Adults

The efficacy of budesonide delayed-release 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 of 8 weeks duration. 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. 1The 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 delayed-release 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 delayed-release capsules 9 mg daily in the morning to a comparator. At baseline, the median CDAI was 272. Budesonide delayed-release capsules 9 mg daily resulted in a significantly higher clinical improvement rate at Week 8 than the comparator. See Table 5.

Table 5: Clinical Improvement Rates (CDAI less than or equal to 150) After 8 weeks of Treatment

1.p=0.0004 compared to comparator. 

2.p=0.001 compared to placebo. 

3.This drug is not approved for the treatment of Crohn’s disease in the United States. 

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 delayed-release 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 delayed-release 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 delayed-release capsules 9 mg once daily, budesonide delayed-release 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 delayed-release capsules dose levels were statistically different from placebo (Table 5). The recommended dosage of budesonide delayed-release 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 delayed-release 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 delayed-release capsules 9 mg once daily, budesonide delayed-release 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 delayed-release capsules 9 mg daily and the prednisolone groups in Study 4. In Study 5, 13% fewer patients in the budesonide delayed-release 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 64.58 ng/mL) was significantly higher in the budesonide delayed-release capsules groups in both trials (60% to 66%) than in the prednisolone groups (26% to 28%) at Week 8.

Pediatrics (8 to 17 Years of Age)

The effectiveness of budesonide delayed-release capsules, in pediatric patients aged 8 to 17 years, who weigh more than 25 kg with mild to moderate active Crohn’s disease (defined as Crohn's Disease Activity Index (CDAI) ≥ 200) involving the ileum and/or the ascending colon, was assessed in one randomized, double-blind, active control study. This study compared budesonide delayed-release capsules 9 mg once daily, with prednisolone, administered at tapering doses starting from 1 mg/kg. Twenty-two (22) patients were treated with budesonide delayed-release capsules capsules and 24 patients were treated with prednisolone. After 8 weeks of treatment, 55% (95% CI: 32%, 77%) of patients treated with budesonide delayed-release capsules reached the endpoint (CDAI ≤150), as compared to 68% (95% CI: 47%, 89%) of patients treated with prednisolone. The average number of liquid or very soft stools per day (assessed over 7 days) decreased from 1.49 at baseline to 0.96 after treatment with budesonide delayed-release capsules and 2.00 at baseline to 0.52 after treatment with prednisolone. The average daily abdominal pain rating (where 0=none, 1=mild, 2=moderate, and 3=severe) decreased from 1.49 at baseline to 0.54 after treatment with budesonide delayed-release capsules and 1.64 at baseline to 0.38 after 8 weeks of treatment with prednisolone.

Use of budesonide delayed-release capsules in this age group is supported by evidence from adequate and well-controlled studies of budesonide delayed-release capsules in adults, and by safety and pharmacokinetic studies performed in pediatric patients.