Insufficient Evidence of Clinically Meaningful Benefit and Unfavorable Risk-Benefit Profile
Severity: criticalThe agency determined that there is insufficient evidence to conclude that the effect of Nocdurna relative to placebo on the number of nocturnal voids in adults with nocturia due to nocturnal polyuria is clinically meaningful and outweighs the risks of hyponatremia associated with the drug's use. This conclusion was reached after considering the submitted information and discussions at an advisory committee meeting.
Recommended response: Conduct a new clinical trial to demonstrate meaningful clinical benefit, employing validated patient-reported outcome instruments that capture the clinical impact of changes in nocturnal voids. Prospectively evaluate hyponatremia monitoring strategies for mitigating risk in the postmarketing setting. Include these strategies in the Complete Response.
Prescribing Information Not Yet Reviewed
Severity: minorThe agency reserves comment on the proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review the PLR Requirements for Prescribing Information website, including regulations and related guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist. Any revised labeling must conform to format items in regulations and guidances and include updated content of labeling in Structured Product Labeling (SPL) format.
Recommended response: Review PLR requirements, SRPI checklist, and relevant guidances. Revise labeling to conform to format items and submit updated content in SPL format once clinical deficiencies are addressed.
Cited: 21 CFR 314.50(l)(1)(i)
Proprietary Name Resubmission Required
Severity: infoThe proposed proprietary name, Nocdurna, 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 with the complete response to the application deficiencies.
Comprehensive Safety Update Required
Severity: majorA comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b). This includes detailing significant changes in the safety profile, incorporating new safety data from all nonclinical and clinical studies/trials (regardless of indication, dosage form, or dose level), presenting tabulations of new and combined data, comparing frequencies of adverse events, providing separate tables for other indications, retabulating reasons for premature discontinuation, providing case report forms and narrative summaries for deaths/serious adverse events, describing changes in common adverse events, providing updated exposure information, summarizing worldwide safety experience, and providing English translations of current approved foreign labeling.
Recommended response: Compile a comprehensive safety update including all new nonclinical and clinical data, adverse event frequencies, patient narratives for deaths/serious AEs, updated exposure, worldwide experience, and foreign labeling translations, as per 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
