Pilot Phase II study of mazindol in children with attention deficit/hyperactivity disorder

Abstract

Objective

Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its pharmacokinetics, short-term efficacy, and safety.

Subjects and methods

A total of 24 children (aged 9–12 years) with ADHD (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text-revision criteria) received a daily dose of 1 mg for 7 days and were followed for 3 additional weeks. Pharmacokinetic samples were collected after the first administration. ADHD symptoms were assessed using the ADHD Rating Scale (RS)-IV, Conners’ Parent Rating Scale – Revised: Long (CPRS-R:L) at screening, baseline, and the end of the study. The Clinical Global Impression – Severity (CGI-S) scale was assessed at baseline, and the CGI – Improvement (CGI-I) scale was assessed at subsequent visits.

Results

Twenty-one subjects (aged 10±1 years) were analyzed. Pharmacokinetic data were described by a one-compartment model with first-order absorption, elimination, and lag time. The typical apparent clearance and apparent volume of distribution were 27.9 L/h and 234 L, and increased with fat-free mass and age, respectively. The mean change in score in ADHD RS-IV after 1 week of mazindol was −24.1 (P<0.0001), greater than a 90% improvement from baseline. Reduction of CPRS-R:L and CGI-S scores were −52.1 (P<0.0001) and −2.5 (P<0.01), respectively. Adverse events were mild to moderate, decreased appetite and upper abdominal pain being the most common.

Conclusion

This preliminary study shows that mazindol might be an effective, well-tolerated, and long-acting (more than 8 hours) agent for the treatment of ADHD in children.

Keywords:

• pharmacokinetics
• efficacy
• safety
• mazindol
• ADHD
• pediatrics

Acknowledgments

This study was supported by a grant from Assistance Publique – Hôpitaux de Paris (APHP). Genopharm helped to support this study and provided the tablets of mazindol. The authors wish to thank the nurses, technicians, and statisticians involved in this study. The authors also wish to thank Ms Delphine Prieur (assistant) and Dr Florence Tubach (URC Bichat), who contributed to the study design and methodology, and MedEdGlobal Solutions France. Preliminary results of this study were presented at the 56th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, October 27–November 1, Honolulu, HI, and at NeuroTalk, June 25–28, 2010, Singapore.

Disclosure

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author). EK has served on advisory boards for Shire Pharmaceuticals and Vifor. He has consulted for Shire Pharmaceuticals. He has served as a medical writer for Remidica. He has served on the speaker’s bureau of UCB and served as a principal investigator in clinical trials supported by Eli Lilly and Janssen-Cilag, and has been a coinvestigator in studies sponsored by GlaxoSmithKline, Cephalon, Eli Lilly, and Shire Pharmaceuticals. He serves as a consultant for Shire Pharmaceuticals, BLK Pharma, and Vifor. EK is the inventor of the mazindol combination in the treatment of ADHD (WO/2007/116076). The other authors report no conflicts of interest in this work.