Trial Outcomes & Findings for Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD) (NCT NCT01715805)

Last Updated: 2019-08-28

Results Overview

The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Patients are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1022 participants

Primary outcome timeframe

Baseline (Week 8)

Results posted on

2019-08-28

Participant Flow

1022 patients participated in an 8 week open label antidepression therapy (ADT) + single blind placebo lead-in period. 530 patients who did not respond were randomized to receive ADT or cariprazine + ADT in the double-blind period and non-responders continued ADT + Placebo.

Participant milestones

Participant milestones
Measure	Placebo + ADT Lead-in Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.	Placebo + ADT (Double-Blind) Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Cariprazine + ADT (Double-Blind) Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).	Placebo + ADT (Continued Treatment) Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks.
Placebo + ADT Lead-in Period STARTED	1022	0	0	0
Placebo + ADT Lead-in Period COMPLETED	807	0	0	0
Placebo + ADT Lead-in Period NOT COMPLETED	215	0	0	0
Double-Blind or Continued Treatment STARTED	0	261	269	270
Double-Blind or Continued Treatment Double-Blind Safety Population	0	258	269	0
Double-Blind or Continued Treatment COMPLETED	0	222	213	222
Double-Blind or Continued Treatment NOT COMPLETED	0	39	56	48

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + ADT Lead-in Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.	Placebo + ADT (Double-Blind) Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Cariprazine + ADT (Double-Blind) Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).	Placebo + ADT (Continued Treatment) Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks.
Placebo + ADT Lead-in Period Adverse Event	41	0	0	0
Placebo + ADT Lead-in Period Insufficient therapeutic response	6	0	0	0
Placebo + ADT Lead-in Period Protocol Violation	74	0	0	0
Placebo + ADT Lead-in Period Withdrawal of Consent	49	0	0	0
Placebo + ADT Lead-in Period Lost to Follow-up	34	0	0	0
Placebo + ADT Lead-in Period Site Terminated by Sponsor	1	0	0	0
Placebo + ADT Lead-in Period Other Reason Not Specified	10	0	0	0
Double-Blind or Continued Treatment Study or Site Terminated by Sponsor	0	0	0	1
Double-Blind or Continued Treatment Adverse Event	0	3	23	2
Double-Blind or Continued Treatment Protocol Violation	0	14	12	19
Double-Blind or Continued Treatment Withdrawal of consent	0	11	11	13
Double-Blind or Continued Treatment Lost to Follow-up	0	7	10	10
Double-Blind or Continued Treatment Other Reason Not Specified	0	1	0	3
Double-Blind or Continued Treatment Did not ingest Double-Blind Treatment	0	3	0	0

Baseline Characteristics

Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + ADT Lead-in n=1022 Participants Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.
Age, Continuous	44.1 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	673 Participants n=5 Participants
Sex: Female, Male Male	349 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	741 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	250 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	18 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	234 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	788 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week 8)

Population: Double-blind Intent-to-Treat (ITT) Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Placebo + ADT (Double-Blind) n=258 Participants Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Cariprazine + ADT (Double-Blind) n=267 Participants Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).
Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline in the Double-Blind Period	25.2 score on a scale Standard Deviation 6.1	25.4 score on a scale Standard Deviation 5.5

PRIMARY outcome

Timeframe: Baseline (Week 8) to Week 16

Population: Double-blind ITT Population included all participants in the double-blind safety population who had a randomization baseline assessment and at least 1 postbaseline assessment of the MADRS total score during the double-blind treatment period.

The MADRS is a clinician-rated scale to assess depressive symptomatology during the past week. Participants are rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating and lack of interest. Each item is scored on a 7-point scale. A score of 0 indicates the absence of symptoms, and a score of 6 indicates symptoms of maximum severity for a total possible score of 0 to 60. A negative change from Baseline indicates improvement. Mixed-effects model for repeated measures (MMRM) with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.

Outcome measures

Outcome measures
Measure	Placebo + ADT (Double-Blind) n=258 Participants Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Cariprazine + ADT (Double-Blind) n=267 Participants Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in the Double-Blind Period	-7.5 score on a scale Standard Error 0.5	-7.7 score on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline (Week 8) to Week 16

The Sheehan Disability Scale (SDS) is a 3-item patient-rated questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. All items are rated on an 11-point continuum from 0 (no impairment) to 10 (most severe). The 3 individual scores are summed for a total possible score of 0 (unimpaired) to 30 (highly impaired). A negative change from Baseline indicates improvement. MMRM with treatment group, study center, visit, and treatment group-by-visit interaction as fixed effects, and the baseline value and baseline by-visit interaction as the covariates was used for analyses.

Outcome measures

Outcome measures
Measure	Placebo + ADT (Double-Blind) n=258 Participants Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Cariprazine + ADT (Double-Blind) n=267 Participants Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).
Change From Baseline in Sheehan Disability Scale (SDS) Score in the Double-Blind Period	-3.1 score on a scale Standard Error 0.5	-3.7 score on a scale Standard Error 0.5

Adverse Events

Placebo + ADT Lead-in

Serious events: 9 serious events

Other events: 261 other events

Deaths: 0 deaths

Placebo + ADT (Double-Blind)

Serious events: 3 serious events

Other events: 50 other events

Deaths: 0 deaths

Cariprazine + ADT (Double-Blind)

Serious events: 1 serious events

Other events: 101 other events

Deaths: 0 deaths

Placebo + ADT (Continued Treatment)

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo + ADT Lead-in n=1022 participants at risk Antidepressant therapy (ADT) as prescribed by the investigator plus single-blind placebo for 8 weeks.	Placebo + ADT (Double-Blind) n=258 participants at risk Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to dose-matched placebo, once per day, oral administration plus ADT for 8 weeks (up to Week 16).	Cariprazine + ADT (Double-Blind) n=269 participants at risk Following the 8 week ADT plus single blind placebo lead-in period participants were randomized to cariprazine, 1.5 to 4.5 milligrams (mg) per day, oral administration plus ADT for 8 weeks (up to Week 16).	Placebo + ADT (Continued Treatment) n=270 participants at risk Following the 8 week ADT plus single blind placebo lead-in period, participants who were ADT responders continued treatment with ADT plus placebo for an additional 8 weeks.
Gastrointestinal disorders Nausea	8.9% 91/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	3.9% 10/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	6.3% 17/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Gastrointestinal disorders Diarrhoea	5.6% 57/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Infections and infestations Nasopharyngitis	0.00% 0/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	5.2% 14/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Nervous system disorders Headache	8.9% 91/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	5.8% 15/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	8.2% 22/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Nervous system disorders Somnolence	0.00% 0/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	1.2% 3/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	5.2% 14/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Psychiatric disorders Insomnia	6.7% 68/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	7.0% 18/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	8.2% 22/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Nervous system disorders Akathisia	0.00% 0/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	3.1% 8/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	17.1% 46/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.
Psychiatric disorders Restlessness	0.00% 0/1022 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	1.9% 5/258 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	8.6% 23/269 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.	0.00% 0/270 • First dose of study drug up to 30 days past last dose of study drug (Up to 12 Weeks for the ADT Lead-In arm) and up to an additional 12 weeks for the Double-Blind and Continued Treatment arms Other Adverse Events at a threshold of \>=2% were analyzed separately for Lead-in, Double-Blind and Continued Treatment arms.

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