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Symptomatic Nonerosive Gastroesophageal Reflux Disease: Developing Drugs for Treatment: Draft Guidance for Industry

DraftCenter for Drug Evaluation and Research09/17/2025

Description

The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a draft guidance for industry entitled “Symptomatic Nonerosive Gastroesophageal Reflux Disease: Developing Drugs for Treatment.” The draft guidance details FDA’s recommendations on the clinical trials for drugs being developed for the treatment of symptomatic nonerosive gastroesophageal reflux disease (sGERD) in adults, including considerations for eligibility criteria, trial design features, efficacy evaluations, and safety assessments.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

1
Therapeutic biological products

Licensed under section 351 of the Public Health Service Act.

Stakeholders

1
Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

2
Randomized, double-blind, placebo-controlled trial

Recommended trial design for sGERD drugs

Clinical trials

Development program for drugs intended for sGERD treatment

Document Types

1
Patient-reported outcome measure

Instrument used to assess symptoms like heartburn and regurgitation

Attributes

2
Type I error rate

Statistical parameter requiring strong control when testing multiple endpoints

Inclusion Criteria

Requirements for enrolling subjects in sGERD trials

Technical Details

Substances

5
New molecular entity

Drug type that may alter the minimum acceptable size of the safety database

Tricyclic antidepressants

Drugs with significant anticholinergic effects

Histamine H2-receptor antagonists

Acid-reducing medications

Proton pump inhibitors

Acid-reducing medications generally not permitted as concomitant use

Helicobacter pylori

Subjects testing positive for this during screening should be excluded

Testing Methods

2
Endoscopy

Method used to document healed EE and assess primary endpoints

Endoscopic evaluation

Used to define EE by the presence of superficial esophageal erosions.

Clinical Concepts

6
Eosinophilic esophagitis

Coexisting disease affecting the esophagus

Zollinger-Ellison syndrome

Pathological hypersecretory condition excluded from guidance

Barrett's esophagus

Potential progression from untreated erosive esophagitis.; Exclusion criterion for the trial

Erosive esophagitis

Condition excluded from the scope of this specific guidance

Heartburn

Primary symptom and inclusion criterion for sGERD trials

Symptomatic nonerosive gastroesophageal reflux disease

Target disease for drug development guidance

Identified Hazards

Hazards

2
Osteoporosis-related bone fractures

Potential risk identified with long-term acid suppression

Clostridioides difficile enteric infections

Potential risk identified with long-term acid suppression

Standards & References

Specifications

1
Heartburn-free days

Primary efficacy endpoint defined as a 24-hour period with no heartburn

ICH References (1)

ICH E9(R1)

Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Symptomatic Nonerosive Gastroesophageal Reflux Disease: Developing Drugs for Treatment: Draft Guidance for Industry | Guideline Explorer | BioRegHub