Questions for the Gastrointestinal Drugs
Advisory Committee
NDA: 21-200/S-005
Drug: Zelnorm® (tegaserod maleate) Tablets
Applicant: Novartis
Pharmaceuticals Corporation
Indication: treatment of chronic constipation
1. Efficacy
a. Discuss the
appropriateness of a primary efficacy endpoint of an increase of ≥1
complete spontaneous bowel movement per week vs. a total of ≥3 complete
spontaneous bowel movements per week.
b. Only 9 to 16% of
subjects were ≥65 years of age and the treatment effect was significantly
smaller in older patients. Are these
data adequate for an indication that is common in the elderly?
c. Only 9 to 14% of the
subjects were male and the treatment effect was smaller in males than
females. Are these data adequate to
support approval of Zelnorm® for use in
the treatment of chronic constipation in males?
d. Is the population
studied representative of patients with chronic constipation? If not, how do the populations differ?
e. Are the clinical trial
data adequate with respect to the population with chronic constipation that is
likely to be treated with Zelnorm®?
f.
Is
Zelnorm® effective for the treatment of
chronic constipation?
2. Safety
a. Post-marketing cases of
ischemic colitis and serious complications of diarrhea were not limited to
patients with irritable bowel syndrome.
What are the implications of these adverse events for patients with
chronic constipation?
b. The incidence of
diarrhea and discontinuations due to diarrhea was higher in patients
≥65 years of age. Is there
sufficient information that Zelnorm® is
safe for use in this age group?
c. Do the adverse event
data from the clinical trials and post-marketing surveillance provide adequate
evidence of safety of Zelnorm® for the
treatment of chronic constipation?
d. Should the information
on the post-marketing cases of ischemic colitis and intestinal ischemia be
moved from the PRECAUTIONS section to the WARNINGS section of the package
insert?
3. Should Zelnorm be approved for the proposed indication of the treatment of patients with chronic
constipation and relief of the associated symptoms of straining, hard or lumpy
stools, and infrequent defecation?