Trial Outcomes & Findings for Study Evaluating Cariprazine (RGH-188) in the Treatment of Patients With Acute Mania (NCT NCT00488618)

Last Updated: 2017-04-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

238 participants

Primary outcome timeframe

Baseline, Week 3

Results posted on

2017-04-14

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Overall Study STARTED	120	118
Overall Study Safety Population: Received Study Drug	118	118
Overall Study COMPLETED	73	75
Overall Study NOT COMPLETED	47	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Overall Study Adverse Event	13	17
Overall Study Insufficient Therapeutic Response	18	11
Overall Study Protocol Violation	0	2
Overall Study Withdrawal of Consent	15	13
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=118 Participants Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine n=118 Participants Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.	Total n=236 Participants Total of all reporting groups
Age, Continuous	38.7 years STANDARD_DEVIATION 11.0 • n=5 Participants	38.0 years STANDARD_DEVIATION 10.3 • n=7 Participants	38.3 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	38 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	80 Participants n=7 Participants	157 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	114 Participants n=5 Participants	112 Participants n=7 Participants	226 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	55 Participants n=5 Participants	47 Participants n=7 Participants	102 Participants n=5 Participants
Race/Ethnicity, Customized Black	31 Participants n=5 Participants	36 Participants n=7 Participants	67 Participants n=5 Participants
Race/Ethnicity, Customized Asian	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Weight	79.3 kilogram (kg) STANDARD_DEVIATION 20.0 • n=5 Participants	75.0 kilogram (kg) STANDARD_DEVIATION 20.3 • n=7 Participants	77.2 kilogram (kg) STANDARD_DEVIATION 20.2 • n=5 Participants
Height	170.0 centimeter (cm) STANDARD_DEVIATION 10.4 • n=5 Participants	169.9 centimeter (cm) STANDARD_DEVIATION 10.0 • n=7 Participants	170.0 centimeter (cm) STANDARD_DEVIATION 10.2 • n=5 Participants
Body Mass Index (BMI)	27.2 kg/meter(m)^2 STANDARD_DEVIATION 5.8 • n=5 Participants	25.8 kg/meter(m)^2 STANDARD_DEVIATION 5.9 • n=7 Participants	26.5 kg/meter(m)^2 STANDARD_DEVIATION 5.9 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: 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).

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine n=118 Participants Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3	-8.91 score on a scale Standard Error 1.083	-15.02 score on a scale Standard Error 1.078

SECONDARY outcome

Timeframe: Baseline, 3 Weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=117 Participants Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine n=118 Participants Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3	-0.93 score on a scale Standard Error 0.125	-1.57 score on a scale Standard Error 0.125

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 73 other events

Deaths: 0 deaths

Cariprazine

Serious events: 7 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=118 participants at risk Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine n=118 participants at risk Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Psychiatric disorders Mania	4.2% 5/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	3.4% 4/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Convulsion	0.00% 0/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Extrapyramidal disorder	0.00% 0/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Delusion	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	0.00% 0/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	0.00% 0/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Therapeutic Area Head

Allergan, Inc.

Phone: 714-246-4500

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=118 participants at risk Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.	Cariprazine n=118 participants at risk Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Eye disorders Vision blurred	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	5.9% 7/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	8.5% 10/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	16.1% 19/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	10.2% 12/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	16.1% 19/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	7.6% 9/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	12.7% 15/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	8.5% 10/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	7.6% 9/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	6.8% 8/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Toothache	6.8% 8/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	2.5% 3/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	5.9% 7/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	6.8% 8/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Investigations Blood creatine phosphokinase increased	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	4.2% 5/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	3.4% 4/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Extrapyramidal disorder	11.0% 13/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	24.6% 29/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	22.0% 26/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	20.3% 24/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Akathisia	6.8% 8/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	19.5% 23/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	6.8% 8/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	10.2% 12/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Sedation	1.7% 2/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	5.9% 7/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Nervous system disorders Tremor	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	2.5% 3/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	8.5% 10/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Restlessness	0.85% 1/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	6.8% 8/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.
Psychiatric disorders Agitation	8.5% 10/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.	5.1% 6/118 • First dose of study drug to 30 days past last dose (Up to 51 days) Safety Population included all participants who received at least 1 dose of study drug.