On May 9, 2018, FDA issued draft guidance on Uncomplicated Urinary Tract Infections (uUTIs): Developing Drugs for Treatment. The guidance addresses the clinical development of drugs intended to specifically treat uUTIs.
FDA previously issued a separate guidance discussing complicated urinary tract infections (cUTIs), which are distinct from uUTIs. uUTIs, also referred to as acute cystitis, occur in females with normal anatomy of the urinary tract and are characterized by pyuria and a documented microbial pathogen on urine culture.
The guidance provides recommendations on the overall development program and clinical trial designs for drugs to support an indication for the treatment of uUTIs. To demonstrate efficacy, FDA recommends randomized, double-blind, controlled trials in female patients with uUTI, using a superiority or noninferiority design.
Additionally, FDA recommends that the intended trial population should be adult females, across a wide age range, with pyuria and at least two signs or symptoms of uUTI such as: dysuria, urinary frequency, urinary urgency, or suprapubic pain. FDA states that patients with signs or symptoms of systemic illness (e.g. fever greater than 38 degrees Celsius, shaking chills, etc.) or treatment with other effective antibacterial drugs for treatment of the current uUTI should be excluded.
Before patient receipt of drug therapy, the guidance recommends all patients to submit a urine specimen for culture and antimicrobial testing. The guidance states that development of new diagnostic tests may facilitate future clinical trial design and benefit patients by providing earlier diagnosis of causative organisms.
FDA recommends that the primary efficacy endpoint should be based on a responder outcome of clinical and microbiologic response. FDA also states that secondary endpoints will help to evaluate sustained microbiologic success and resolution of all clinical symptoms of uUTI.
Furthermore, FDA discusses developing a detailed statistical analysis plan using various analysis population in uUTI clinical trials such as: Intent-to-treat (ITT) population, the microbiological intent-to-treat (micro-ITT) population, clinically evaluable population, microbiologically evaluable population, and safety population. FDA recommends the micro-ITT population should be considered the primary analysis population for a noninferiority trial. FDA also gives recommendations of sample size for noninferiority trials and superiority trials.