Efficacy and Safety of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia: a Randomized, Double-Blind, Placebo-Controlled Study

Approximately 51.5% of participants were exposed to brexpiprazole through week 24, but only 23 received brexpiprazole through week 52.

“approximately 51.5% of participants were exposed to brexpiprazole through week 24, but only 23 received brexpiprazole through week 52.”

The relapse-prevention trial was terminated early, and the open-label safety study by Forbes et al was amended to decrease trial length, because the investigative teams noted early collection of adequate safety and efficacy data.

“The relapse-prevention trial8 was terminated early, and the open-label safety study conducted by Forbes et al10 was amended to decrease the trial length, as the investigative teams in both studies noted early collection of adequate safety and efficacy data.”

The majority of patients who did not complete the relapse-prevention trial were discontinued by the sponsor following early termination after the first interim analysis (87 of 202 patients in the maintenance phase).

“the majority of patients who did not complete the trial were discontinued by the sponsor following early termination of the study after the first interim analysis (87 of 202 patients in the maintenance phase).”

At the last visit in the double-blind phase, 79.2% (76/96) of brexpiprazole patients still met stability criteria versus 56.7% (59/104) of placebo patients (P=0.0007).

“at the participant’s last visit in the double-blind phase, 79.2% (76 of 96) of those taking brexpiprazole still met stability criteria vs 56.7% (59 of 104) in the placebo group (χ2 test, P=0.0007).”

In the maintenance phase, increases in fasting triglycerides ≥50 mg/dL occurred in 16.3% of brexpiprazole patients versus 7.4% of placebo patients.

“the only other significant differences between the placebo and treatment groups in the maintenance phase were increases in fasting triglycerides ≥50 mg/dL in 16.3% of the brexpiprazole group vs 7.4% of the placebo group.”

Higher rates of clinically relevant weight gain (≥7%) were more likely to occur in the stabilization phase (11.3%) than in the maintenance phase (5.2%) for patients taking brexpiprazole.

“Higher rates of clinically relevant weight gain, identified as ≥7%, were more likely to occur in the stabilization phase (11.3%) over the maintenance phase (5.2%) for patients taking brexpiprazole.”

Baseline demographics of the randomized maintenance phase included average age 38.8 years in the brexpiprazole group and 41.6 years in the placebo group, average BMI 28.2 and 29.1, roughly 40% female, and approximately 63% white.

“Baseline demographic data for those entering the double-blind maintenance phase (ie, randomized phase) include an average age (SD) of 38.8 (10.7) years old in the brexpiprazole group and 41.6 (10.6) in the placebo group, an average body-mass index (BMI) of 28.2 (6.7) in the brexpiprazole group and 29.1 (6.9) in the placebo group, roughly 40% female, and approximately 63% white.”

In the randomized phase of the relapse-prevention trial, 43.3% of brexpiprazole patients experienced at least one TEAE compared with 55.8% of placebo patients.

“43.3% of patients taking brexpiprazole in the randomized phase experienced at least one TEAE (42 of 97) compared to 55.8% in the placebo group (58 of 104).”

The relapse-prevention trial set two interim analyses after 45 and 68 impending relapse events to minimize patient exposure to placebo if the difference between groups was large enough to end the trial early.

“the investigators also set two interim analyses to occur after 45 and 68 impending relapse events to minimize patient exposure to placebo in the event that the difference between groups was large enough to end the trial early.”

Mean daily dose at the last visit in the maintenance phase of the relapse-prevention trial was 3.6 mg.

“Mean daily dose at the last visit in the maintenance phase was 3.6 mg”

Patients switched from brexpiprazole to placebo in the maintenance phase lost an average of 2.2 kg by their last visit, while patients who stayed on brexpiprazole lost an average of 0.3 kg.

“Patients who were switched from brexpiprazole to placebo in the maintenance phase lost an average of 2.2 kg by their last visit, and patients who stayed on brexpiprazole lost an average of 0.3 kg by their last visit.”

At termination of the relapse-prevention trial, of 524 enrolled participants, 202 entered the maintenance phase, 97 were randomized to brexpiprazole, and 105 to placebo.

“At the time of study termination, of 524 enrolled participants, 202 had entered the maintenance phase and 97 had been randomized to brexpiprazole, with the remaining 105 randomized to placebo.”

In the relapse-prevention trial, time to impending relapse was significantly longer with brexpiprazole than placebo (HR 0.292, 95% CI 0.156-0.548, P<0.0001).

“The primary efficacy analysis, time to impending relapse, was significant, as noted by an HR of 0.292 (95% CI 0.156–0.548, P<0.0001) in favor of brexpiprazole over placebo.”

In the relapse-prevention trial, the placebo group had a greater least-squares mean increase in PANSS score (11.20 points) than the brexpiprazole group (3.25 points; LOCF; ANCOVA P=0.0007).

“greater least-squares mean increase in PANSS score for the placebo group (increase of 11.20 points in the placebo group vs 3.25 points in the brexpiprazole group, last observation carried forward [LOCF]; ANCOVA P=0.0007)”

The interim analysis included 45 relapse events in 167 patients, and the final analysis included 53 relapse events in 200 patients.

“The interim analysis included 45 relapse events in a total of 167 patients, and the final analysis included 53 relapse events in 200 total patients.”

The first interim analysis of the relapse-prevention trial was positive, and the study was terminated.

“The results of the first interim analysis were positive, and the study was terminated.”

In the relapse-prevention trial, brexpiprazole had better scores than placebo on the PSP and Global Assessment of Functioning scales (LOCF P<0.01).

“better scores for those on brexpiprazole vs placebo on the PSP and Global Assessment of Functioning scales (LOCF P<0.01).”

The relapse-prevention trial had a predetermined requirement of 90 impending relapse events to adequately identify brexpiprazole's efficacy as a maintenance agent.

“The study team’s predetermined requirement for the number of events needed to identify brexpiprazole’s efficacy as a maintenance agent adequately was 90 occurrences of impending relapse.”

In the maintenance phase of the relapse-prevention trial, there were no differences between treatment and control groups with respect to EPS scores.

“In the maintenance phase, there were no differences between the treatment and control groups with respect to EPS scores”

The literature search identified published results of three phase III 52-week clinical trials assessing the safety and efficacy of brexpiprazole for the management of schizophrenia.

“The literature search identified published results pertaining to three phase III 52-week clinical trials assessing the safety and efficacy of brexpiprazole for the management of schizophrenia.8–10”

7% of brexpiprazole patients transitioned from normal (<150 mg/dL) to high fasting triglycerides (200 to <500 mg/dL) versus 0 in the placebo group.

“This translated to 7% of patients in the brexpiprazole group transitioning from normal (<150 mg/dL) to high fasting triglycerides (200 to <500 mg/dL) vs 0 in the placebo group.”