Topline results were announced from two phase 3 trials evaluating the efficacy and safety of cariprazine as an adjunctive treatment for patients with major depressive disorder.

The multicenter, randomized, double-blind, placebo-controlled studies, 3111-301-001 ( Identifier: NCT03738215) and 3111-302-001 ( Identifier: NCT03739203), included patients 18 years of age and older with major depressive disorder. In both trials, following a screening period of up to 14 days, patients with an inadequate clinical response to their antidepressant monotherapy (ADT) were randomly assigned 1:1:1 to 3 treatment arms: cariprazine 1.5mg orally once daily plus ADT; cariprazine 3mg once daily plus ADT; or placebo plus ADT.

The primary endpoint for both studies was change from baseline to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, a 10-item clinician-rated scale that evaluates depressive symptomatology.

Results from the 3111-301-001 study (N=759) demonstrated that patients treated with cariprazine 1.5mg achieved an improved MADRS total score at week 6 compared with placebo (P =.005). Patients in the cariprazine 3mg arm also had an improvement in the MADRS total score but this was not found to be statistically significant (P =.0727).

The 3111-302-001 study (N=752) did not meet its primary endpoint, though both cariprazine treatment arms demonstrated a numerical improvement over placebo in depressive symptoms based on MADRS total score at week 6. 

No new safety signals were observed in either study. The most common adverse reactions reported were akathisia, nausea, insomnia, headache and somnolence. Full data from the studies will be presented at a future medical meeting.

The Company intends to submit a supplemental New Drug Application to the Food and Drug Administration (FDA) for cariprazine for the adjunctive treatment of major depressive disorder.

Findings from a previously published phase 2/3 study (RGH-MD-75; Identifier: NCT01469377) showed that treatment with cariprazine plus ADT met the primary endpoint demonstrating improved MADRS total scores at week 8 compared with placebo (P =.0114).

“When added to ongoing antidepressant treatment that has produced inadequate response in patients with major depressive disorder, cariprazine has now demonstrated that it can further improve depressive symptoms by providing statistically significant and clinically meaningful improvements compared to placebo in 2 large, well-controlled registrational clinical trials,” said Michael Severino, MD, vice chairman and president, AbbVie.

Cariprazine, an atypical antipsychotic, is marketed under the brand name Vraylar® and is approved for the treatment of schizophrenia in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, and for the treatment of depressive episodes associated with bipolar I disorder in adults.


AbbVie’s cariprazine (Vraylar®) met primary endpoint in phase 3 study as an adjunctive treatment for major depressive disorder. News release. AbbVie. Accessed October 29, 2021.