Trial Outcomes & Findings for Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression (NCT NCT02670551)

Last Updated: 2019-01-30

Results Overview

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

488 participants

Primary outcome timeframe

Baseline (Week 0) to Week 6

Results posted on

2019-01-30

Participant Flow

Total 782 participants were screened for eligibility; 488 participants randomized to receive double-blind treatment; 480 participants received at least 1 dose of double-blind treatment (Safety Population) and 474 participants had at least 1 postbaseline Montgomery-Åsberg Depression Rating Scale total score assessment (Intent-to-Treat Population).

Participant milestones

Participant milestones
Measure	Placebo Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Overall Study STARTED	163	160	165
Overall Study Received Treatment (Safety Population)	158	157	165
Overall Study COMPLETED	135	134	134
Overall Study NOT COMPLETED	28	26	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Overall Study Adverse Event	4	7	9
Overall Study Lack of Efficacy	2	0	3
Overall Study Withdrawal of Consent	6	3	8
Overall Study Lost to Follow-up	5	7	6
Overall Study Protocol Violation	1	0	0
Overall Study Noncompliance with study drug	3	3	2
Overall Study Other Miscellaneous Reasons	2	3	3
Overall Study Did Not Receive Treatment	5	3	0

Baseline Characteristics

Montgomery-Åsberg Depression Rating Scale (MADRS) score at Baseline was analyzed for ITT population.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=163 Participants Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=160 Participants Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=165 Participants Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.	Total n=488 Participants Total of all reporting groups
Age, Continuous	43.9 years n=163 Participants	42.6 years n=160 Participants	41.9 years n=165 Participants	42.8 years n=488 Participants
Sex: Female, Male Female	94 Participants n=163 Participants	101 Participants n=160 Participants	94 Participants n=165 Participants	289 Participants n=488 Participants
Sex: Female, Male Male	69 Participants n=163 Participants	59 Participants n=160 Participants	71 Participants n=165 Participants	199 Participants n=488 Participants
Race/Ethnicity, Customized White	118 Participants n=163 Participants	126 Participants n=160 Participants	126 Participants n=165 Participants	370 Participants n=488 Participants
Race/Ethnicity, Customized Black or African American	39 Participants n=163 Participants	29 Participants n=160 Participants	37 Participants n=165 Participants	105 Participants n=488 Participants
Race/Ethnicity, Customized Asian	3 Participants n=163 Participants	2 Participants n=160 Participants	0 Participants n=165 Participants	5 Participants n=488 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=163 Participants	1 Participants n=160 Participants	1 Participants n=165 Participants	3 Participants n=488 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=165 Participants	2 Participants n=488 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=163 Participants	2 Participants n=160 Participants	1 Participants n=165 Participants	3 Participants n=488 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants n=163 Participants	15 Participants n=160 Participants	14 Participants n=165 Participants	42 Participants n=488 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	150 Participants n=163 Participants	145 Participants n=160 Participants	151 Participants n=165 Participants	446 Participants n=488 Participants
Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline	30.3 score on a scale STANDARD_DEVIATION 4.5 • n=156 Participants • Montgomery-Åsberg Depression Rating Scale (MADRS) score at Baseline was analyzed for ITT population.	30.6 score on a scale STANDARD_DEVIATION 4.2 • n=154 Participants • Montgomery-Åsberg Depression Rating Scale (MADRS) score at Baseline was analyzed for ITT population.	31.1 score on a scale STANDARD_DEVIATION 4.8 • n=164 Participants • Montgomery-Åsberg Depression Rating Scale (MADRS) score at Baseline was analyzed for ITT population.	30.7 score on a scale STANDARD_DEVIATION 4.5 • n=474 Participants • Montgomery-Åsberg Depression Rating Scale (MADRS) score at Baseline was analyzed for ITT population.
Clinical Global Impressions-Severity (CGI-S) Score at Baseline	4.5 score on a scale STANDARD_DEVIATION 0.5 • n=156 Participants • Clinical Global Impressions-Severity (CGI-S) score at Baseline was analyzed for ITT population.	4.5 score on a scale STANDARD_DEVIATION 0.5 • n=154 Participants • Clinical Global Impressions-Severity (CGI-S) score at Baseline was analyzed for ITT population.	4.5 score on a scale STANDARD_DEVIATION 0.5 • n=164 Participants • Clinical Global Impressions-Severity (CGI-S) score at Baseline was analyzed for ITT population.	4.5 score on a scale STANDARD_DEVIATION 0.5 • n=474 Participants • Clinical Global Impressions-Severity (CGI-S) score at Baseline was analyzed for ITT population.

PRIMARY outcome

Timeframe: Baseline (Week 0) to Week 6

Population: The Intent-to-Treat (ITT) Population included all participants from the safety population who had at least 1 postbaseline assessment of the MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Outcome measures
Measure	Placebo n=137 Participants Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=135 Participants Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=136 Participants Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Week 6	-12.6 score on a scale Standard Error 0.76	-15.1 score on a scale Standard Error 0.77	-15.6 score on a scale Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 6

Population: ITT Population included all participants from the safety population who had at least 1 postbaseline assessment of the MADRS total score. Overall number of participants analyzed is the number of participants with data available for analysis at the given time-point.

The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other participants the physician has observed. The participant was rated on a scale from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill participants." A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=137 Participants Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=135 Participants Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=136 Participants Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 6	-1.3 score on a scale Standard Error 0.09	-1.6 score on a scale Standard Error 0.10	-1.6 score on a scale Standard Error 0.09

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Cariprazine 1.5 mg

Serious events: 2 serious events

Other events: 48 other events

Deaths: 0 deaths

Cariprazine 3.0 mg

Serious events: 2 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=158 participants at risk Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=157 participants at risk Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=165 participants at risk Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.64% 1/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Gastrointestinal disorders Abdominal pain	0.63% 1/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Infections and infestations Chronic tonsillitis	0.63% 1/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Psychiatric disorders Bipolar disorder	0.00% 0/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.61% 1/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Psychiatric disorders Suicidal ideation	0.00% 0/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.61% 1/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.64% 1/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	0.00% 0/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.

Other adverse events

Other adverse events
Measure	Placebo n=158 participants at risk Following a 7 to 14 days screening/washout period, placebo-matching cariprazine capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=157 participants at risk Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligram (mg) capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=165 participants at risk Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day for 2 weeks followed by cariprazine 3.0 mg capsule, one per day, orally beginning on Day 15 for 4 weeks.
Gastrointestinal disorders Nausea	0.63% 1/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	3.8% 6/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	9.1% 15/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Gastrointestinal disorders Dry mouth	5.7% 9/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	3.8% 6/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	1.8% 3/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Nervous system disorders Headache	8.2% 13/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	4.5% 7/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	7.3% 12/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Nervous system disorders Akathisia	3.2% 5/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	6.4% 10/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	5.5% 9/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Nervous system disorders Dizziness	1.9% 3/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	5.1% 8/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	3.6% 6/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Nervous system disorders Somnolence	1.9% 3/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	5.1% 8/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	3.6% 6/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Nervous system disorders Sedation	1.3% 2/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	5.1% 8/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	3.0% 5/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Psychiatric disorders Insomnia	7.0% 11/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	4.5% 7/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	7.3% 12/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.
Psychiatric disorders Restlessness	3.8% 6/158 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	1.3% 2/157 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.	7.3% 12/165 • First dose to 30 days past last dose (Up to 80 Days) Safety Population included all participants in the randomized population who took at least 1 dose of double-blind investigational product.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER