Dataset Information

A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Maintenance Treatment in Adults with Schizophrenia.

ABSTRACT: Background:Brexpiprazole is a serotonin-dopamine activity modulator with efficacy in acute schizophrenia and relapse prevention. The aim of this Phase 3, multicenter study was to assess the long-term safety, tolerability, and efficacy of treatment with brexpiprazole flexible-dose 1-4 mg/d. Methods:Patients rolled over into this 52-week open-label study (amended to 26 weeks towards the end) from 3 randomized, double-blind, placebo-controlled Phase 3 studies. De novo patients, not part of the previous studies, were also enrolled. The primary outcome variable was the frequency and severity of treatment-emergent adverse events. Efficacy was assessed as a secondary objective using the Positive and Negative Syndrome Scale and the Personal and Social Performance scale. Results:A total of 1072 patients was enrolled (952 for 52 weeks and 120 for 26 weeks), 47.4% of whom completed the study. Among patients who took at least one dose of brexpiprazole, 14.6% discontinued due to treatment-emergent adverse events, most commonly schizophrenia (8.8%) and psychotic disorder (1.5%). Treatment-emergent adverse events with an incidence of ?5% were schizophrenia (11.6%), insomnia (8.6%), weight increased (7.8%), headache (6.4%), and agitation (5.4%). Most treatment-emergent adverse events were mild or moderate in severity. The mean increase in body weight from baseline to week 26 was 1.3 kg and to week 52 was 2.1 kg. There were no clinically relevant findings related to prolactin, lipids, and glucose, or QT prolongation. On average, patients' symptoms and functioning showed continual improvement. Conclusions:Treatment with brexpiprazole 1-4 mg/d was generally well tolerated for up to 52 weeks in patients with schizophrenia. ClinicalTrials.gov identifier:NCT01397786 (https://clinicaltrials.gov/show/NCT01397786).

SUBMITTER: Forbes A

PROVIDER: S-EPMC5932477 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Maintenance Treatment in Adults with Schizophrenia.

Forbes Andy A Hobart Mary M Ouyang John J Shi Lily L Pfister Stephanie S Hakala Mika M

The international journal of neuropsychopharmacology 20180501 5

<h4>Background</h4>Brexpiprazole is a serotonin-dopamine activity modulator with efficacy in acute schizophrenia and relapse prevention. The aim of this Phase 3, multicenter study was to assess the long-term safety, tolerability, and efficacy of treatment with brexpiprazole flexible-dose 1-4 mg/d.<h4>Methods</h4>Patients rolled over into this 52-week open-label study (amended to 26 weeks towards the end) from 3 randomized, double-blind, placebo-controlled Phase 3 studies. De novo patients, not p ...[more]

PMID: 29415258

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Project description:BackgroundAripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for gluteal administration every 2 months, currently being investigated for the treatment of schizophrenia and bipolar I disorder (BP-I). The objectives of this trial were to evaluate the safety and tolerability of Ari 2MRTU 960, and the similarity of aripiprazole plasma concentrations following administration of Ari 2MRTU 960 or aripiprazole once-monthly 400 mg (AOM 400), in adults with schizophrenia or BP-I.MethodsThis was a 32-week open-label study. Eligible participants were randomized 1:1 to receive Ari 2MRTU 960 every 56 ± 2 days (four injections scheduled) or AOM 400 every 28 ± 2 days (eight injections scheduled). Participants received overlapping oral antipsychotic treatment with the first administration of study drug (there was no oral overlap for participants stabilized on AOM 400). Safety, tolerability, and pharmacokinetics (PK) were evaluated throughout the study. Primary safety endpoints included reported adverse events, injection site reactions, and extrapyramidal symptoms. Primary PK endpoints were plasma concentration of aripiprazole 56 days after the fourth dose of Ari 2MRTU 960 and 28 days after the eighth dose of AOM 400, and area under the concentration-time curve (AUC) from Day 0 to 56 postdose after the fourth dose of Ari 2MRTU 960, or AUC from Day 0 to 28 after the seventh and eighth doses of AOM 400.ResultsOf the 266 participants enrolled (schizophrenia, n = 185; BP-I, n = 81), 132 were randomized to receive Ari 2MRTU 960 and 134 were randomized to receive AOM 400. The majority (66.2%) of participants were male; 72.9% were Black or African American, and mean age was 47.3 years; demographic characteristics and baseline disease characteristics were generally well balanced between groups. Study completion rate was 77.3% in the Ari 2MRTU 960 group and 68.7% in the AOM 400 group. The incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 (71.2%) and AOM 400 (70.9%). The most frequently reported TEAEs were increased weight (Ari 2MRTU 960: 22.7%; AOM 400: 20.9%) and injection-site pain (Ari 2MRTU 960: 18.2%; AOM 400: 9.0%). The geometric means ratio (GMR) of aripiprazole plasma concentrations on the last day following the final dosing for Ari 2MRTU 960 versus AOM 400 was 1.011 (90% confidence interval [CI] 0.893-1.145), and the GMR of aripiprazole plasma exposure (area under the concentration-time curve) over the fourth Ari 2MRTU 960 dosing interval versus the seventh and eighth AOM 400 dosing intervals was 1.006 (90% CI 0.851-1.190).ConclusionsAri 2MRTU 960 was generally well tolerated in adults with schizophrenia or BP-I, with a safety profile comparable with that of AOM 400, and aripiprazole exposure equivalent to that with AOM 400 (ClinicalTrials.gov identifier: NCT04030143, registered on 23 July 2019).

Project description:BackgroundProbiotics are among the most commonly used dietary supplements and evidence of their efficacy is increasing. Despite the long historical use of probiotics, some experts suggest that additional research is necessary to understand their potential risks.ObjectivesMain aims of this study were to assess short-term tolerability and safety of a new, high colony-forming unit count, multi-strain probiotic supplement. Exploratory objectives included evaluating effects on gut microbial composition.MethodsTen healthy adults were enrolled in a single-arm, open-label study. Over a 10-day period, participants consumed a once daily probiotic capsule (2.1 x 1011 CFU) containing Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Lactobacillus plantarum Lp-115, Lactobacillus rhamnosus GG, Lactobacillus rhamnosus HN001, Bifidobacterium lactis Bi-07, Bifidobacterium lactis Bl-04, and Bifidobacterium lactis HN019. The primary measure of tolerability pertained to whether or not participants completed the study. Secondary safety measures included clinical biomarkers from a routine metabolic panel and a complete blood count. Exploratory measures included stool microbiota counts.ResultsAll participants completed the study and there were no serious adverse events. All documented adverse events were prompted by the investigators and the most commonly reported symptoms were gastrointestinal. There was a single instance of a biomarker abnormality in one individual. Overall, decreases in total bilirubin and aspartate aminotransferase, and increases in stool levels of Lactobacillus species, Faecalibacterium prausnitzii, and Akkermansia muciniphila (P < .05) were observed over the course of the study.ConclusionsThe findings of this study suggest the multi-strain probiotic supplement was well-tolerated and most likely safe. Changes in liver function measures suggest the probiotics could potentially impact liver health. Stool microbiota changes suggest the probiotic could potentially impact gut health by affecting levels of intestinal microbiota that have been described as bioindicators of health and potential keystone species. However, additional research is necessary to follow up on the exploratory findings of this preliminary work.

Dataset Information

A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Maintenance Treatment in Adults with Schizophrenia.

Publications

A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Maintenance Treatment in Adults with Schizophrenia.

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