Dexmethylphenidate Hydrochloride (Page 6 of 8)

14 CLINICAL STUDIES

14.1 Pediatric Patients

A randomized, double-blind, placebo-controlled, parallel-group study (Study 1) was conducted in 103 pediatric patients (ages 6 to 12, n = 86; ages 13 to 17, n = 17) who met DSM-IV criteria for ADHD inattentive, hyperactive-impulsive or combined inattentive/hyperactive-impulsive subtypes (Study 1).

Patients were randomized to receive either a flexible-dose of dexmethylphenidate hydrochloride extended-release capsules (5 to 30 mg/day) or placebo once daily for 7 weeks. During the first 5 weeks of treatment, patients were titrated to their optimal dose and remained on this optimal dose for the last 2 weeks of the study without dose changes or interruption.

Signs and symptoms of ADHD were evaluated by comparing the mean change from baseline to endpoint for dexmethylphenidate hydrochloride extended-release capsules and placebo-treated patients using an intent-to-treat analysis of the primary efficacy outcome measure, the DSM-IV total subscale score of the Conners ADHD/DSM-IV Scales for teachers (CADS-T). The CADS-T includes the ADHD Index (12 items) and the DSM-IV total subscale (18 items, total score range: 0 to 54); the latter is divided into inattentive (9 items) and hyperactive-impulsive (9 items) subscales. Teachers assessed behavior observed during the school day by completing the CADS-T weekly. A decrease in the CADS-T DSM-IV total subscale score from baseline indicates improvement.

The CADS-T total scores showed a statistically significant treatment effect in favor of dexmethylphenidate hydrochloride extended-release capsules than placebo (Table 6). There were insufficient adolescents enrolled in this study to assess the efficacy for dexmethylphenidate hydrochloride extended-release capsules in the adolescent population. However, pharmacokinetic considerations and evidence of effectiveness of immediate-release dexmethylphenidate hydrochloride in adolescents support the effectiveness of dexmethylphenidate hydrochloride extended-release capsules in this population.

Table 6: Summary of Efficacy Results from ADHD Study in Pediatric Patients (6 to 17 years) (Study 1)

Study Number	Treatment Group	Primary Efficacy Measure: CADS-T Total Score
		Mean Baseline Score (SD)	LS Mean Change from Baseline (SE)	Placebo-subtracted Differencea (95% CI)
Study 1	Dexmethylphenidate hydrochloride extended-release capsules 5 to 30 mg/day (n = 52)	33.3 (9.18)	16.41 (1.8)	10.64 (5.38, 15.91)
	Placebo (n = 45)	34.9 (10.03)	5.77 (1.93)	—
Abbreviations: ADHD, attention deficit hyperactivity disorder; SD, standard deviation; SE, standard error; LS Mean, least-squares mean; CI, confidence interval, not adjusted for multiple comparisons.a Difference (drug minus placebo) in least-squares mean change from baseline.

In 2 additional cross-over studies (Studies 2 and 3) in pediatric patients ages 6 to 12 years, who received 20 mg dexmethylphenidate hydrochloride extended-release capsules or placebo, dexmethylphenidate hydrochloride extended-release capsules were found to have a statistically significant treatment effect versus placebo on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) rating scale total scores at all-time points after dosing in each study (0.5, 1, 3, 4, 5, 7, 9, 10, 11, and 12 hours in Study 2 and 1, 2, 4, 6, 8, 9, 10, 11, and 12 hours in the study 3). SKAMP is a validated 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting. A treatment effect was also observed 0.5 hours after administration of dexmethylphenidate hydrochloride extended-release capsules 20 mg in an additional study of ADHD patients ages 6 to 12 years.

14.2 Adult Patients

A randomized, double-blind, placebo-controlled, parallel-group (Study 4) was conducted in 221 adult patients ages 18 to 60 years who met DSM-IV criteria for ADHD inattentive, hyperactive-impulsive or combined inattentive/hyperactive-impulsive subtypes (Study 4).

Patients were randomized to receive either a fixed dose of dexmethylphenidate hydrochloride extended-release capsules (20, 30, or 40 mg/day) or placebo once daily for 5 weeks. Patients randomized to dexmethylphenidate hydrochloride extended-release capsules were initiated on a 10 mg/day starting dose and titrated in increments of 10 mg/week to the randomly assigned fixed dose. Patients were maintained on their fixed dose (20, 30, or 40 mg/day) for a minimum of 2 weeks.

Signs and symptoms of ADHD were evaluated by comparing the mean change from baseline to endpoint for dexmethylphenidate hydrochloride extended-release capsules and placebo-treated patients using an intent-to-treat analysis of the primary efficacy outcome measure, the investigator-administered DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS).

The DSM-IV ADHD-RS is an 18-item questionnaire with a score range of 0 to 54 points that measures the core symptoms of ADHD and includes both hyperactive/impulsive and inattentive subscales.

All 3 dexmethylphenidate hydrochloride extended-release capsule doses (20, 30, and 40 mg/day) showed a statistically significant treatment effect compared to placebo. There was no obvious increase in effectiveness with increasing the dose.

Table 7: Summary of Efficacy Results from ADHD Study in Adults (Study 4)

Study Number	Treatment Group	Primary Efficacy Measure: ADHD-RS Total Score
		Mean Baseline Score (SD)	LS Mean Change from Baseline (SE)	Placebo-subtracted Differencea (95% CI)
Study 4	Dexmethylphenidate hydrochloride extended-release capsules 20 mg/day (n = 57)	36.8 (7.2)	13.27 (1.44)	5.71 (1.64, 9.78)
	Dexmethylphenidate hydrochloride extended-release capsules 30 mg/day (n = 54)	36.9 (8.07)	12.86 (1.48)	5.31 (1.18, 9.44)
	Dexmethylphenidate hydrochloride extended-release capsules 40 mg/day (n = 54)	36.9 (8.25)	16.51 (1.48)	8.96 (4.83, 13.08)
	Placebo (n = 53)	37.5 (7.82)	7.55 (1.49)	—
Abbreviations: ADHD, attention deficit hyperactivity disorder; SD, standard deviation; SE, standard error; LS Mean, least-squares mean; CI, confidence interval, not adjusted for multiple comparisons.a Difference (drug minus placebo) in least-squares mean change from baseline.