Food and Drug Administration
Center for
Drug Evaluation and Research
Claudia H. Kawas, M.D.
(Chair)
Jerry S. Wolinsky, M.D.
FDA
Participants
Robert
Temple, M.D.
Russell Katz, M.D.
John Feeney, III, M.D.
Norman Hershkowitz, M.D., Ph.D
Executive Secretary
Anuja M.
Patel, M.P.H.
Steven
Ebert, Pharm. D. (Consumer Representative)
Gerald van Belle, Ph.D.
Jorge C. Kattah, M.D.
Emanuel J. Mignot, M.D., Ph.D
Lois E. Krahn, M.D.
David
Neubauer, M.D.
Industry Representative (Non-Voting)
Daniel Azarnoff , M.D.
These
summary minutes for the
I certify that I attended the
_______//S//_____________________ ________//S//_________________
Anuja
M. Patel, M.P.H Claudia
Kawas, M.D.
Executive
Secretary Chair
At
Open Public Hearing Speaker:
· Richard Gelula, MSW
Executive Director, National
Sleep Foundation
· Christin Engelhardt
Executive Director, American
Sleep Apnea Organization
Issue:
Discussion on supplementary
new drug application (SNDA 20-717 /S-008) Provigil (modafinil) Tablets,
Cephalon, Inc., indicated for use to improve wakefulness in patients with
excessive sleepiness associated with disorders of sleep and wakefulness.
FDA
Presentation
· Opening Remarks Russell
Katz, M.D.
Overview of Issues Director,
Division of Neuropharmacologic Drug Products, FDA
Sponsor Presentation
· Introduction Lesley
Russell, MBChB, MRCP
Vice President, Clinical
Research,
Cephalon Incorporated
· Review of Excessive
Sleepiness Thomas Roth, Ph.D.
Division Head, Sleep Disorders and
· Overview of Efficacy Rod Hughes, Ph.
D
Senior Director, Clinical
Research,
Cephalon Incorporated
· Overview of Safety Gwendolyn
Niebler, D.O.
Senior Director, Clinical
Research,
Cephalon Incorporated
· Conclusion Lesley
Russell, MBChB, MRCP
Vice President, Clinical
Research,
Cephalon Incorporated
Questions for Advisory
Committee
1. Using the International
Classification of Sleep Disorders (ICSD), the sponsor has defined “Disorders of
Sleep and Wakefulness Associated with Excessive Sleepiness.” Does the Committee agree with this
designation?
Yes – 7 No- 0 Abstain- 1
One member of the Committee deferred to the sleep experts.
2. The sponsor believes that
the above group can be divided into three categories, based on the presumed
cause of the excessive sleepiness. The categories are: sleep-wake
dysregulation, sleep disruption, and circadian misalignment. Does the Committee
agree with this classification?
Yes – 7 No-
0 Abstain- 1
One member of the Committee deferred to the sleep experts.
3. Does the Committee agree
that the disorders studied by the sponsor, narcolepsy, obstructive sleep apnea
(OSAHS), and shift work sleep disorder (SWSD), are representative of the three
categories described above?
Yes - 3 No- 5
Although the some members of
the committee agree with the three categories on presumed cause of excessive
sleepiness is an acceptable division for some, the Committee felt that the
definition of “representative” in the question was unclear. The Committee was told that “representative”
in this case meant that if the drug works in one of the diseases in the
category, could we assume that it works in all of them. There are times when one can make this
assumption, such as when you know that the diseases share pathophysiology and
thus are likely to respond to the same treatments. In this case, those who voted “no” felt that
we could not make this assumption. Additionally, individual members felt that the information provided by
the Sponsor was not enough information in terms of efficacy or safety of
Provigil for other diseases within the three subcategories.
One member of the committee
voted yes, provided that “representative” was substituted with “convenience
samples”.
4. Does the Committee agree
that the sponsor has submitted substantial evidence of effectiveness for the
indication, “…for the treatment of excessive sleepiness associated with
disorders of sleep and wakefulness…"?
Yes - 4 No- 4
Members expressed their
reservations such as the global nature of the indication given by the
Sponsor. Some felt that it is difficult
to highlight these three disorders and say that it is representative of all the
disorders.
5. Has the sponsor demonstrated
that Provigil can be used safely for this broad indication?
Yes - 5 No- 2
One member of the committee
felt that the sponsor demonstrated Provigil can be used safely for the broad
indication for narcolepsy and shift work sleep disorders but not for sleep
apnea patients. The member suggested that additional information be collected
in regards to safety in sleep apnea patients.
If
the Committee does not vote “yes” on questions 1-5:
1. Has the Sponsor provided
substantial evidence of effectiveness to support the use of Provigil in the
treatment of excessive sleepiness in patients diagnosed with OSAHS?
Yes - 8 No- 0
The vote was unanimous;
however, some members expressed reservations provided that Provigil be used as
adjunctive therapy to C-PAP (Continuous Positive Airway Pressure).
2. Has the Sponsor provided
substantial evidence of effectiveness to support the use of Provigil in the
treatment of excessive sleepiness in patients diagnosed with SWSD?
Yes
- 6 No- 2
Members expressed their opinion that this drug is the treatment
of a symptom not on the elimination of a disease and given the fact the drug
has a similar effect on that symptom for the other diseases discussed. The
committee suggested that strong labeling measures be taken by the Food and Drug
Administration to include the sleep apnea and shift work sleep disorders
(SWSD).
Committee members that voted “no” were concerned that the
criterion is for two independent studies and the Committee was presented one.
Furthermore, the conceptual issues of exactly what constitutes the SWSD as
oppose to those individuals who are doing shift work and experiencing
sleepiness; and also the effectiveness is questionable patients who are still
in a range of profound sleepiness.
Following
completion of discussion of the questions, the committee adjourned at
approximately
Prepared by:
Anuja M. Patel, M.P.H.
Executive Secretary
Peripheral and Central
Nervous System Drugs Advisory Committee