Unacceptable Rate of Insomnia in Pediatric Population
Severity: criticalPhase 3 studies (Study 108) showed a significantly higher rate of insomnia (33% in HLD 200 group vs. 9% placebo; 43% in children ages 6 to 9) compared to other approved methylphenidate products (2-13%). Adjusting the timing of the evening dose did not appear to mitigate this risk. This indicates an unfavorable benefit-risk profile for the proposed pediatric population at the tested doses.
Recommended response: Conduct an additional double-blind, placebo-controlled, fixed-dose study in children ages 6 to 12 years to identify a safe and effective lower dose. Consider an additional study in adolescents ages 13 to 17 years if a favorable benefit-risk profile cannot be achieved in children.
Inadequate Prescribing Information Content and Format
Severity: majorThe agency reserves comment on the proposed labeling until the application is otherwise adequate. However, it requires updated content of labeling in Structured Product Labeling (SPL) format, conforming to PLR requirements and guidance documents.
Recommended response: Review the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites, including regulations and related guidance documents. Use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure that the prescribing information conforms with format items in regulations and guidances. Update content of labeling in SPL format.
Cited: 21 CFR 314.50(l)(1)(i)
Resubmission of Proprietary Name Required
Severity: minorThe proposed proprietary name, Jornay PM, was found acceptable pending approval of the application in the current review cycle. It must be resubmitted when responding to the application deficiencies.
Recommended response: Resubmit the proposed proprietary name along with the complete response to the application deficiencies.
Comprehensive Safety Update Submission Required
Severity: majorA comprehensive safety update is required, including: detailed description of significant changes/findings in the safety profile; presentation of new safety data from studies/clinical trials for the proposed indication (using the same format as the original submission); tabulations of new safety data combined with original application data; tables comparing frequencies of adverse events; separate tables for adverse events in other indications; retabulation of reasons for premature trial discontinuation; case report forms and narrative summaries for deaths/serious adverse events; information on substantial changes in common adverse events; updated exposure information for clinical studies/trials; a summary of worldwide experience on the safety of this drug (including an updated estimate of use for drug marketed in other countries); and English translations of current approved foreign labeling not previously submitted.
Recommended response: Provide a detailed and comprehensive safety update as described in 21 CFR 314.50(d)(5)(vi)(b), incorporating all new nonclinical and clinical data, retabulations, narratives, exposure information, worldwide experience, and foreign labeling translations.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
