28 Days Later: FDA's Clinical Endpoint to Stop the Horror of Complicated Abdominal Infections

Regulatory News

New guidance issued by the US Food and Drug Administration (FDA) is intended to make it easier for pharmaceutical companies to develop drugs to treat "complicated" intra-abdominal infections (cIAIs), with a goal of achieving a successful outcome within 28 days of a patient starting treatment.

Thinking About Development Questions

The final guidance document, Complicated Intra-Abdominal Infections: Developing Drugs for Treatment, is an update to a 2012 draft guidance by the same name and meant to answer a common question in drug development: What information would a company need to collect to indicate that its product is safe and effective?

FDA's guidance contains several answers to this question as it relates specifically to cIAIs—a common type of infection which can result in severe sepsis and death.

New drug application sponsors can use data from either a non-inferiority trial—a trial showing a drug is no worse than the next best competitor—or a superiority trial, which indicates that a product is better than the current standard of treatment.

As is standard practice, trials should be randomized, double-blind and "active-controlled" using a standard of care, FDA said. "Placebo-controlled trials are not appropriate for this indication," FDA noted.

FDA also explains that some patients will not be allowed to participate in the trial, such as those patients who have received antibacterial drug therapy for 24 of the 72 hours preceding the start of the trial. This is meant to ensure that the observed effect in the new trial is due to the new drug, and not the lingering effects of another drug.

Sponsors will need to take a microbiologic sample from each patient to confirm that each patient is in fact affected by the bacteria the drug is intended to treat. This may also help companies to identify additional strains which might be positively affected by the drug, FDA's guidance adds.

Clinical Endpoint: 28 Days

Perhaps most importantly, FDA has maintained a clinical endpoint established in its draft guidance document. "The primary endpoint of clinical success is defined as resolution of the baseline signs and symptoms of cIAI based on objective assessments of events from randomization until approximately day 28 [of the trial]," FDA writes in the guidance.

Clinical "failure" would occur if the patient died, became infected, required unplanned surgery or required additional antibacterial drug therapy, FDA explained.

Complicated Intra-Abdominal Infections: Developing Drugs for Treatment (FR)