Regulatory Focus™ > News Articles > New FDA Guidance on Sinus Infections Focuses on Design of Clinical Trials

New FDA Guidance on Sinus Infections Focuses on Design of Clinical Trials

Posted 05 October 2012 | By Alexander Gaffney, RAC 

A new guidance document released by the US Food and Drug Administration (FDA) aims to assist sponsors with the development of pharmaceutical products for the treatment of acute bacterial sinusitis (ABS), more commonly known as a sinus infection.

The guidance is particularly focused on two aspects of development: the overall development program and the design of clinical trials used to show safety and efficacy. It does not address drugs used to prevent ABS from occurring or drugs used to treat acute non-bacterial sinusitis.

FDA goes on to say that development programs should generate nonclinical data documenting the drug's effectiveness versus the three most common bacterial pathogens responsible for ABS: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Animal models may also be useful for understanding and predicting pathological and histological responses, though FDA cautioned they are no substitute for studies in humans.

When it comes to clinical trials, FDA said it only recommends superiority trials-not non-inferiority trials-because it is unable to establish benefit benchmarks using data from existing ABS trials. The total number of trials to be conducted will depend on the overall development plan, but FDA said a single trial may be adequate if there are data from other clinical trials to support the trial and pharmacokinetic and pharmacodynamics studies also show clear evidence of efficacy.

Because the course of treatment for sinus infections is relatively short, FDA said it anticipates direct measurements of treatment efficacy will be used. Surrogate endpoints will not be accepted. Drugs with "clinically significant toxicity" should also be avoided unless the sponsor can show their benefits outweigh their risks in a clinically meaningful subpopulation of patients, added FDA.

The guidance goes on to list the specific signs and symptoms associated with ABS, as well as conditions that should cause them to exclude patients from participation, including patients with symptoms exceeding four weeks, patients with cystic fibrosis, immunocompromised patients or ones with nasal polyposis.

All patients being enrolled into a clinical trial should be tested for the presence of ABS, and FDA recommends the use of radiological assessment to "enrich the trial population" as well.

FDA said it will determine an effective treatment to be one which achieves improvement or resolution of symptoms without the introduction of new complications. Clinical failure will occur if a treatment does not achieve improvement in patients within 72 hours, allows for new symptoms to develop or allows new complications to develop. FDA said it also will not accept data from patients if they are found to have been using other antimicrobial medications.

Efficacy can be measured using a scale-based score, but FDA said it recommends that the primary efficacy endpoint be seen as the time until symptoms improve or until the infection is gone.

Read more:

FDA - Guidance for Industry Acute Bacterial Sinusitis: Developing Drugs for Treatment

Federal Register - Guidance for Industry; Availability: Acute Bacterial Sinusitis; Developing Drugs for Treatment


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