Anti-Infective Drugs Advisory Committee

Food and Drug Administration

Center for Drug Evaluation and Research

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

####### Summary Minutes of the November 7, 2001 Meeting Discussing

**"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.*"***

## **Members Present Consultants**

L. Barth Reller, M.D. Richard Gorman, M.D

Alan S. Cross, M.D. Mary Glode, M.D.

Joan P. Chesney, M.D.

Celia Christie‑Samuels, M.D.

Steve Ebert, Pharm, D.

Judith O\'Fallon, Ph.D.

James E. Leggett, Jr., M.D.

Ellen R. Wald, M.D.

###### FDA Participants

Mark Goldberger, M.D.

Janice Soreth, M.D.

Nasim Moledina, Ph.D.

John Alexander, M.D.

These summary minutes for the November 7, 2001 meeting of the
AntiInfective Drugs Advisory Committee were approved on November 16,
2001.

I certify that I attended the November 7, 2001 meeting of the
AntiInfective Drugs Advisory Committee and that these minutes accurately
reflect what transpired.

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Thomas H. Perez, M.P.H., R.Ph. L. Barth Reller, M.D.

Executive Secretary Chair

> 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.

> **Design of Clinical Trials of Antibiotic Therapy for AOM**

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

> **Azithromycin in the Treatment of Acute Otitis Media** - Michael W.
> Dunne, M.D., Vice President, Clinical Development, Infectious
> Diseases, Pfizer Global Research & Development

**The Bacterial Pathogenesis of Acute Otitis Me**dia - Edward J.
O\'Rourke, M.D., Professor of Pediatrics, Harvard Medical School

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

> **Azithromycin for AOM --** Nasim Moledina, M.D., Division of
> Anti-Infective Drug Products

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

> Michael R. Jacobs, M.D., Professor of Pathology, Case Western Reserve
> University
>
> Ron Dagan, M.D., Director, Pediatric Infectious Disease Unit, Soroka
> Medical Center

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.

> **Clinical Trials of AOM** - John Alexander, M.D., Division of
> Anti-Infective Drug Products

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.

**Questions for the Advisory Committee (11/7/01)**

**Product-Specific Questions**

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?

> **Vote: Single Dose - - - - - - Yes 6 No 4**

**Vote: *3 Day Regimen - - -* *Yes 7 No 3***

In your discussion, please comment on the significance of the following
and how they contributed to your recommendation: interpretation of the
data from clinical-only studies, studies with tympanocentesis at
baseline (single-tap), the natural history of the infection, and
information from the published literature.

a)  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.**

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

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2.  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

3\. Current guidance for AOM trial designs suggests one clinical-only
study and one single-tap study (which may be non-comparative). Please
discuss the following issues

a)  Should clinical-only trials continue, or should all enrolled
    patients have a tympanocentesis at baseline?

b)  Should non-comparative microbiology studies continue?

c)  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).

> **Question three and its subparts were for the purpose of stimulating
> discussion by the members of the panel. The complete details of the
> responses to question three and its subparts are recorded on the
> meeting transcripts to which those interested are referred.**