STUDY 303
A Phase III, Randomized, Multi-Center, Open-Label, 12 to 14 Month
Extension Study to Evaluate the Safety and Tolerability of Mesalamine
Given Once Daily Vs. Twice Daily for the Maintenance of Ulcerative
Colitis in Remission
Study 303: Objectives
 Study design
 Patient disposition
 Definitions
 Safety of 8-week acute extension
 Efficacy of 8-week acute extension
 Safety of 12-month long-term extension
 Efficacy of 12-month long-term extension
 Summary
Study Design of 303
 Open-label, multicenter, phase III study
 12–14-month extension of the Lichtenstein et al. and Kamm et al.
studies (parent studies)
 Two phases
 8-week acute extension phase
 Patients not in remission at the end of the parent studies
 Mesalamine 4.8 g/day (given b.i.d.)
 12-month long-term extension phase
 Patients in remission at the end of the parent studies or the end of
the 8-week acute extension phase
 Mesalamine 2.4 g/day (given q.d. or 1.2 g b.i.d.)
Adapted from Kamm et al. Gut 2008;57(7):893-902.
Study 303 End Points1
 Primary objective: to assess the long term safety and tolerability of
Mesalamine 2.4 g/day over 12 months
 Efficacy was not a primary endpoint of Study 303
 Secondary objectives included:
 Safety in acute extension phase
 Time to relapse in long-term extension phase
 Patients in remission at 12 months
 Patient satisfaction
Adapted from Kamm et al. Poster presented at BSG 2007 1.
Modified* Ulcerative Colitis-Disease Activity Index
Mild
(Score = 1)
Moderate
(Score = 2)
Severe
(Score = 3)
Rectal bleeding
Streaks of blood
Obvious blood
Mostly blood
Stool frequency
1-2/day > normal
3-4/day > normal
> 4/day > normal
Mucosal appearance
Erythema
Marked erythema
Ulceration
Decreased vascular pattern
Friability
Spontaneous bleeding
Minimal granularity
Granularity
Friability
Absent vascular pattern
*
*
Bleeding minimal trauma
No ulcerations
PGA
(Physician’s Global
Assessment)
Mild
Moderate
* Friability moved from Score of 1 to 2
Adapted from Kamm et al. Gastroenterology 2007;132:66–75.
Severe
End Point Definitions
 Relapse: Withdrawal from the study due to a requirement for
alternative treatment (including a dose increase or surgery) for an
exacerbation of UC
 Remission: Modified UC-DAI score 1, calculated as a score of 0
for rectal bleeding and for stool frequency, a combined
Physician’s Global Assessment (PGA) and sigmoidoscopy score
of 1, no mucosal friability, and a sigmoidoscopy score reduction
of 1 point or more from baseline
Adapted from Kamm et al. 2008;57(7):893-902.
Patient Disposition1,2
623
(Parent Studies)
558 (89.6%)
(Rolled over into 303)
312 (56%)
(Acute Extension Phase)
213
246 (44%)
(Long-term Extension
Phase)
(68%)
459 (Safety population)
(Long-term Extension
Phase)
225
(q.d. Group)
Adapted from:
1Kamm et al. Poster presented at BSG 2007.
2 Kamm et al. Gut 2008;57(7):893-902.
234
(b.i.d. Group)
Efficacy Results:
8-Week Acute Extension Phase
8-Week Acute Extension Phase: Efficacy Results
 Remission
 59.5% of patients in the efficacy population (n=304) achieved remission
 Modified UC-DAI score
 Mean reduction of 3.9 ± 2.8 points from week 0* to end point
 Mean reduction of 5.0 ± 2.7 from parent study baseline to end point
 Symptom improvement
 65.1% of patients had a score of 0 for stool frequency at end point
compared to 7.9% at week 0
 80.6% of patients had a score of 0 for rectal bleeding at end point
compared to 27.3% at week 0
*Week 0=First study visit of the acute extension phase
Adapted from Lichtenstein GR, et al. Poster presented at ACG, 2007.
Patients in Remission After Eight Weeks’
Extension Therapy
Up to 8 weeks’
active treatment
(n = 107)
Up to 16 weeks’
active treatment
(n = 78)
(n = 78)
Prior treatment
(n = 41)
Number of patients (%)
8-Week Acute Extension Phase:
Sigmoidoscopy Scores
*Week 0=First study visit of the acute extension phase
Adapted from Lichtenstein et al. Poster presented at ACG 2007.
STUDY 303 Acute Extension Phase Conclusions1,2
 Mesalamine 4.8 g/day (2.4 g dosed b.i.d.) was welltolerated in the 8-week acute extension phase
 Safety profile similar to that of the parent studies
(Lichtenstein et al. and Kamm et al.)
 Mesalamine 4.8 g/day for up to 4 months was welltolerated
 Approximately 60% of patients achieved remission, using
stringent clinical and endoscopic criteria
Adapted from: 1Lichtenstein et al. Poster presented at APhA 2007.
2 Lichtenstein et al. Poster presented at ACG 2007.