Regulatory Focus™ > News Articles > 2019 > 12 > FDA Drafts Recommendations for IC/BSP Drug Development

FDA Drafts Recommendations for IC/BSP Drug Development

Posted 04 December 2019 | By Michael Mezher 

FDA Drafts Recommendations for IC/BSP Drug Development

The US Food and Drug Administration (FDA) on Wednesday issued draft guidance providing recommendations for the clinical development of new drugs to treat patients with interstitial cystitis/bladder pain syndrome (IC/BPS).
 
According to FDA, “IC/BPS is a complex, poorly understood syndrome of unknown etiology,” that is diagnosed based on symptoms including chronic bladder pain or discomfort and frequent urination or nocturia and the exclusion of other conditions with similar symptoms.
 
FDA says the five-page draft guidance incorporates recommendations made during a 2017 meeting of the agency’s Bone, Reproductive and Urologic Drugs Advisory Committee that sought to gather input from the committee and drugmakers on how to approach clinical development.
 
Draft Guidance
 
The draft guidance itself provides recommendations for clinical trial enrollment criteria and endpoint selection, as well as other clinical trial design considerations.
 
FDA says that sponsors will generally need to conduct two six-month randomized, double-blind, placebo-controlled trials to demonstrate efficacy for new drugs to treat IC/BPS.
 
When it comes to enrolling patients in clinical trials for drugs to treat IC/BPS, FDA says sponsors should select patients who have had bladder pain/discomfort and at least one lower urinary tract symptom, such as urinary frequency, urgency or nocturia, for at least six months prior to enrollment.
 
FDA recommends that patients have a cystoscopy to rule out other conditions but notes that “patients are not required to have Hunner’s lesions on bladder cystoscopy.” If sponsors wish to include Hunner’s lesions as an inclusion criteria, FDA says that the “baseline appearance of the bladder pathology should be documented in a standardized fashion during screening,” and that sponsors should discuss their approach with the Division of Bone, Reproductive, and Urologic Products, “particularly for multinational trials,” as Hunner’s lesions are not common in the US.
 
The agency also encourages sponsors to enroll patients who have received prior treatment for IC/BPS “to improve generalizability of the results unless a compelling effectiveness or safety reason exists for excluding them.”
 
For effectiveness endpoints, FDA says that treatments should ideally improve both bladder and accompanying lower urinary tract symptoms. The guidance describes multiple approaches to evaluate patients’ symptoms, including change from baseline for patients’ self-identified most bothersome symptom for both bladder pain/discomfort and lower urinary tract symptoms or a single primary effectiveness endpoint if the drug is not expected to improve lower urinary tract symptoms.
 
While FDA acknowledges that it is “not aware of any specific [patient reported outcome] PRO instruments that are adequate for regulatory use to assess symptomatic improvements in IC/BPS,” it encourages sponsors to seek input on potential PRO measures, and says sponsors may pilot PRO instruments in Phase II trials.
 
Sponsors looking to evaluate Hunner’s lesions are instructed to contact the agency to discuss their approach as “results of posttreatment cystoscopy may or may not provide additional support for the effectiveness of the drug.”
 
Additionally, FDA says that sponsors should prespecify how they will define symptomatic flares and how the use of rescue medications will be accounted for in the efficacy analyses.
 
FDA

Regulatory Focus newsletters

All the biggest regulatory news and happenings.

Subscribe