Trial Outcomes & Findings for Long-term Safety and Tolerability of Cariprazine for Bipolar I Disorder (NCT NCT01059539)

Last Updated: 2019-06-13

Results Overview

The Young Mania Rating Scale (YMRS) is an 11-item scale that assesses manic symptoms based on the patient'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 each item is rated on a 5-point (0-4) or a 9-point (0-8) scale. The total score of all 11 items can range from 0 to 60. A higher score indicates worse manic symptoms. A negative change score indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

403 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2019-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Cariprazine 3-12 mg/Day for 16 Weeks Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Overall Study STARTED	403
Overall Study COMPLETED	132
Overall Study NOT COMPLETED	271

Reasons for withdrawal

Reasons for withdrawal
Measure	Cariprazine 3-12 mg/Day for 16 Weeks Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Overall Study Adverse Event	66
Overall Study Insufficient Therapeutic Response	26
Overall Study Protocol Violation	55
Overall Study Withdrawal of Consent	80
Overall Study Lost to Follow-up	42
Overall Study Reason Not Specified	2

Baseline Characteristics

Long-term Safety and Tolerability of Cariprazine for Bipolar I Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cariprazine 3-12 mg/Day for 16 Weeks n=402 Participants Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Age, Continuous	41.4 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	172 Participants n=5 Participants
Sex: Female, Male Male	230 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	370 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	182 Participants n=5 Participants
Race (NIH/OMB) White	206 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Weight	86.52 kg STANDARD_DEVIATION 17.83 • n=5 Participants
Body Mass Index (BMI)	29.21 kg/m^2 STANDARD_DEVIATION 5.34 • n=5 Participants
Waist circumference	97.86 cm STANDARD_DEVIATION 14.05 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: Intent-to-treat population: All enrolled participants who took at least 1 dose of investigational product and who had a Baseline and at least 1 post-baseline assessment of the Young Mania Rating Scale.

Outcome measures

Outcome measures
Measure	Cariprazine 3-12 mg/Day for 16 Weeks n=399 Participants Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Change From Baseline in the YMRS Total Score at Week 16	-15.2 Units on a scale Standard Deviation 9.2

SECONDARY outcome

Timeframe: Baseline to Week 16

The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated scale that evaluates the patient's depressive symptomatology during the previous week. Patients are rated on 10 items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point (0-6) scale. The total score can range from 0 to 42. A higher score indicates greater depressive symptomatology. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Cariprazine 3-12 mg/Day for 16 Weeks n=399 Participants Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Change From Baseline in the MADRS Total Score at Week 16	-1.6 Units on a scale Standard Deviation 7.5

Adverse Events

Cariprazine 3-12 mg/Day for 16 Weeks

Serious events: 34 serious events

Other events: 293 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cariprazine 3-12 mg/Day for 16 Weeks n=402 participants at risk Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Psychiatric disorders Mania	2.2% 9/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Depression	1.2% 5/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Akathisia	0.75% 3/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Suicidal ideation	0.50% 2/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Suicide attempt	0.50% 2/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Cardiac disorders Angina pectoris	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Anxiety	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Respiratory, thoracic and mediastinal disorders Asthma	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Bipolar I disorder	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Cardiac disorders Bradycardia	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Dermal cyst	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Immune system disorders Hypersensitivity	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Insomnia	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Injury, poisoning and procedural complications Intentional overdose	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Respiratory, thoracic and mediastinal disorders Non-cardiac chest pain	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Panic attack	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Paranoia	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Infections and infestations Pneumonia	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Social circumstances Social stay hospitalization	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Nervous system disorders Tremor	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Gastrointestinal disorders Large intestinal obstruction/Large bowel obstruction	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Psychotic disorder/Increased psychosis	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Psychotic disorder/Psychosis	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Mania/Increased mania	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Mania/Worsening of mania	0.25% 1/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.

Other adverse events

Other adverse events
Measure	Cariprazine 3-12 mg/Day for 16 Weeks n=402 participants at risk Participants received cariprazine 1.5 mg orally on Day 1 and cariprazine 3.0 mg orally on Days 2 and 3. Starting on Day 4, the dose could be increased in increments of 3 mg every 2 days up to a maximum dose of 12 mg, if the response was not adequate and there were no tolerability issues based on the judgment of the principal investigator.
Gastrointestinal disorders Constipation	10.9% 44/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Gastrointestinal disorders Diarrhoea	5.5% 22/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Gastrointestinal disorders Dyspepsia	9.5% 38/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Gastrointestinal disorders Nausea	10.4% 42/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Gastrointestinal disorders Toothache	8.7% 35/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Gastrointestinal disorders Vomiting	6.2% 25/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Investigations Weight increased	6.2% 25/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Musculoskeletal and connective tissue disorders Back pain	8.0% 32/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Nervous system disorders Akathisia	32.1% 129/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Nervous system disorders Extrapyramidal disorder	7.0% 28/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Nervous system disorders Headache	17.2% 69/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Nervous system disorders Sedation	6.0% 24/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Nervous system disorders Tremor	7.7% 31/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Insomnia	6.7% 27/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.
Psychiatric disorders Restlessness	6.5% 26/402 Safety population: All enrolled participants who took at least 1 dose of investigational product.

Additional Information

Willie R. Earley, MD Associate Vice President Clinical Development-CNS

Allergan

Phone: 714-246-4500

Email: [email protected]

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