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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

Published online by Cambridge University Press:  19 June 2017

Leslie Citrome
Affiliation:
New York Medical College, Valhalla, New York, USA
Robert Risinger
Affiliation:
NeuroRx Pharmaceuticals, Wilmington, Delaware, USA
Andrew J. Cutler
Affiliation:
Meridien Research, Bradenton, Florida, USA
Yangchun Du
Affiliation:
Alkermes, Inc., Waltham, Massachusetts, USA
Jacqueline Zummo
Affiliation:
Alkermes, Inc., Waltham, Massachusetts, USA
Henry A. Nasrallah
Affiliation:
Saint Louis University School of Medicine, St. Louis, Missouri, USA
Bernard L. Silverman
Affiliation:
Alkermes, Inc., Waltham, Massachusetts, USA
Corresponding
E-mail address:

Abstract

Objective

Aripiprazole 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.

Methods

Patients 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.

Results

Of 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.

Conclusion

AL 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.

Type
Original Research
Copyright
© Cambridge University Press 2017 

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References

1. Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2): 261276.CrossRefGoogle Scholar
2. Carbon, M, Correll, CU. Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectr. 2014; 19(Suppl 1): 3553.CrossRefGoogle Scholar
3. Bobes, J, Arango, C, Garcia-Garcia, M, Rejas, J, CLAMORS Study Collaborative Group. Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study. J Clin Psychiatry. 2010; 71(3): 280286.CrossRefGoogle ScholarPubMed
4. Keefe, RS, Harvey, PD. Cognitive impairment in schizophrenia. Handb Exp Pharmacol. 2012; 213: 1137.CrossRefGoogle Scholar
5. Mohamed, S, Rosenheck, R, Swartz, M, Stroup, S, Lieberman, JA, Keefe, RSE. Relationship of cognition and psychopathology to function impairment in schizophrenia. Am J Psychiatry. 2008; 165(8): 978987.CrossRefGoogle Scholar
6. Lehoux, C, Gobeil, M-H, Lefèbvre, A-A, et al. The five-factor structure of the PANSS: A critical review of its consistency across studies. Clin Schizophr Related Psychoses. 2009; 3(2): 103110.CrossRefGoogle Scholar
7. Marder, SR, Davis, JM, Chouinard, G. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry. 1997; 58(12): 538546.CrossRefGoogle ScholarPubMed
8. Guy, W. Clinical Global Impressions. In: ECDEU Assessment Manual for Psychopharmacology. Washington, DC: Superintendent of Documents, US Government Printing Office, US Department of Health, Education, and Welfare Publication No. 76–338; 1976: 218222.Google Scholar
9. Meltzer, HY, Risinger, R, Nasrallah, HA, et al. A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia. J Clin Psychiatry. 2015; 76(8): 10851090.CrossRefGoogle ScholarPubMed
10. Aristada (aripiprazole lauroxil) extended-release injectable suspension, for intramuscular use [package insert]. Waltham, MA, USA: Alkermes Inc; Revised February 2017. http://aristada.com/hcp/ARISTADA-prescribing-information.pdf (accessed May 30, 2017).Google Scholar
11. Kane, JM, Carson, WH, Saha, AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002; 63(9): 763771.CrossRefGoogle ScholarPubMed
12. Kane, JM, Peters-Strickland, T, Baker, RA, et al. Aripiprazole once-monthly in the acute treatment of schizophrenia: findings from a 12-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014; 75(11): 12541260.CrossRefGoogle ScholarPubMed
13. Potkin, SG, Saha, AR, Kujawa, MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2003; 60(7): 681690.CrossRefGoogle ScholarPubMed
14. ABILIFY (Aripiprazole) Tablets, ABILIFY DISCMELT (Aripiprazole) Orally Disintegrating Tablets, ABILIFY (Aripiprazole) Oral Solution, ABILIFY (Aripiprazole) Injection for Intramuscular use Only. [Package insert]. Revised February 2017. https://www.otsuka-us.com/media/images/AbilifyPI_538.pdf (accessed May 30, 2017).Google Scholar
15. Citrome, L. The ABC’s of dopamine receptor partial agonists —aripiprazole, brexpiprazole and cariprazine: the 15-min challenge to sort these agents out. Int J Clin Pract. 2015; 69(11): 12111220.CrossRefGoogle ScholarPubMed
16. Citrome, L. Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil. Expert Rev Clin Pharmacol. 2016; 9(2): 169186.CrossRefGoogle ScholarPubMed
17. Fusar-Poli, P, Kempton, MJ, Rosenheck, RA. Efficacy and safety of second-generation long-acting injections in schizophrenia: a meta-analysis of randomized-controlled trials. Int Clin Psychopharmacol. 2013; 28(2): 5766.CrossRefGoogle ScholarPubMed

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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
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