FDA issues draft guidance on clinical evaluation of gastroparesis drugs
The FDA has issued a draft guidance on trial designs and endpoints for clinical evaluation of gastroparesis drugs.
“The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of diabetic and idiopathic gastroparesis,” the FDA wrote in the draft guidance. “Specifically, this guidance addresses the [FDA’s] current thinking regarding clinical trial designs and clinical endpoint assessments to support development of gastroparesis drugs,” for which there is an “urgent medical need.”
While a “well-defined and reliable” patient-reported outcome (PRO) instrument would be the ideal primary efficacy assessment tool for gastroparesis drug trials, one is not currently available, and until that time the FDA said sponsors should consider the following recommendations regarding trial design, populations, outcome assessment measures and endpoints.
Trials should be designed as randomized, double-blind, placebo-controlled studies with a 1- to 2-week screening period, a longer than 1-week baseline assessment period, a longer than 12-week treatment period and a 2- to 4-week randomized withdrawal period. A 12-month placebo-controlled safety study should also be performed before submission of a new drug application.
Separate clinical trials should be performed for patients with idiopathic and diabetic gastroparesis “to fully describe safety and efficacy in each group.”
Trial populations should be clinically diagnosed based on history of symptoms, exclusion of other etiologies and delayed gastric emptying. They should also have moderate-to-severe symptoms, should not be on opioids, and patients with diabetic gastroparesis should have “controlled and stable blood glucose levels.”
The primary endpoint should be assessed based on daily patient-reporting to measure changes from baseline in the “five core signs and symptoms:” nausea, vomiting, early satiety, abdominal pain, and postprandial fullness. “All five should be measured, even in trials where a drug is intended to treat only a subset of the core signs/symptoms, to ensure that treatment does not worsen the remaining signs/symptoms,” according to the FDA. Because it does not correlate with changes in these core symptoms, gastric emptying time should not be used as a primary efficacy endpoint, but can be used as a secondary endpoint.
“The proposed endpoints and trial design recommendations in this guidance are considered appropriate for use in the evaluation of drugs for the treatment of idiopathic and diabetic gastroparesis,” the FDA wrote. “These recommendations can assist companies in developing treatments to address the needs of patients with gastroparesis while the important work of developing well-defined and reliable PRO instruments for clinical trials of gastroparesis continues.”
There will be a 60-day period for public comment on the draft guidance following its release on July 22, after which time the agency will look to finalizing its recommendations.
HHS/FDA/Center for Drug Evaluation and Research. Gastroparesis: Clinical evaluation of drugs for treatment. Guidance for industry. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM455645.pdf. Accessed July 23, 2015.