Dataset Information

Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration.

ABSTRACT:

Background

Two open-label, randomized, parallel-arm studies compared pharmacokinetics, safety, and tolerability of aripiprazole once-monthly 400 mg following deltoid vs gluteal injection in patients with schizophrenia.

Methods

In the single-dose study, 1 injection of aripiprazole once-monthly 400 mg in the deltoid (n=17) or gluteal (n=18) muscle (NCT01646827) was administered. In the multiple-dose study, the first aripiprazole once-monthly 400 mg injection was administered in either the deltoid (n=71) or gluteal (n=67) muscle followed by 4 once-monthly deltoid injections (NCT01909466).

Results

After single-dose administration, aripiprazole exposure (area under the concentration-time curve) was similar between deltoid and gluteal administrations, whereas median time to maximum plasma concentration was shorter (7.1 [deltoid] vs 24.1 days [gluteal]) and maximum concentration was 31% higher after deltoid administration. In the multiple-dose study, median time to maximum plasma concentration for deltoid administration was shorter (3.95 vs 7.1 days), whereas aripiprazole mean trough concentrations, maximum concentration, and area under the concentration-time curve were comparable between deltoid and gluteal muscles (historical data comparison). Multiple-dose pharmacokinetic results for the major metabolite, dehydro-aripiprazole, followed a similar pattern to that of the parent drug for both deltoid and gluteal injection sites. Safety and tolerability profiles were similar after gluteal or deltoid injections. Based on observed data, minimum aripiprazole concentrations achieved by aripiprazole once-monthly 400 mg are comparable with those of oral aripiprazole 15 to 20 mg/d.

Conclusions

The deltoid muscle is a safe alternative injection site for aripiprazole once-monthly 400 mg in patients with schizophrenia.

SUBMITTER: Raoufinia A

PROVIDER: S-EPMC5409034 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration.

Raoufinia Arash A Peters-Strickland Timothy T Nylander Anna-Greta AG Baker Ross A RA Eramo Anna A Jin Na N Bricmont Patricia P Repella Jennifer J McQuade Robert D RD Hertel Peter P Larsen Frank F

The international journal of neuropsychopharmacology 20170401 4

<h4>Background</h4>Two open-label, randomized, parallel-arm studies compared pharmacokinetics, safety, and tolerability of aripiprazole once-monthly 400 mg following deltoid vs gluteal injection in patients with schizophrenia.<h4>Methods</h4>In the single-dose study, 1 injection of aripiprazole once-monthly 400 mg in the deltoid (n=17) or gluteal (n=18) muscle (NCT01646827) was administered. In the multiple-dose study, the first aripiprazole once-monthly 400 mg injection was administered in eith ...[more]

PMID: 28204607

Similar Datasets

Project description:IntroductionFew studies have compared adherence between long-acting injectable antipsychotics, especially for newer agents like aripiprazole once-monthly 400 mg (AOM 400; aripiprazole monohydrate) and oral antipsychotics, in patients with schizophrenia or bipolar I disorder (BD-I) in a real-world setting.MethodsTwo separate retrospective cohort analyses using Truven MarketScan data from January 1, 2012 to June 30, 2016 were conducted to compare medication adherence and discontinuation in patients with schizophrenia or BD-I who initiated treatment with AOM 400 vs. patients changed from one oral antipsychotic monotherapy to another. Adherence was defined as proportion of days covered (PDC) ≥ 0.80 in the year following the index date. Linear regression models examined the association between AOM 400 and oral antipsychotic cohorts and medication adherence. Kaplan-Meier curves and Cox regression estimated time to and risk of discontinuation, while adjusting for baseline covariates. A sensitivity analysis was conducted using a combination of propensity score matching and exact matching to create matched cohorts.ResultsFinal cohort sizes were as follows-Schizophrenia: AOM 400 n = 408, oral antipsychotic n = 3361; BD-I: AOM 400 n = 413, oral antipsychotic n = 15,534. In patients with schizophrenia, adjusted mean PDC was higher in patients in the AOM 400 cohort vs. the oral antipsychotic cohort (0.57 vs. 0.48 P < 0.001), and patients in the oral antipsychotic cohort had a higher risk of discontinuing treatment vs. the AOM 400 cohort (HR 1.45, 95% CI 1.29-1.64). For patients with BD-I, adjusted mean PDC was higher for the AOM 400 cohort (0.59 vs. 0.44, P < 0.001), and patients in the oral antipsychotic cohort had a higher risk of discontinuation (HR 1.71, 95% CI 1.53-1.92).ConclusionsIn a real-word setting, AOM 400 resulted in a significantly higher percentage of patients with a PDC ≥ 0.80 and significantly longer time to treatment discontinuation compared to patients with schizophrenia or BD-I who received treatment with an oral antipsychotic.FundingOtsuka Pharmaceutical Development and Commercialization, Inc. and Lundbeck.

Project description:Objective: To evaluate the effect of aripiprazole once-monthly 400 mg (AOM 400; Abilify Maintena®) on symptom stability in acute treatment and maintenance therapy settings in patients with schizophrenia. Methods: Results were analyzed from two pivotal maintenance studies (Studies 246 and 247), a long-term (52 weeks), open-label extension of these studies (Study 248), an open-label, mirror-image study in patients switching from oral to long-acting injectable antipsychotic therapy (Study 283), and a study of AOM 400 in the acute setting (Study 291). Symptom stability was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI) scale (CGI-Severity of Illness and CGI-Improvement). Results are reported for the total study population and in subgroups stratified by age. Results: In Study 246, AOM 400 resulted in significantly greater improvements from baseline vs placebo on all measures of symptom stability, with improvements maintained through 52 weeks. In Study 247, a non-inferiority study, AOM 400 resulted in improvements in PANSS and CGI scores comparable or significantly greater at all timepoints vs oral aripiprazole. In Study 248, AOM 400 resulted in the long-term stability of symptom improvements from the earlier studies. In Study 283, AOM 400 resulted in significant improvements from baseline in PANSS and CGI scores over 24 weeks. In Study 291, AOM 400 resulted in significantly greater improvements from baseline in PANSS and CGI scores vs placebo at all post-baseline timepoints. In post hoc analyses, AOM 400 showed similar efficacy in symptom improvement in adult patients aged ≤35 years and >35 years, with some evidence of a larger treatment effect on PANSS negative symptoms among younger patients in the acute treatment setting. Conclusion: In acute treatment and maintenance therapy settings, AOM 400 was effective in the rapid stabilization and long-term maintenance of symptoms in patients with schizophrenia.

Project description:To compare hospitalization rates in patients with schizophrenia treated prospectively with aripiprazole once-monthly 400 mg (AOM 400; an extended-release injectable suspension) vs the same patients' retrospective rates with their prior oral anti-psychotic therapy.Multi-center, open-label, mirror-image, naturalistic study in a community setting in North America. Patients who required a change in treatment and/or would benefit from long-acting injectable anti-psychotic therapy were treated prospectively for 6 months with AOM 400. Retrospective data on hospitalization rates were obtained.ClinicalTrials.gov: NCT01432444.The proportion of patients with ? 1 psychiatric inpatient hospitalization with oral anti-psychotic therapy examined retrospectively (months -4 to -1 before oral conversion) and after switching to AOM 400 (months 4-6 after initiating AOM 400).Psychiatric hospitalization rates were significantly lower when patients were treated with AOM 400 compared with oral anti-psychotic therapy both in the 3-month primary efficacy sample (2.7% [n = 9/336] vs 27.1% [n = 91/336], respectively; p < 0.0001) and in the total sample (6-month prospective rate: 8.8% [n = 38/433] vs 6-month retrospective rate: 38.1% [n = 165/433]; p < 0.0001). Discontinuations due to adverse events (AEs) during cross-titration were lower in patients cross-titrated on oral aripiprazole for >1 and <4 weeks (2.9% [n = 7/239]) compared with patients cross-titrated for ? 1 week (10.4% [n = 5/48]). The most common treatment-emergent AEs during the prospective treatment phase were insomnia (6.7% [n = 29/431]) and akathisia (6.5% [n = 28/431]). Patient-rated injection-site pain decreased from the first injection to the last visit.In a community setting, patients with schizophrenia demonstrated significantly lower psychiatric hospitalization rates after switching from their prior oral anti-psychotic therapy to AOM 400. Patients served as their own control, and thus an active control group was not included in this study. Confounding factors, such as insurance coverage and availability of hospital beds, were not examined here and deserve further consideration.

Project description:BACKGROUND:The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. METHODS:This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. RESULTS:Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (<?10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. CONCLUSION:AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Project description:ObjectiveThis study aims to compare the hospitalization rate in individuals with schizophrenia who started their treatment with aripiprazole once monthly (AOM400) or atypical oral antipsychotics (OA) in Spain.MethodsThis is an observational and retrospective study based on the electronic medical records from the BIG-PAC database. The study population consisted of individuals diagnosed with schizophrenia who initiated their treatment with AOM400 (AOM cohort) or atypical OA (OA cohort) from 01/01/2017 to 31/12/2019. A 1:1 propensity score matching (PSM) procedure was conducted to match individuals of both cohorts. The number and duration of hospitalizations, persistence to treatment, healthcare resources use, and costs were analyzed after 12 months.ResultsAfter the PSM, 1,017 individuals were included in each cohort [age: 41.4 years (SD: 10.6); males: 54.6%]. During the follow-up period, the AOM cohort had a 40% lower risk of hospitalization than the OA group [HR: 0.60 (95% confidence interval, CI: 0.49-0.74)]. The median time to the first hospitalization was longer in individuals with AOM400 compared to those with OA (197 days compared to 174 days; p < 0.004), whereas hospital admissions were shorter (AOM400: 6 compared to OA: 11 days; p < 0.001). After 12 months, individuals receiving AOM400 were more persistent than those with OA (64.9% compared to 53.7%; p < 0.001). The OA cohort required more healthcare resources, mainly visits to primary care physicians, specialists, and emergency rooms than those receiving AOM400 (p ≤ 0.005 in all comparisons). AOM400 reduced the costs of hospitalizations, and emergency room, specialist and primary care visits by 50.4, 36.7, 16.1, and 10.9%, respectively, in comparison to the treatment with atypical OA. AOM400 led to annual cost savings of €1,717.9 per individual, from the societal perspective.ConclusionAripiprazole once monthly reduces the number and duration of hospitalizations, together with the treatment costs of schizophrenia, as it reduces the use of healthcare resources and productivity losses in these individuals.

Project description:To report the design and preliminary results of a mirror-image study comparing total psychiatric hospitalisation rates pre- and post-switch to aripiprazole once-monthly, an extended release injectable solution.A multi-center, open-label mirror-image study of patients (18-65 years) with schizophrenia to compare total psychiatric hospitalisation rates between retrospective treatment with oral standard-of-care (SOC) anti-psychotics and prospective treatment with aripiprazole once-monthly in a naturalistic community setting in North America. Total psychiatric hospitalisation rates were assessed between retrospective (Months -4 to -1) and prospective treatment periods (Months 4-6) for patients who completed ?3 months aripiprazole once-monthly.One hundred and eighty-three patients entered the prospective phase. After switching to aripiprazole once-monthly, total psychiatric hospitalisation rates for the 3-month prospective period were significantly lower (p?<?0.0001, Exact McNemar's test) compared with the retrospective 3-month period when the same patients received SOC anti-psychotics (6.6% [n?=?8/121] vs 28.1% [n?=?34/121], respectively; rate ratio?=?0.24). Similarly, total psychiatric hospitalisation rates for all patients who entered the prospective treatment phase were significantly lower (p?<?0.0001, Exact McNemar's test) for the prospective 6 months following switch to aripiprazole once-monthly, compared with the retrospective 6-month SOC period (14.2% [n?=?26/183] vs 41.5% [n?=?76/183], respectively; rate ratio?=?0.34). Common treatment-emergent adverse events (occurring in ?5% of patients) were psychotic disorder (7.7%), akathisia (7.2%), and insomnia (7.2%). Discontinuation (all causes) during the prospective phase was 44.8% (n?=?82/183).Mirror-image studies do not include a parallel active control; as each patient serves as their own control, it cannot be determined whether other treatments may have similar effects. Treatment and trial effects may be difficult to separate. Independent factors such as admission patterns, insurance coverage, availability of hospital beds, and community support may influence rates of hospitalisation.Switching to aripiprazole once-monthly substantially reduced total psychiatric hospitalisation rates compared with retrospective rates in the same patients taking oral SOC.

Dataset Information

Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration.

Background

Methods

Results

Conclusions

Publications

Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets