Trial Outcomes & Findings for Study of the Efficacy of a Fixed-dose Regimen of Cariprazine Compared to Placebo for Treatment of the Depressive Episode in Participants With Bipolar I Disorder (NCT NCT02670538)

Last Updated: 2019-03-12

Results Overview

MADRS is a 10-item, clinician-rated scale that evaluates the participants 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. Mixed-effects Model for Repeated Measures (MMRM) with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

493 participants

Primary outcome timeframe

Baseline (Week 0) to Week 6

Results posted on

2019-03-12

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Overall Study STARTED	167	168	158
Overall Study Safety Population : Received Study Drug	165	167	158
Overall Study Intent-to-Treat Population	163	162	153
Overall Study COMPLETED	135	136	128
Overall Study NOT COMPLETED	32	32	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Overall Study Withdrawal of Consent	8	6	5
Overall Study Lost to Follow-up	8	12	7
Overall Study Adverse Event	5	5	11
Overall Study Lack of Efficacy	7	1	2
Overall Study Protocol Violation	3	4	1
Overall Study Noncompliance with Study Drug	1	3	2
Overall Study Other Miscellaneous Reasons	0	1	2

Baseline Characteristics

Intent-to-Treat (ITT) Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=167 Participants Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=168 Participants Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=158 Participants Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.	Total n=493 Participants Total of all reporting groups
Age, Continuous	44.4 years STANDARD_DEVIATION 11.6 • n=167 Participants	42.2 years STANDARD_DEVIATION 12.0 • n=168 Participants	43.9 years STANDARD_DEVIATION 11.8 • n=158 Participants	43.5 years STANDARD_DEVIATION 11.8 • n=493 Participants
Sex: Female, Male Female	99 Participants n=167 Participants	107 Participants n=168 Participants	103 Participants n=158 Participants	309 Participants n=493 Participants
Sex: Female, Male Male	68 Participants n=167 Participants	61 Participants n=168 Participants	55 Participants n=158 Participants	184 Participants n=493 Participants
Race/Ethnicity, Customized White	121 Participants n=167 Participants	121 Participants n=168 Participants	117 Participants n=158 Participants	359 Participants n=493 Participants
Race/Ethnicity, Customized Black or African American	46 Participants n=167 Participants	41 Participants n=168 Participants	39 Participants n=158 Participants	126 Participants n=493 Participants
Race/Ethnicity, Customized Asian	0 Participants n=167 Participants	3 Participants n=168 Participants	2 Participants n=158 Participants	5 Participants n=493 Participants
Race/Ethnicity, Customized Multiple Races	0 Participants n=167 Participants	3 Participants n=168 Participants	0 Participants n=158 Participants	3 Participants n=493 Participants
Race/Ethnicity, Customized Hispanic or Latino	18 Participants n=167 Participants	22 Participants n=168 Participants	15 Participants n=158 Participants	55 Participants n=493 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	149 Participants n=167 Participants	146 Participants n=168 Participants	143 Participants n=158 Participants	438 Participants n=493 Participants
Montgomery-Åsberg Depression Rating Scale (MADRS)	31.4 score on a scale STANDARD_DEVIATION 4.5 • n=163 Participants • Intent-to-Treat (ITT) Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.	31.5 score on a scale STANDARD_DEVIATION 4.3 • n=162 Participants • Intent-to-Treat (ITT) Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.	31.5 score on a scale STANDARD_DEVIATION 4.8 • n=153 Participants • Intent-to-Treat (ITT) Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.	31.5 score on a scale STANDARD_DEVIATION 4.5 • n=478 Participants • Intent-to-Treat (ITT) Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.

PRIMARY outcome

Timeframe: Baseline (Week 0) to Week 6

Population: ITT Population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=162 Participants Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=153 Participants Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)	-12.4 score on a scale Standard Error 0.75	-14.8 score on a scale Standard Error 0.76	-14.1 score on a scale Standard Error 0.78

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 6

Population: ITT population consisted of all participants in Safety Population who had at least 1 postbaseline assessment of MADRS total score.

CGI-S is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of other patients 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 patients". A negative change from Baseline indicates improvement. MMRM with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).

Outcome measures

Outcome measures
Measure	Placebo n=163 Participants Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=162 Participants Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=153 Participants Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to 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	-1.2 score on a scale Standard Error 0.09	-1.5 score on a scale Standard Error 0.09	-1.4 score on a scale Standard Error 0.09

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 36 other events

Deaths: 0 deaths

Cariprazine 1.5 mg

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Cariprazine 3.0 mg

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=165 participants at risk Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=167 participants at risk Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=158 participants at risk Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
General disorders Non-cardiac chest pain	0.61% 1/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.61% 1/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Pregnancy, puerperium and perinatal conditions Abortion	0.00% 0/97 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/107 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.97% 1/103 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Bipolar disorder	0.61% 1/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Depression	0.00% 0/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.60% 1/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Mania	0.61% 1/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Substance abuse	0.61% 1/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	0.00% 0/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.

Other adverse events

Other adverse events
Measure	Placebo n=165 participants at risk Following a 7 to 14 day screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.	Cariprazine 1.5 mg n=167 participants at risk Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.	Cariprazine 3.0 mg n=158 participants at risk Following a 7 to 14 day screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
Nervous system disorders Headache	8.5% 14/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	8.4% 14/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	8.9% 14/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Insomnia	4.2% 7/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	4.8% 8/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	7.0% 11/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Gastrointestinal disorders Nausea	3.0% 5/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	7.8% 13/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	5.1% 8/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
General disorders Fatigue	1.2% 2/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	5.4% 9/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	3.2% 5/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Nervous system disorders Akathisia	1.8% 3/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	5.4% 9/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	9.5% 15/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Restlessness	3.0% 5/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	2.4% 4/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	7.0% 11/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.
Psychiatric disorders Agitation	6.1% 10/165 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	1.8% 3/167 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.	4.4% 7/158 • First dose of study drug up to Day 50 Safety Population, all participants in the Randomized Population who took at least 1 dose of double-blind investigational product, was used to determine the number of participants at risk for Serious Adverse Events and Other Adverse Events.

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