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A Post Hoc Analysis of d-threo-Methylphenidate Hydrochloride (Focalin) Versus d,l-threo-Methylphenidate Hydrochloride (Ritalin)

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ABSTRACT

Objective:

To evaluate clinical measures of the benefit/risk ratio in a post hoc analysis of a clinical trial of d-threo-methylphenidate hydrochloride (d-MPH) and d,l-threo-methylphenidate hydrochloride (d,l-MPH).

Method:

Data from a phase III clinical trial was used to compare equimolar doses of d-MPH and d,l-MPH treatment for attention-deficit/hyperactivity disorder (ADHD) on clinician ratings of improvement/deterioration, teacher ratings of remission, and duration of action.

Results:

d-MPH was clinically and statistically significantly superior to d,l-MPH on clinician's dimensional ratings of global improvement, teacher ratings of remission of ADHD symptoms and parent 6:00 p.m. ADHD symptom ratings. No treatment differences were observed for symptom ratings at 3:00 p.m. and for 6:00 p.m. math test performance.

Conclusion:

The results suggest that the two drugs may have distinct profiles on the measures analyzed. Because d-MPH may have be more than twice the potency of d,l-MPH, the differences reported here are only applicable to the doses of the study drugs involved in the clinical trial. The results are limited by the exploratory nature of our analysis, small samples, and multiple analyses. The findings are suggestive that further study is warranted to look at these differences prospectively but cannot be used to draw clinical conclusions at this time.

Section snippets

METHOD

Full details of the clinical trial design can be found in the original study report (Wigal et al., 2004). We discuss those aspects of the methodology that are relevant to the analysis reported here. Because this study involves a post hoc analysis of data presented by other investigators, the primary methodology lies in our selection of measures and choice of statistical analysis.

Clinician Ratings

Summary data are presented in Table 1. Direct comparison of end point mean CGI-I scores between d-MPH and d,l-MPH showed a significant difference between the two active treatments with d-MPH superiority, t(1,87) = 2.39, p = .019. Analysis of the proportion of treatment responders based on CGI-I ratings of “much improved” and “very much improved” favored d-MPH, but the difference was not significant (χ21 = 3.346, p = .067).

Of patients who received d,l-MPH, 11.1% deteriorated in treatment (rated

DISCUSSION

For the doses used within the study design and for this post hoc analysis, d-MPH was statistically significantly superior to d,l-MPH on clinician ratings of overall improvement, teacher ratings of the percentage of children achieving full remission, and parent ratings of ADHD symptoms at 6:00 p.m. Child performance on the math test done 6 hours post-dose did not differ between the two treatments. Of the patients on d,l-MPH, 11.1% deteriorated and none on d-MPH did, a difference that was not

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    Dexmethylphenidate HCl (d-MPH, Focalin®, Celgene Corp., Summit, NJ, the d-isomer of d,l-threo-methylphenidate [d,l-MPH]), the product used in this study, has been approved in the United States for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents, and a once-a-day formulation of d-MPH (Focalin XR®) has been approved in the United States for the treatment of ADHD in children, adolescents, and adults. Both the pharmacological properties12–15 and the clinical efficacy16 of d,l-MPH reside in both the d and l enantiomers and, therefore, d-MPH is efficacious at roughly half the dose of d,l-MPH.17 No adverse events (AEs) unique to chirally pure d-MPH have been reported.18

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This study was supported by Celgene Corporation.

Disclosure: Current industry financial relationships for Dr. Weiss are as follows: consultant, advisory board, speakers’ bureau and research contracts with Eli Lilly and Janssen Ortho; consultant, advisory board, and speakers’ bureau with Shire; consultant with Johnson & Johnson and Purdue Pharma; research contract with Circa Dia BV. Dr. Weiss has received payment for consultation and work as a clinical investigator from Celgene Corporation and Novartis Corporation. Mr. Patin is a full-time employee of Celgene Corporation and owner of stock through employment options.

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