Released by FDA: 10/2/01.  Posted by FDA:  10/9/01

Christine Duffy Smith
Promotional Regulatory Affairs, Director 
AstraZeneca LP
725 Chesterbrook Blvd. 
Wayne, PA 29087-5677

RE:     NDA 20-768
          Zomig© (zolmitriptan) Tablets, 2.5 mg and 5 mg 
          MACMIS #9983

Dear Ms. Smith:

This letter is to notify you that the Division of Drug Marketing, Advertising, and Coimrnunications (DDMAC) has identified a promotional detail aid (#201906) for Zomig® (zohnitriptan) Tablets that is misleading and in violation of the Federal Food, Drug, and Cosmetic Act and applicable regulations.

The study was completed in 2 parts, Part 1 and Part 2. Part 1 was blinded, randomized and placebo controlled study of "persistent" migraine patients.  "Persistent" migraine headache was defined in the study as migraine headache with residual pain of any intensity two hours after initial treatment. P atients were initially treated with 2.5 mg of zolmitriptan and then received randomized treatment with 2.5 mg or 5 rng zolmitriptan, or placebo.  The primary endpoint was the proportion of patients with a reduction in headache severity two hours after taking the second randomized dose.  No significant difference between treatment groups was observed.  Any claims of clinical benefit based on this study would be unsubstantiated since the study produced no evidence that zolmitriptan was effective in the study population.

Part 2 of the study was a non-comparative, open-label continuation of Part ;1, in which patients treated multiple migraine headaches of any intensity with zohmitriptan.  Patients were required to take one 2.5 mg zolmitriptan tablet as initial therapy for their first two migraine headaches.  Thereafter, patients could choose to treat each subsequent initial, persistent or recurrent headache with either 2.5 mg or 5 ing zolmitriptan.  Results of Part 2 of the study provided descriptive data of patients' self-medication behavior. Among the secondary objectives of Part 2, patients were asked their "global impression" of treatment and control of their migraine upon completion or withdrawal from the study. 67.1% (1626/2425) of patients rated zolmitriptan as being better than any previous migraine therapy, and 19.4% (470/2425) as similar to their previous therapy.  Of patients with previous sumatrptan experience, 63.7% (1059/1663) rated zolmitriptan better than their previous therapy, and 21.5% (357/1663) rated zolmitriptan to be similar.  Part 2 of this study does not represent substantial evidence of superiority because it is not adequate and well-controlled and because it does not directly compare zolmitriptan with sumatriptan in a head-to-head fashion.

We therefore object to the use of the claims above in promotional materials for zohmtriptan because they are not supported by substantial evidence.  To address this objection, we recommend that you do the following:

l.  Immediately discontinue the use of this detail aid and any other promotional material with the same or similar messages.

2.  Respond to this letter within ten days.  Your response should include a statement of your intent to comply with the above, a list of promotional materials with the same or similar issues, and your methods for discontinuing these promotional materials.

If you have any questions or continents, please contact me by facsimile at (301) 594-6759, or at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD42, Room 17B-23, 5600 Fishers Lane Rockville, MD 20857.  We remind you that only written communications are considered official.  In all future correspondence regarding this particular matter, please refer to MACMIS ID #9983 in addition to the NDA number.

Sincerely,

 

Elaine J. Hu, R.Ph. 
Regulatory Review Officer 
Evidence Review Branch 
Division of Drug Marketing, 
       Advertising, and Communications