Regulatory Decision Summary for Jornay PM

The purpose of this New Drug Submission was to obtain market authorization for Jornay PM (methylphenidate hydrochloride), filed by Ironshore Pharmaceuticals & Development Inc. Jornay PM presented as 20 milligram (mg), 40 mg, 60 mg, 80 mg, and 100 mg extended-release capsules for oral administration at bedtime for an effect the day after. Jornay PM was intended for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older.

Upon review of the submitted data package, Health Canada limited the indication to the younger age group and authorized Jornay PM for the treatment of ADHD in children (6-12 years of age).

Methylphenidate is a well-known drug product used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). This New Drug Submission (NDS) is to seek approval of a new delayed-release and extended-release capsule formulation of methylphenidate, Jornay PM, for administration at bedtime.

The sponsor’s clinical development program evaluated the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of Jornay PM across 10 clinical trials. The marketing authorization of Jornay PM was mainly supported by two adequate, well-controlled, Phase 3, efficacy and safety studies in pediatric ADHD subjects (aged 6 through 12 years) (Studies HLD200-107 and HLD200-108). The sponsor also submitted several Phase 1 PK and/or comparative bioavailability studies in an attempt to support efficacy and safety in adolescents and adults with ADHD.

The Phase 3 studies HLD200-107 and HLD200-108 are considered the pivotal efficacy studies and are the basis of this NDS. The primary efficacy objective for these studies was to demonstrate that evening treatment with Jornay PM improved control of ADHD symptoms, compared with placebo, throughout the day in pediatric subjects with ADHD. Overall, the data show that Jornay PM treatment was significantly more effective than placebo for the control of ADHD symptoms during the early morning and throughout the day as assessed by the Swanson, Kotkin, Agler, M-Flynn and Pelham Rating Scale combined scores (SKAMP CS), the ADHD Rating Scale based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (ADHD-RS-IV). The main/key secondary endpoints BSFQ (Before-School Functioning Questionnaire) and the PREMB-R AM (Parent Rating of Evening and Morning Behavior – Revised [completed by investigator based on parent interview], morning subscale) were supportive of the primary objectives.

For Study HLD200-107, as detailed in two independent investigations commissioned by the Sponsor, the results from Site 10 were excluded in a post hoc analysis of the dataset and were determined to be unreliable by the independent investigators. It was decided that since results from post hoc efficacy analyses remain supportive of efficacy results from the intent to treat (ITT) population (including all sites), it was acceptable to state efficacy results from all the sites in the product label. The approach to validate and support claims using a post-hoc analysis of the dataset in this instance is consistent with evaluations performed by other regulators, including the United States Food and Drug Administration.

The clinical program evaluating treatment of ADHD with Jornay PM included a total of 417 subjects, of whom 315 received the to-be-marketed formulation. In the Phase 3 classroom study HLD200-107, 96.3% of subjects treated with Jornay PM were exposed for at least 36 to more than 43 days, and the mean average daily dose was 49.8 milligrams (mg). In the Phase 3 Study HLD200-108, the majority (70.4%) of subjects treated with Jornay PM were exposed for 15 to 21 days, and the mean average daily dose was 52.1 mg.

The evaluation of safety of Jornay PM is based on the studies that had used the marketed formulation: two Phase 3 studies in pediatric subjects (aged 6 through 12 years), and the six Phase 1 studies in healthy adult volunteers. The analyses of safety show that Jornay PM is generally safe and well tolerated at all dose levels evaluated in studies of patients with ADHD. Overall, the types and frequencies of adverse events (AEs) observed in the clinical studies were like those described for other methylphenidate products. No new types or patterns of AEs were observed that were attributable to Jornay PM.

Based on the efficacy evidence limited to only children, a restricted indication to children aged 6 to 12 years old was granted, and the Product Monograph was updated accordingly and approved.

Overall, the benefit-harm-uncertainty profile was favourable for Jornay PM (20 mg, 40 mg, 60 mg, 80 mg, and 100 mg delayed-release and extended-release capsules) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance was recommended.

For further details about Jornay PM, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.