The FDA has provided a revised version of the draft guidance on trial designs and endpoints for clinical evaluation of gastroparesis. medication.
The updates concern the agency’s initial guidance on gastroparesis trials issued in July 2015.
“Changes from the previous draft reflect FDA’s current thinking on the development of clinical outcome assessment measures and statistical considerations for use of those measures to assess primary and secondary efficacy endpoints of clinical trials for gastroparesis,” according to a release issued by the FDA.
As in the initial guidance, the FDA wrote that although reliable patient-reported outcomes (PRO) would be the ideal efficacy-assessment tool in clinical trials for drugs targeting gastroparesis, none currently exist. However, the FDA included some guidance on how trial sponsors could include these measurements.
“Sponsors may wish to include and evaluate well-defined PRO instruments assessing the relevant important signs and symptoms in early drug development — and evaluate the results in dose-ranging phase 2 trials or stand-alone noninterventional studies — to support their future use in phase 3 trials,” the FDA wrote. “We encourage early and regular discussions with FDA regarding the development of these PRO instruments.”
According to the draft guidance, trials for gastroparesis drugs should consist of a randomized, double-blind, placebo-controlled trial and include a 1- to 2-week screening period followed by a baseline assessment of at least 7 days. The primary endpoint should measure the change in signs and symptoms from baseline over a treatment period of at least 12 weeks, and the endpoint should be assessed based on patients’ daily reporting to avoid errors in recall.
Although patients with idiopathic and diabetic gastroparesis share the same typical signs and symptoms, the FDA says these patients should be studied in separate clinical trials.
The FDA recommends that five core symptoms of gastroparesis — nausea, vomiting, postprandial fullness, early satiety and abdominal pain — should be used as endpoints in clinical trials. These symptoms, other than vomiting, should also be rated by severity, according to the FDA.
The agency also advised that an adequate number of assessments are needed to evaluate daily diary assessments created during the trial. If a clinical trial uses a weekly summary score, the FDA wrote that the sponsor should be able to provide assessments from at least 4 of the 7 days.
“We recommend that sponsors analyze the primary and secondary endpoints as continuous or ordinal variables; we do not recommend the use of percentage change,” the FDA wrote. “In general, a traditional responder analysis would not be appropriate unless the targeted response is complete resolution of signs and symptoms. In addition, we encourage the use of baseline values and other covariates to improve the efficiency of primary and secondary endpoint analyses.”
The FDA is accepting public comments and suggestions on the draft guidance for 60 days. Ultimately, the agency hopes the new guidance will “provide a path forward” for development of gastroparesis drugs.
Reference: HHS/FDA/Center for Drug Evaluation and Research. Gastroparesis: Clinical Evaluation of Drugs for Treatment. Guidance for Industry. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/gastroparesis-clinical-evaluation-drugs-treatment-guidance-industry