Food and Drug Administration

Center for Drug Evaluation and Research

Holiday Inn, 8777 Georgia Ave., Silver Spring, MD

This report contains public information that has not been reviewed by the agency or AntiInfective Drugs Advisory Committee. The official summary minutes will be prepared, circulated, and certified as usual. Transcripts will be available in about 12 days. External requests should be submitted to the Freedom of Information office.

The AntiInfective Drugs Advisory Committee of the Food and Drug Administration, Center for Drug Evaluation and Research met on November 7, 2001 at the Holiday Inn, 8777 Georgia Ave., Silver Spring, MD 20910.

The committee considered the safety and efficacy of 1-day and 3-day dosing regimens of

azithromycin suspension (New Drug Application 50-710, Pfizer Inc.) for the treatment of otitis media. The Committee had received a briefing document from the FDA and a background document from Pfizer.

There were approximately 150 persons present at the meeting. The meeting was called to order at 8:15 am. by the Chair, Barth Reller, M.D. Thomas H. Perez, Executive Secretary of the AntiInfective Drugs Advisory Committee read the Meeting Statement. The Committee members and discussants introduced themselves. Janice Soreth, Acting Director, Division of Anti-Infective Drug Products, presented retiring members of the committee, Dr. Joan P. Chesney, and Dr. Celia Christie-Samuels, M.D., with a plaque to recognize them for their four years of service and contributions to the Food and Drug Administration. Dr. Soreth then provided opening comments.

At 8:25 Colin Marchant, M.D., guest consultant for the FDA, began his presentation.

At approximately 9:00, representatives of Pfizer began the sponsor’s presentation including the following topics and presenters:

FDA’s presentation began at 10:55 and included the following topic and presenter:

The Open Public Hearing portion of the meeting began at 11:20 with the following two participants, each providing a presentation.

Dr. Janice Soreth, at 1:25 p.m. described the charge to the Committee as a prelude to the discussion and vote section of the meeting. The Committee continued with a discussion of the questions and vote provided below. The voting concluded at 2:35.

The meeting continued with the following presentation.

After a thorough discussion of the topic was held that focussed on lessons learned from this and previous meetings dealing with this issue, the meeting was adjourned at 4:45 p.m.

1. Do the data support the safety and efficacy of a single dose (30 mg/kg) and/or of the three-day regimen (10 mg/kg/day for 3 days) of azithromycin for the treatment of AOM?

1. If yes, should any caveats be included in the label based on the results of the studies with tympanocentesis at baseline (single-tap)?

The committee member’s responses to question 1 and its subparts provided many comments qualifying their votes ranging from no caveats to more PK/PD and bacteriologic studies particularly in children less than two years of age. The complete details of the responses are recorded on the meeting transcripts to which those interested are referred.

2. If no, what additional study (-ies) do you recommend?

1. If approval of the single-dose regimen is recommended, what advice should be given to prescribers and patients regarding the increased vomiting associated with the use of this regimen?

Clinical Trials Issues

1. Should clinical-only trials continue, or should all enrolled patients have a tympanocentesis at baseline?
2. Should non-comparative microbiology studies continue?
3. Should guidance incorporate stratification by age (< 2 years)? If so, what proportion of patients should be under the age of 2 years?

In your discussion, please comment on the merits of studies with clinical information only, studies with tympanocentesis, ideal timing of clinical assessments (end-of-therapy v. later follow-up), and alternative study designs (comparative trials with microbiology, double-tap studies, placebo-controlled studies with early escape).