FDA WARNING_LETTER - James Findling - August 02, 2019

The FDA issued a Warning Letter to Dr. Findling following an inspection from July 11 to August 2, 2019, regarding the conduct of clinical investigation Protocol (b)(4) for the investigational drug (b)(4). The inspection, part of the Bioresearch Monitoring Program, identified significant violations of 21 CFR 312.60, specifically the failure to ensure the investigation was conducted according to the investigational plan.

Key violations include: 1. **Randomization of Ineligible Subjects:** Two of three randomized subjects (Subjects (b)(4) and (b)(4)) were randomized into Study Period 3 despite having dose increases during Study Period 2, which violated eligibility criteria requiring a steady dose. The protocol mandated no dose increases above the therapeutic level established at the end of Study Period 1 for randomization. 2. **Failure to Discontinue Subjects with Elevated UFC Levels:** Two subjects (Subjects (b)(4) and (b)(4)) were not discontinued from randomized treatment during Study Period 3 despite multiple instances of elevated urine free cortisol (UFC) levels (> 1.5 times ULN for mean and at least two individual samples), as required by the protocol to minimize exposure to ineffective treatment.

The FDA found Dr. Findling's August 22, 2019, response to the Form FDA 483 inadequate, lacking sufficient detail on corrective actions