NCT03739203

The Objective of This Study is to Evaluate the Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD) Who Have Had an Inadequate Response to Antidepressants Alone

Completed Phase 3 Results posted Last updated 21 September 2022

What this trial tests

Phase 3 trial testing Cariprazine in Major Depressive Disorder in 752 participants. Completed in 6 September 2021.

Timeline

10 November 2018

Primary endpoint
6 September 2021

6 September 2021

Quick facts

Lead sponsor	AbbVie
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	752
Start date	10 November 2018
Primary completion	6 September 2021
Estimated completion	6 September 2021
Sites	112 locations across Finland, Slovakia, Serbia, Poland, Canada, Puerto Rico, United States, Czechia

Drugs / interventions tested

• Cariprazine (CARIPRAZINE) — full drug profile →
• Placebo
• Antidepressant Therapy (ADT) — full drug profile →

Conditions studied

• Major Depressive Disorder — all drugs for Major Depressive Disorder →

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 65, any sex, with Major Depressive Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) Total Score Primary · Baseline and Week 6

The 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 item 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. The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change from Baseline indicates improvement. Mix

Group	Value	95% CI
Placebo + ADT	-13.4	± 0.70
Cariprazine 1.5 mg/Day + ADT	-13.8	± 0.69
Cariprazine 3 mg/Day + ADT	-14.8	± 0.70

Change From Baseline to Week 6 in the Clinical Global Impressions-Severity (CGI-S) Score Secondary · Baseline and Week 6

The CGI-S is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analyses.

Group	Value	95% CI
Placebo + ADT	-1.4	± 0.09
Cariprazine 1.5 mg/Day + ADT	-1.4	± 0.09
Cariprazine 3 mg/Day + ADT	-1.6	± 0.09

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose of study drug until 30 days after the last dose of study drug (up to 12 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo + ADT

Serious: 2/250 (1%)

Deaths: 1/250

Cariprazine 1.5 mg/Day + ADT

Serious: 3/250 (1%)

Deaths: 0/250

Cariprazine 3 mg/Day + ADT

Serious: 1/251 (0%)

Deaths: 0/251

Serious adverse events (8 terms)

Reaction	System	Placebo + ADT	Cariprazine 1.5 mg/Day + ADT	Cariprazine 3 mg/Day + ADT
ATRIAL FIBRILLATION	Cardiac disorders	—	—	—
INTESTINAL OBSTRUCTION	Gastrointestinal disorders	—	—	—
DEATH	General disorders	—	—	—
ANIMAL BITE	Injury, poisoning and procedural complications	—	—	—
FALL	Injury, poisoning and procedural complications	—	—	—
FIBULA FRACTURE	Injury, poisoning and procedural complications	—	—	—
LIGAMENT SPRAIN	Injury, poisoning and procedural complications	—	—	—
SUICIDE ATTEMPT	Psychiatric disorders	—	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Placebo + ADT	Cariprazine 1.5 mg/Day + ADT	Cariprazine 3 mg/Day + ADT
AKATHISIA	Nervous system disorders	—	—	—
HEADACHE	Nervous system disorders	—	—	—
INSOMNIA	Psychiatric disorders	—	—	—
SOMNOLENCE	Nervous system disorders	—	—	—
NAUSEA	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: ATRIAL FIBRILLATION, INTESTINAL OBSTRUCTION, DEATH, ANIMAL BITE, FALL, FIBULA FRACTURE, LIGAMENT SPRAIN, SUICIDE ATTEMPT.

Data from ClinicalTrials.gov NCT03739203 adverse events section.

Sponsor's own description

The objective of this study is to evaluate the efficacy, safety and tolerability of cariprazine as an adjunctive treatment to antidepressant therapy (ADT) in patients with MDD who have had an inadequate response to antidepressants alone.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de-risk trial programmes of novel agents.
   Correll CU, Solmi M, Cortese S, Fava M, et al · · 2023 · cited 90× · PMID 36640403 · DOI 10.1002/wps.21056
2. Cariprazine for the Adjunctive Treatment of Major Depressive Disorder in Patients With Inadequate Response to Antidepressant Therapy: Results of a Randomized, Double-Blind, Placebo-Controlled Study.
   Riesenberg R, Yeung PP, Rekeda L, Sachs GS, et al · · 2023 · cited 10× · PMID 37585254 · DOI 10.4088/jcp.22m14643
3. Safety and tolerability of cariprazine for the adjunctive treatment of major depressive disorder: a pooled analysis of phase 2b/phase 3 clinical trials.
   Thase ME, Yeung PP, Rekeda L, Liu M, et al · · 2025 · cited 5× · PMID 38277187 · DOI 10.1097/yic.0000000000000528
4. ACNP 63rd Annual Meeting: Poster Abstracts P1-P304
   · 2024
5. ACNP 62nd Annual Meeting: Poster Abstracts P251 – P500
   · 2023