Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale—supportive analyses from a Phase 3 study

CNS Spectrums ◽  
2017 ◽  
Vol 23 (4) ◽  
pp. 284-290 ◽  
Author(s):  
Leslie Citrome ◽  
Robert Risinger ◽  
Andrew J. Cutler ◽  
Yangchun Du ◽  
Jacqueline Zummo ◽  
...  
Keyword(s):  
Scale Score ◽  
Clinical Global Impression ◽  
Response Rates ◽  
Fixed Dose ◽  
Phase 3 ◽  
General Psychopathology ◽  
Syndrome Scale ◽  
Long Acting ◽  
Post Hoc ◽  
Negative Syndrome

ObjectiveAripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.MethodsPatients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.ResultsOf 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.ConclusionAL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.

Réponse thérapeutique, tolérance et sécurité d’emploi du palmitate de palipéridone à dose flexible : une étude prospective chez des patients adultes non-aigus atteints de schizophrénie, après échec d’un traitement par antipsychotiques oraux

2013 ◽  
Vol 28 (S2) ◽  
pp. 107-107
Author(s):  
P. Vidailhet ◽  
A. Schreiner ◽  
P. Bergmans ◽  
P. Cherubin ◽  
E. Rancans ◽  
...  
Keyword(s):  
Clinical Global Impression ◽  
Severity Scale ◽  
Effets Indésirables ◽  
Étude Prospective ◽  
Clinical Global Impression Severity ◽  
Syndrome Scale ◽  
La Substitution ◽  
Negative Syndrome

ObjectifsÉvaluer la tolérance, la sécurité d’emploi et la réponse à un traitement mensuel par palmitate de paliperidone (PP) à doses flexibles chez des patients adultes atteints de schizophrénie, non-aigus mais symptomatiques, après échec d’un traitement par antipsychotiques oraux.MéthodesAnalyse d’un groupe de patients atteints de schizophrénie, non-aigus mais symptomatiques, inclus dans une étude internationale, ouverte, prospective de six mois, évaluant la symptomatologie clinique : PANSS (Positive and Negative Syndrome Scale) et CGIS-S (Clinical Global Impression-Severity Scale), les événements indésirables (EIs) et le changement de poids.RésultatsCinq cent quatre-vingt-treize patients (population en intention de traiter) : 63,1 % d’hommes, âge moyen 38,4 ± 11,8 ans, 78,6 % souffrant de schizophrénie paranoïde. La principale raison de la substitution d’un antipsychotique oral par le PP était un manque d’efficacité (24,3 %). 74,5 % des patients ont terminé l’étude de six mois. Les raisons les plus fréquentes d’arrêt précoce étaient : le choix du patient (9,3 %), des effets indésirables (EIs) (6,1 %), les perdus de vue (3,0 %) et le manque d’efficacité (2,5 %). Le score total moyen à l’échelle PANSS a diminué de 71,5 ± 14,6 à l’inclusion à 59,7 ± 18,1 à la fin de l’étude (soit une différence de −11,7 ± 15,9 points ; 95 % IC 95 % [−13,0 ; −10,5] ; p <0,0001). 64,0 % des patients ont eu une amélioration supérieure ou égale à 20 % du score total à la PANSS et le pourcentage de patients légèrement malades ou moins (CGI-S) est passé de 31,8 à 63,2 %. Les EIs touchant plus de 5 % des patients sont : douleur au site d’injection (12,3 %), insomnie (8,6 %), anxiété (6,7 %), trouble psychotique (6,1 %) et céphalées (5,6 %). Le changement moyen de poids a été de 1,2 ± 5,0 kg (IC 95 % [0,7 ; 1,6]).ConclusionsCes résultats confirment la bonne tolérance et l’efficacité thérapeutique du PP à doses flexibles chez des patients non aigus atteints de schizophrénie, après échec d’un traitement par antipsychotiques oraux.

Long-Term Improvement in Efficacy and Safety After Switching to Ziprasidone in Stable Outpatients with Schizophrenia

CNS Spectrums ◽  
2008 ◽  
Vol 13 (10) ◽  
pp. 898-905 ◽  
Author(s):  
George M. Simpson ◽  
Cedric J. O'Gorman ◽  
Antony Loebel ◽  
Ruoyong Yang
Keyword(s):  
Clinical Global Impression ◽  
Open Label ◽  
Conventional Antipsychotics ◽  
Syndrome Scale ◽  
Number Of Patients ◽  
Severity Scores ◽  
Intent To Treat ◽  
Study Designs ◽  
Negative Syndrome

ABSTRACTIntroduction:The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies.Methods:These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data.Results:Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (−4.3 [P≤.01]), PANSS negative scores (−2.4 [P≤.0001]), and Clinical Global Impression of severity score (−0.3 [P≤.001]). Completers showed significant improvement in mean PANSS total scores (−10.2 [P<.0001]), PANSS positive scores (−2.7 [P<.0001]), PANSS negative scores (−2.7 [P<.001]), and Clinical Global Impression of severity scores (−0.6 [P<.0001]).Conclusion:Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval ≥500 msec.

Patients in the early phases of schizophrenia and schizoaffective disorders effectively treated with risperidone long-acting injectable

2005 ◽  
Vol 19 (5_suppl) ◽  
pp. 5-14 ◽  
Author(s):  
E. Parellada ◽  
R. Andrezina ◽  
V. Milanova ◽  
P. Glue ◽  
M. Masiak ◽  
...  
Keyword(s):  
Symptom Improvement ◽  
Treatment Change ◽  
Open Label ◽  
Schizoaffective Disorders ◽  
Direct Initiation ◽  
Syndrome Scale ◽  
Previous Medication ◽  
Long Acting ◽  
Negative Syndrome ◽  
Early Phases

The efficacy and safety of risperidone long-acting injectable (RLAI) was investigated in patients in the early phases of schizophrenia and schizoaffective disorders (≤ 3 years). Patients who required a treatment change received RLAI (2-weekly gluteal injections of 25, 37.5 or 50mg, per clinical judgement), without an oral risperidone run-in phase. A total of 382 patients were included in this 6-month open-label study; 73% of patients completed the study. A total of 84% had schizophrenia with a median duration of 1.0 year since diagnosis. Previous medications were mainly atypical antipsychotics (70%) and depot neuroleptics (24%). The main reasons for treatment change were non-compliance (42%) and insufficient efficacy (31%) of previous medication. The total Positive and Negative Syndrome Scale (PANSS) and all its subscale scores improved significantly (p ≤ 0.0001), with 40% of patients showing a 20% improvement on total PANSS. Global Assessment of Functioning, quality of life, patient satisfaction and movement disorders also improved significantly. Tolerability of RLAI was generally good and no unexpected adverse events were reported. The ensured delivery of medication with RLAI resulted in significant symptom improvement in this patient population. Direct initiation of RLAI is well accepted by patients. RLAI might represent a novel option for patients in the early phases of psychosis.

scholarly journals Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis

2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Odds Ratio ◽  
Airflow Obstruction ◽  
Chronic Obstructive ◽  
Phase 3 ◽  
Muscarinic Antagonist ◽  
Long Acting ◽  
Post Hoc ◽  
Patient Subgroups ◽  
Severe Copd

Abstract Background: Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV 1 ) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials (revefenacin 175 µg [n = 395] and placebo [n = 417]) was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV 1 , St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. We included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV 1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% in FEV 1 ) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV 1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. There was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years. Conclusions: Revefenacin showed significantly greater improvements in FEV 1 versus placebo in the ITT population and all subgroups. There were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Revefenacin could be a therapeutic option among patients with markers of more severe COPD.

scholarly journals Prognostic model of the risk of hyperprolactinemia in patients with schizophrenia receiving antipsychotic therapy

2020 ◽  
pp. 3-10
Author(s):  
Д.З. Падерина ◽  
М.Б. Фрейдин ◽  
О.Ю. Федоренко ◽  
В.Н. Стегний ◽  
С.А. Иванова
Keyword(s):  
Clinical Global Impression ◽  
Side Effect ◽  
Prognostic Model ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Transporter Gene ◽  
Antipsychotic Therapy ◽  
Drug Induced ◽  
Syndrome Scale ◽  
Negative Syndrome

Использование антипсихотических средств ассоциировано с повышенным уровнем пролактина. Лекарственно-индуцированная гиперпролактинемия (ГП) имеет не только краткосрочные, но и долгосрочные последствия, которые могут серьезно повлиять на качество жизни пациента. Клинические проявления ГП включают гинекомастию, галакторею, нарушения менструального цикла, сексуальные дисфункции, бесплодие, а также значимый рост вероятности развития остеопороза и онкологических заболеваний. В развитии данного побочного эффекта антипсихотической терапии участвуют не только экзогенные, но и генетические факторы. Целью данной работы было исследование клинических и молекулярно-генетических факторов развития лекарственно-индуцированной ГП и создание прогностической модели риска развития ГП, которая в перспективе может быть использована для оптимизации и персонализации назначаемой терапии при лечении шизофрении. Исследование проведено в выборке русских, проживающих в Западно-Сибирском регионе России, больных шизофренией (n=446). Средний возраст пациентов составил 41,5 ± 13,4 года (возрастной диапазон - от 18 до 65 лет). Клиническая симптоматика оценивалась по шкалам позитивных и негативных синдромов (Positive and Negative Syndrome Scale - PANSS), общего клинического впечатления (Clinical Global Impression - CGI), оценки побочного действия (Udvalg for Kliniske Undersogelser Scale - UKU), на всех пациентов заполнялся модифицированный вариант карты стандартизированного описания больного шизофренией. На основании содержания гормона пролактина в сыворотке крови были выделены подгруппы пациентов с ГП (n=227) и с нормальным уровнем пролактина (n=219). Выполнен молекулярно-генетический анализ 88 полиморфных вариантов генов серотониновых (HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B) и дофаминовых (DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4) рецепторов, дофаминового транспортера SLC6A3, переносчика норадреналина SLC6A2, системы ферментов цитохромов P450 (CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2), катехол-О-метилтрансферазы СОМТ, p-глутатион S-трансферазы GSTP1, ATXN1, KREMEN1 и пролактина PRL. Получена прогностическая модель с включением генетических маркеров «rs1176744» (HTR3B), «rs10042486» (HTR1A), «rs936461» (DRD4), «rs179997» (ATXN1), «rs1076562» (DRD2), «rs3773678» (DRD3), «rs167771» (DRD3), «rs1587756» (DRD3), «rs134655» (KREMEN1),»rs3892097» (CYP2D6*4), «rs1341239» (PRL), «rs4975646» (SLC6A3), «rs13333066» (SLC6A2), а также негенетических факторов, таких как пол, возраст и доза антипсихотика в хлорпромазиновом эквиваленте (CPZeq). Разработанную фармакогенетическую панель можно рассматривать в качестве биологического предиктора развития антипсихотик-индуцированной ГП при шизофрении до назначения фармакотерапии. The use of antipsychotics is associated with elevated prolactin levels. Drug-induced hyperprolactinemia (HP) has not only short-term, but also long-term consequences, which can seriously affect the patient’s quality of life. Clinical manifestations of HP include gynecomastia, galactorrhea, menstrual irregularities, sexual dysfunctions, infertility, as well as a significant increase in the likelihood of developing osteoporosis and cancer. Not only exogenous, but also genetic factors are involved in the development of this side effect of antipsychotic therapy. The aim of this work was to study the clinical and molecular genetic factors of the development of drug-induced HP and the creation of a prognostic model of the risk of developing HP, which in the future can be used to optimize and personalize the prescribed therapy in the treatment of schizophrenia. The study was conducted in populations of russians with schizophrenia (n = 446), living in the West Siberian region of Russia. The average age of patients was 41,5 ± 13,4 years (18 - 65 age range). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI), the side effect rating scale (Udvalg for Kliniske Undersogelser Scale - UKU), and a modified version of the card of a standardized description of patient with schizophrenia. Based on the results on the serum prolactin level patients were divided into subgroups: with HP (n = 227) and with normal prolactin levels (n = 219). Molecular genetic analysis of 88 polymorphic variants of serotonin receptors genes (HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B) and dopamine receptors genes (DRD1, DRD2, DRD2 / ANKK1, DRD3, DRD4), dopamine transporter gene SLC6A3, noradrenaline transporter gene SLC6A2, genes of the cytochrome P450 enzymes (CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2), gene of catechol-O-methyltransferase COMT, gene of glutathione S-transferase P (GSTP1), genes ATXN1, KREMEN1 and prolactin gene PRL was performed. A prognostic model was obtained with the inclusion of the genetic markers “rs1176744” (HTR3B), “rs10042486” (HTR1A), “rs936461” (DRD4), “rs179997” (ATXN1), “rs1076562” (DRD2), “rs3773678” (DRD3), “rs167771” (DRD3), “rs1587756” (DRD3), “rs134655” (KREMEN1), “rs3892097” (CYP2D6*4), “rs1341239” (PRL),”rs4975646” (SLC6A3),”rs1333302” (SLC6A2), as well as non-genetic factors such as gender, age and dose of antipsychotic in chlorpromazine equivalent (CPZeq). The developed pharmacogenetic panel can be considered as biological predictors of the development of antipsychotic-induced HP in schizophrenia before the appointment of pharmacotherapy.

scholarly journals Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis

2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Odds Ratio ◽  
Airflow Obstruction ◽  
Chronic Obstructive ◽  
Phase 3 ◽  
Muscarinic Antagonist ◽  
Long Acting ◽  
Post Hoc ◽  
Patient Subgroups ◽  
Severe Copd

Abstract Background : Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV 1 ) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV 1 , St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included ​ patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV 1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% and ≥200 mL increase in FEV 1 ) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV 1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years. Conclusions: Revefenacin showed significantly greater improvements in FEV 1 versus placebo in the ITT population and all subgroups. There were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Revefenacin could be a therapeutic option among patients with markers of more severe COPD.

scholarly journals Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis

2020 ◽  
Author(s):  
James F. Donohue ◽  
Edward Kerwin ◽  
Chris N. Barnes ◽  
Edmund J. Moran ◽  
Brett Haumann ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Odds Ratio ◽  
Airflow Obstruction ◽  
Chronic Obstructive ◽  
Phase 3 ◽  
Muscarinic Antagonist ◽  
Long Acting ◽  
Post Hoc ◽  
Patient Subgroups ◽  
Severe Copd

Abstract Background: Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 second (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. Methods: A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%–<50% and <30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥12% and ≥200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (>65 and >75 years), and comorbidity risk factors. Results: Revefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio >2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio >2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >75 years. Conclusions: Revefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.

scholarly journals 26 A Phase 3 Study to Determine the Antipsychotic Efficacy and Safety of ALKS 3831 in Adult Patients with Acute Exacerbation of Schizophrenia

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 187-188 ◽  
Author(s):  
Steven G Potkin ◽  
Jelena Kunovac ◽  
Bernard L Silverman ◽  
Adam Simmons ◽  
Ying Jiang ◽  
...  
Keyword(s):  
Weight Gain ◽  
Acute Exacerbation ◽  
Scale Score ◽  
Mean Difference ◽  
Fixed Dose ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Study Objective ◽  
Antipsychotic Efficacy

AbstractBackgroundALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.Study objectiveTo assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.MethodsThis was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).ResultsOf 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.DiscussionTreatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.Funding Acknowledgements: This study was funded by Alkermes, Inc.

scholarly journals Phase 3 Safety and Tolerability Results of the Combination Olanzapine and Samidorphan in Patients with Schizophrenia: The 1 Year ENLIGHTEN-2-Extension

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 155-156
Author(s):  
Rene Kahn ◽  
Bernard Silverman ◽  
Lauren DiPetrillo ◽  
Christine Graham ◽  
Ying Jiang ◽  
...  
Keyword(s):  
Weight Gain ◽  
Waist Circumference ◽  
Extension Study ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Laboratory Parameters ◽  
Syndrome Scale ◽  
Open Label Extension ◽  
Negative Syndrome

AbstractObjectiveCombination olanzapine and samidorphan (OLZ/SAM) is in development for treatment of schizophrenia and bipolar I disorder and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension study (NCT02873208; ENLIGHTEN-2-EXT) in schizophrenia assessed the safety and tolerability of OLZ/SAM. Methods: Patients completing the 24-week, randomized, double-blind, phase 3 ENLIGHTEN−2 study comparing weight gain with OLZ/SAM vs olanzapine were eligible for ENLIGHTEN-2-EXT enrollment. Initial OLZ/SAM doses were based on olanzapine dose (10 or 20 mg) received at the conclusion of ENLIGHTEN-2; subsequent olanzapine dose adjustments were allowed. The samidorphan dose (10 mg) remained fixed throughout. Assessments included adverse events (AEs), weight, waist circumference, metabolic laboratory parameters, and Positive and Negative Syndrome Scale (PANSS) scores. Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.Results265 patients received OLZ/SAM; 167 (63.0%) completed the extension study. Common AEs (= 5%) were weight decreased (n=23; 8.7%), extra dose administered (n=21; 7.9%), headache (n=18; 6.8%), and weight increased (n=16; 6.0%). At week 52, mean (SD) change from baseline for weight and waist circumference was −0.03 (6.216) kg and −0.35 (6.115) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. PANSS total scores remained stable during the extension.ConclusionsOLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.FundingAlkermes, Inc.

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