Adults

The efficacy of BUDESONIDE Capsules, were evaluated in 994 patients with mild to moderate active Crohn’s disease of the ileum and/or ascending colon in 5 randomized and double- blind studies. The study patients ranged in age from 17 to 85 (mean 35), 40% were male and 97% were white. The Crohn’s Disease Activity Index (CDAI) was the main clinical assessment used for determining efficacy in these 5 studies. The CDAI is a validated index based on subjective aspects rated by the patient (frequency of liquid or very soft stools, abdominal pain rating and general well-being) and objective observations (number of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal mass, body weight and hematocrit). Clinical improvement, defined as a CDAI score of less than or equal to 150 assessed after 8 weeks of treatment, was the primary efficacy variable in these 5 comparative efficacy studies of BUDESONIDE Capsules. Safety assessments in these studies included monitoring of adverse reactions. A checklist of potential symptoms of hypercorticism was used.

One study (Study 1) compared the efficacy of BUDESONIDE Capsules, 9 mg daily in the morning to a comparator. At baseline, the median CDAI was 272. BUDESONIDE Capsules, 9 mg daily resulted in a significantly higher clinical improvement rate at Week 8 than the comparator. See Table 5.

Two placebo-controlled clinical trials (Studies 2 and 3) were conducted. Study 2 involved 258 patients and tested the effects of graded doses of BUDESONIDE Capsules (1.5 mg twice daily, 4.5 mg twice daily, or 7.5 mg twice daily) versus placebo. At baseline, the median CDAI was 290. The 1.5 mg twice daily arm (data not shown) could not be differentiated from placebo. The 4.5 mg twice daily arm was statistically different from placebo (Table 5), while no additional benefit was seen when the daily BUDESONIDE Capsules dose was increased to 15 mg per day (data not shown). Study 3 was a 3-armed parallel group study. The groups were treated with BUDESONIDE Capsules 9 mg once daily, BUDESONIDE Capsules 4.5 mg twice daily and placebo for 8 weeks, followed by a 2-week double-blind taper phase. The median CDAI at baseline was 263. Neither 9 mg daily nor 4.5 mg twice daily BUDESONIDE Capsules dose levels were statistically different from placebo (Table 5). The recommended dosage of BUDESONIDE Capsules for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon in adults is 9 mg once daily in the morning for up to 8 weeks [see Dosage and Administration (2.1)].

Two clinical trials (Studies 4 and 5) compared BUDESONIDE Capsules with oral prednisolone (initial dose 40 mg per day). Study 4 was a 3-armed parallel group study. The groups were treated with BUDESONIDE Capsules 9 mg once daily, BUDESONIDE Capsules 4.5 mg twice daily and prednisolone 40 mg (tapered dose) for 8 weeks, followed by a 4-week double blind taper phase. At baseline, the median CDAI was 277. Equal clinical improvement rates (60%) were seen in the BUDESONIDE Capsules 9 mg daily and the prednisolone groups in Study 4. In Study 5, 13% fewer patients in the BUDESONIDE Capsules group experienced clinical improvement than in the prednisolone group (no statistical difference) (Table 5).

The proportion of patients with normal plasma cortisol values (greater than 150 nmol/L) was significantly higher in the BUDESONIDE Capsules groups in both trials (60% to 66%) than in the prednisolone groups (26% to 28%) at Week 8.

Pediatric use information is approved for Perrigo Pharma International DAC’s ENTOCORT EC (budesonide) capsules. However, due to Perrigo Pharma International DAC’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.