RGH-188 or placebo

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Cariprazine (RGH-188); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 238 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of RGH-188 in Patients With Acute Mania Associated With Bipolar I Disorder
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cariprazine Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.	Drug: Cariprazine (RGH-188); Cariprazine 3 mg - 12 mg oral administration, once per day.
Placebo Comparator: Placebo Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Drug: Placebo; Dose-matched placebo oral administration, once per day.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3 [Baseline, Week 3]

   The YMRS is an 11-item scale that assesses manic symptoms based on the participant's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11-items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of the abnormality for 7-items are rated on a five-point scale (0-4) and 4-items on a nine-point scale (0-8). The individual scores are summed for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Analyses are based on an Analysis of Covariance (ANCOVA) model for change from Baseline with treatment group and study center as factors and Baseline value as covariate.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3 [Baseline, 3 Weeks]

   The CGI-S measures the investigator's assessment of overall severity of the participant's illness compared with the severity of illness in other patients the physician has observed using a 7-point scale (1=Normal, not ill at all to 7=Among the most extremely ill participants). A negative change from Baseline indicates improvement. Analyses are based on ANCOVA model for change from Baseline with treatment group and study center as factors and Baseline CGI-S score as covariate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female inpatients 18 to 65 years of age

• Meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV) criteria for bipolar I disorder, acute manic or mixed episode

• Having a total Young Mania Rating Scale (YMRS) score >= 20 and a score of at least 4 on two of the following YMRS items:

• Irritability,

• Speech,

• Content, and

• Disruptive/Aggressive Behavior

Exclusion Criteria:

• Patients who exhibit abnormalities on physical examination, have abnormal vital-signs, electrocardiogram (ECG), or clinical laboratory values [such as thyroid-stimulating hormone (TSH)].

• Patients with Montgomery-Åsberg Depression Rating Scale (MADRS) total score >= 18 at Visit 2.

• Patients experiencing first manic episode.

• Patients that have received electroconvulsive therapy (ECT) or a depot neuroleptic in the 3 months prior to Visit 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For information regarding investigative sites, contact Forest Professional Affairs	St. Louis	Missouri	United States	63045

Sponsors and Collaborators

• Forest Laboratories
• Gedeon Richter Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00488618
• Other Study ID Numbers: RGH-MD-31
• First Posted: Jun 20, 2007
• Last Update Posted: Apr 14, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Forest Laboratories: Mania; Bipolar I Disorder; Acute Mania Associated with Bipolar I Disorder
• Additional relevant MeSH terms: Mania; Bipolar Disorder; Cariprazine

Study Results

Participant Flow

Arm/Group Title	Placebo	Cariprazine
Arm/Group Description	Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Period Title: Overall Study
STARTED	120	118
Safety Population: Received Study Drug	118	118
COMPLETED	73	75
NOT COMPLETED	47	43

Baseline Characteristics

Arm/Group Title	Placebo	Cariprazine	Total
Arm/Group Description	Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.	Total of all reporting groups
Overall Participants	118	118	236
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.7 (11.0)	38.0 (10.3)	38.3 (10.7)
Sex: Female, Male (Count of Participants)
Female	41 34.7%	38 32.2%	79 33.5%
Male	77 65.3%	80 67.8%	157 66.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 3.4%	6 5.1%	10 4.2%
Not Hispanic or Latino	114 96.6%	112 94.9%	226 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	55 46.6%	47 39.8%	102 43.2%
Black	31 26.3%	36 30.5%	67 28.4%
Asian	28 23.7%	30 25.4%	58 24.6%
Other	4 3.4%	5 4.2%	9 3.8%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	79.3 (20.0)	75.0 (20.3)	77.2 (20.2)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	170.0 (10.4)	169.9 (10.0)	170.0 (10.2)
Body Mass Index (BMI) (kg/meter(m)^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/meter(m)^2]	27.2 (5.8)	25.8 (5.9)	26.5 (5.9)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3
Description	The YMRS is an 11-item scale that assesses manic symptoms based on the participant's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11-items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of the abnormality for 7-items are rated on a five-point scale (0-4) and 4-items on a nine-point scale (0-8). The individual scores are summed for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Analyses are based on an Analysis of Covariance (ANCOVA) model for change from Baseline with treatment group and study center as factors and Baseline value as covariate.
Time Frame	Baseline, Week 3

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included Participants who received at least 1 dose of study drug and who had at least 1 post-baseline YMRS assessment, last observation carried forward (LOCF).

Arm/Group Title	Placebo	Cariprazine
Arm/Group Description	Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Measure Participants	117	118
Least Squares Mean (Standard Error) [score on a scale]	-8.91 (1.083)	-15.02 (1.078)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -8.9 to -3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	cariprazine - placebo

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3
Description	The CGI-S measures the investigator's assessment of overall severity of the participant's illness compared with the severity of illness in other patients the physician has observed using a 7-point scale (1=Normal, not ill at all to 7=Among the most extremely ill participants). A negative change from Baseline indicates improvement. Analyses are based on ANCOVA model for change from Baseline with treatment group and study center as factors and Baseline CGI-S score as covariate.
Time Frame	Baseline, 3 Weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population included all participants who received at least 1 dose of study drug and who had at least 1 post-baseline YMRS assessment, LOCF.

Arm/Group Title	Placebo	Cariprazine
Arm/Group Description	Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Measure Participants	117	118
Least Squares Mean (Standard Error) [score on a scale]	-0.93 (0.125)	-1.57 (0.125)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Cariprazine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95%; -0.97 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	cariprazine - placebo

Adverse Events

Time Frame	First dose of study drug to 30 days past last dose (Up to 51 days)
Adverse Event Reporting Description	Safety Population included all participants who received at least 1 dose of study drug.
Arm/Group Title	Placebo		Cariprazine
Arm/Group Description	Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.		Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
All Cause Mortality
	Placebo		Cariprazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Cariprazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/118 (5.1%)		7/118 (5.9%)
Nervous system disorders
Convulsion	0/118 (0%)		1/118 (0.8%)
Extrapyramidal disorder	0/118 (0%)		1/118 (0.8%)
Psychiatric disorders
Mania	5/118 (4.2%)		4/118 (3.4%)
Delusion	1/118 (0.8%)		0/118 (0%)
Vascular disorders
Hypertension	1/118 (0.8%)		0/118 (0%)
Deep vein thrombosis	0/118 (0%)		1/118 (0.8%)
Other (Not Including Serious) Adverse Events
	Placebo		Cariprazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/118 (61.9%)		90/118 (76.3%)
Eye disorders
Vision blurred	1/118 (0.8%)		7/118 (5.9%)
Gastrointestinal disorders
Constipation	10/118 (8.5%)		19/118 (16.1%)
Nausea	12/118 (10.2%)		19/118 (16.1%)
Dyspepsia	9/118 (7.6%)		15/118 (12.7%)
Vomiting	6/118 (5.1%)		10/118 (8.5%)
Diarrhoea	9/118 (7.6%)		8/118 (6.8%)
Toothache	8/118 (6.8%)		3/118 (2.5%)
General disorders
Pyrexia	7/118 (5.9%)		8/118 (6.8%)
Investigations
Blood creatine phosphokinase increased	6/118 (5.1%)		5/118 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/118 (0.8%)		6/118 (5.1%)
Pain in extremity	4/118 (3.4%)		6/118 (5.1%)
Nervous system disorders
Extrapyramidal disorder	13/118 (11%)		29/118 (24.6%)
Headache	26/118 (22%)		24/118 (20.3%)
Akathisia	8/118 (6.8%)		23/118 (19.5%)
Dizziness	8/118 (6.8%)		12/118 (10.2%)
Sedation	2/118 (1.7%)		7/118 (5.9%)
Tremor	6/118 (5.1%)		6/118 (5.1%)
Psychiatric disorders
Insomnia	3/118 (2.5%)		10/118 (8.5%)
Restlessness	1/118 (0.8%)		8/118 (6.8%)
Agitation	10/118 (8.5%)		6/118 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.