A Randomized, Double-Blind, Placebo-Controlled Trial of Aripiprazole Lauroxil in Acute Exacerbation of Schizophrenia

Meltzer, Herbert Y.; Risinger, Robert; Nasrallah, Henry A.; Du, Yangchun; Zummo, Jacqueline; Corey, Lisa M.; Bose, Anjana; Stankovic, Srdjan; Silverman, Bernard L.; Ehrich, Elliot W.

doi:10.4088/jcp.14m09741

Cited by 100 publications

(125 citation statements)

References 11 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…AL was approved for the treatment of schizophrenia in 2015 and is available in three doses, 441 mg, 662 mg, and 882 mg. All three doses are administered monthly, and the 882-mg dose has the option of being administered at 6-week dose intervals. In a large, randomized, placebocontrolled study, both doses of AL evaluated (441 mg and 882 mg) administered every 4 weeks over the course of 12 weeks demonstrated robust efficacy compared with placebo (Meltzer et al, 2015). Results of that study are consistent with earlier studies of oral aripiprazole, which also showed efficacy for the acute treatment of schizophrenia at oral doses ranging from 10 to 30 mg per day (Potkin et al, 2003;Kane et al, 2002).…”

Section: Introductionsupporting

confidence: 80%

“…The study was registered at clinicaltrials.gov (NCT01469039). The primary results have been published (Meltzer et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…Detailed methods were previously reported (Meltzer et al, 2015) and are summarized briefly. Patients satisfying screening eligibility criteria were admitted to an inpatient study unit.…”

Section: Methodsmentioning

confidence: 99%

“…To address the question of AL efficacy for the more symptomatic patients participating in the 12-week pivotal trial (Meltzer et al, 2015), we performed a post hoc analysis of the major response and outcome parameters in patients with the most severe symptoms at baseline. Safety, tolerability, and dose-response were also evaluated.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation

Potkin

Risinger

et al. 2017

Schizophrenia Research

Self Cite

View full text Add to dashboard Cite

Aripiprazole lauroxil (AL), a new long-acting injectable antipsychotic, demonstrated safety and efficacy in treating acute exacerbation symptoms of schizophrenia in a 12-week placebo-controlled trial of two doses of AL (441 mg and 882 mg) administered every 4 weeks. We performed a post hoc analysis of this trial to evaluate the efficacy of AL in the subgroup of patients with severe psychotic symptoms, defined as those with baseline Positive and Negative Syndrome Scale (PANSS) Total score above the median score of 92 (n = 309). Change from baseline to Day 85 in PANSS Total score; Positive, Negative, and General Psychopathology subscale scores; and overall response rate were assessed. Statistically significant and clinically meaningful improvements in PANSS Total score were demonstrated with AL 441 mg and AL 882 mg, with placebo-adjusted differences of −14.7 (p b 0.0001) and −16.6 (p b 0.0001), respectively. Significant and clinically meaningful findings with both doses of AL were also demonstrated for the PANSS subscales and responder rates. Overall responder rates at Day 85 were significantly greater for AL 441 mg (49%; p b 0.001) and 882 mg (61%; p b 0.001) groups vs. placebo (18%). Common adverse events (N 5%) were schizophrenia, akathisia, headache, insomnia, and anxiety. AL demonstrated robust efficacy in treatment of the subgroup of patients experiencing severe psychotic symptoms. Both doses (441 mg and 882 mg) were effective, with numerically greater improvement in symptoms and proportion of responders favoring the higher dose arm. Both doses had a side effect profile consistent with the known safety profile of aripiprazole.

show abstract

Section: Introductionsupporting

confidence: 80%

“…The study was registered at clinicaltrials.gov (NCT01469039). The primary results have been published (Meltzer et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…Detailed methods were previously reported (Meltzer et al, 2015) and are summarized briefly. Patients satisfying screening eligibility criteria were admitted to an inpatient study unit.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation

Potkin

Risinger

et al. 2017

Schizophrenia Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Management involves antipsychotic therapy, with all approved treatments blocking dopamine (D) receptors, particularly D 2 , and second‐generation products blocking serotonin (5‐hydroxytryptamine, 5‐HT), notably 5_HT 2A 2. Present treatments are limited by side effects, such as extrapyramidal symptoms (EPS), metabolic and cardiovascular issues, hyperprolactinemia, as well as sexual and endocrine dysfunctions, that undermine compliance 3, 4, 5, 6, 7…”

mentioning

confidence: 99%

Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy Volunteers and Multiple Doses in Patients with Stable Schizophrenia

Cantillon¹,

Ings²,

Bhat³

2018

Clinical Translational Sci

View full text Add to dashboard Cite

RP5063 is a multimodal dopamine (D)‐serotonin (5‐HT) stabilizer with a high affinity for D2/3/4 and 5‐HT1A/2A/2B/7 receptors and moderate affinity for the serotonin transporter. Single‐dose (10 and 15 mg fasting, 15 mg fed) safety in healthy volunteers and multiple‐dose (10, 20, 50, and 100 mg fed, 10 days) safety and pharmacodynamics in patients with stable schizophrenia were defined in two phase I studies. In the single‐dose study, 32 treatment‐emergent adverse events (TEAEs) were observed. Orthostatic hypotension (n = 6), nausea (n = 5), and dizziness (n = 4) were the most common. One serious adverse event (SAE), seen in a patient who should not have been in the study due to a history of seizures, involved brief seizure‐like symptoms. In the multiple‐dose study, 75 TEAEs were reported. Akathisia (n = 20) and somnolence (n = 14) were the most frequent. No clinically significant changes were seen in glucose or prolactin levels, lipid profiles, weight, or electrocardiographic recordings. In both studies, all TEAEs resolved and none led to withdrawal from the study or death. A pharmacodynamic evaluation reflected significant improvements with RP5063 (P < 0.05) over placebo in an analysis of patients with a baseline Positive and Negative Syndrome Scale (PANSS) score ≥50 for positive subscale scores. Improvements of the Trail Making A and Trail Making B test results were observed for patients treated in the 50 mg dose group for days 5, 10, and 16. These findings indicate that RP5063 is well‐tolerated up to 100 mg and displays promising preliminary clinical behavioral and cognition activity signals in patients with stable disease over a 10‐day period.

show abstract

Aripiprazole (intramuscular) for psychosis-induced aggression or agitation (rapid tranquillisation)

Ostinelli

Jajawi

Spyridi

et al. 2018

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

show abstract

A Randomized, Double-Blind, Placebo-Controlled Trial of Aripiprazole Lauroxil in Acute Exacerbation of Schizophrenia

Abstract: Objective: This study evaluated the efficacy, safety, and tolerability of aripiprazole lauroxil, a novel long-acting injectable atypical antipsychotic, for the treatment of schizophrenia.

Cited by 100 publications

References 11 publications

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation

Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation

Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy Volunteers and Multiple Doses in Patients with Stable Schizophrenia

Aripiprazole (intramuscular) for psychosis-induced aggression or agitation (rapid tranquillisation)

Contact Info

Product

Resources

About