FDA Clinical Inspection Summary: Verzenio (abemaciclib) submitted by Eli Lilly

FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary for Verzenio (abemaciclib) submitted by Eli Lilly. Six sites were selected for inspection, based on high site specific efficacy results, participation in numerous other trials, low numbers of protocol deviations, low numbers of reported Serious Adverse Events (SAEs) and low numbers of deaths on study. Inspections ranged from three days to three weeks. Two sites received FDA form 483s.

Dr. Dickler was cited for:

  • Failing to report adverse events to the sponsor, specifically five adverse events from three patients.
  • Failing to prepare and maintain adequate and accurate case histories.
    • Failing to report concomitant medications for four subjects. FDA notes that the monitor had informed the site at the start of the trial that recording this information was unnecessary. 
    • One adverse event did not have a toxicity grading.
    • The source for two concomitant medications was missing.

Dr. Salinas was cited for:

  • Failing to prepare and maintain adequate and accurate case histories.
    • FDA notes numerous discrepancies and only provides a few examples (three and a half pages) in the Clinical Inspection Summary.
    • For example, the radiology scan indicated a tumor was 10.6 mm, but the data listings indicated the tumor measured 100.6 and the source worksheet indicated a measurement of 106 mm.
    • Other examples include source worksheets indicated radiology scans were missed, but values for these scans were in the data listings.
    • Lesions had sizes of 4.9 mm in the data listings, but source worksheets indicated that they were too small to measure and data entry conventions stated that lesions too small to measure should have a value of 5.0 mm assigned.
    • Data listings indicated stable disease, the radiology report indicated progressive disease and the source worksheet had "None" entered for tumor response.
    • FDA notes that a sensitivity analysis should be performed, as the above listed errors impacted the primary endpoint for three patients at the site.


FDA Clinical Investigator Warning Letter (Phase 4 study)

FDA posted a warning letter to a Clinical Investigator this week for activities on a Phase 4 study of Chantix (varenicline) by Pfizer. Three FDA inspectors conducted the inspection, which lasted over one month. 

Dr. Curtis was warned for:

  • Failing to follow the investigational plan
    • Enrolling two subjects who did not smoke enough cigarettes per day
    • Enrolling one subject who did not meet enrollment criteria for amount of carbon monoxide exhaled at screening
    • Enrolling a subject who was taking prohibited concomitant medications
  • Failing to maintain adequate and accurate case histories
    • Failing to complete three summary score sheets to determine psychiatric symptoms, but entering a summary score into the electronic Case Report Form (CRF)
  • Failing to maintain adequate records of drug accountability
    • FDA compared drug amount dispensed versus amount returned versus the calculations of what should have been returned and compared it to the CRF entries

FDA notes that the Investigator's initial response to the 483 relied heavily on changes to institutional SOPs and did not account for any specific actions by the investigator to prevent issues in the future. FDA stated that this prevented them from determining the adequacy of the response.