A Randomised, Double-blind, Placebo-controlled, Five* Parallel Groups, Dose Finding Study of BIRB 796 BS (10, 20, 30, and 60 mg*) Administered Twice a Day Orally Over 8 Weeks in Patients With Moderate to Severe Crohn's Disease Followed by a 18 Weeks Treatment Extension in Patients With Clinical Remission or Clinical Response After 8 Weeks Treatment With the Respective Dose of BIRB 796 BS - Extension Phase. * Subsequent to Amendment 4 (Dated 11 Jun 2002) a 60 mg b.i.d. Group Was Included.
A Randomised, Double-blind, Placebo-controlled, Five* Parallel Groups, Dose Finding Study of BIRB 796 BS (10, 20, 30, and 60 mg*) Administered Twice a Day Orally Over 8 Weeks in Patients With Moderate to Severe Crohn's Disease Followed by a 18 Weeks Treatment Extension in Patients With Clinical Remission or Clinical Response After 8 Weeks Treatment With the Respective Dose of BIRB 796 BS - Extension Phase. * Subsequent to Amendment 4 (Dated 11 Jun 2002) a 60 mg b.i.d. Group Was Included.
The primary objective of this extension study was to obtain long-term safety data for BIRB 796 BS in patients with moderate to severe Crohn's disease after 26 weeks of treatment. Secondary objectives were the evaluation of efficacy of BIRB 796 BS to induce clinical remission and response over 26 weeks of treatment.
Inclusion Criteria:
Male or female patient of 18 to 65 years of age
Provision of written informed consent in accordance with Good Clinical Practice and local legislation prior to any study procedures
Diagnosis of Crohn's disease documented for at least 6 months. Preferably, inflammatory activity of the bowel should be confirmed by endoscopy within the last 3 months
Moderate to severe Crohn's disease, CDAI ≥220 to ≤450, at baseline (visit 2)
Any of the following therapy, provided the respective criteria for dosage, duration and stability were satisfied:
The following patients were included in the 18-week treatment extension:
Patients who received BIRB 796 BS for 8 weeks and reached:
Patients who were willing to continue with their treatment
Exclusion Criteria:
Pregnancy (to be excluded at visit 2 by urine β-human chorion-gonadotropin-test in women of childbearing potential) or breast feeding
Female patients of childbearing potential (not 6 months post-menopausal or surgically sterilised) not using an approved form of birth control (hormonal contraceptives orally or in depot, intrauterine device)
Patients without signs of inflammation of the bowel in the initial colonoscopy of the substudy
Patients with colostomy or ileostomy
Planned or needed surgery during the conduct of the trial due to Crohn's disease or for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage
Known or suggested severe fixed symptomatic stenosis of the small or large intestine
Severe underlying disease in particular of the GI tract (e.g. irritable bowel syndrome, celiac disease, infectious colitis)
Patients with pathogens or Clostridium difficile toxin detected in the stool culture in the screening period
Other infectious, ischemic, or immunological diseases with gastrointestinal involvement
Patients with short bowel syndrome
Patients who had had a treatment failure with a tumor necrosis factor (TNF)-blocking agent. Treatment failure was defined as not achieving a clinical response (improvement of ≥70 points in CDAI within 4 weeks) in a clinical trial or - in clinical practice -discontinuation of the TNF-blocking agent due to ineffectiveness (changed according to amendment 1, dated 16 January 2002)
Treatment with cyclosporine A within 12 weeks prior to visit 2
Last dose given within the specified time period before visit 2 for the following compounds:
Treatment with anti-inflammatory medication deviating from the criteria for dosage, and stability as provided in the inclusion criteria
Patients treated with any of the following therapy:
Treatment with:
Active infection or serious infectious diseases resulting in hospitalisation or requiring systemic anti-infective therapy within 4 weeks before visit 2
Serologic evidence of active hepatitis B and/or C
Known HIV-infection
History of prior tuberculosis infection or suspicion of active infection at screening based on chest X-ray done within 6 months prior to treatment phase
History of cardiovascular, renal, neurologic, psychiatric, liver, immunologic, or endocrine dysfunction if they were clinically significant. A clinically significant disease was defined as one which, in the opinion of the investigator, may have either put the patient at risk because of participation in the study or as a disease which may have influenced the results of the study or the patient's ability to participate in the study
Recent history of heart failure (one year or less) or myocardial infarction or patients with any cardiac arrhythmia requiring drug therapy (changed by amendment 1, dated 16 January 2002)
ECG results outside of the reference range of clinical relevance including, but not limited to QTcB >480 msec, PR interval >240 msec, QRS interval >110 msec
History of malignant disease in the last 5 years or suspicion of active malignant disease except successfully treated squamous or basal cell carcinoma of the skin and except patients with cervical carcinoma in situ who have had adequate treatment and follow up
Clinically significant abnormal baseline haematology, blood chemistry or urinalysis if the abnormality defines a disease listed as an exclusion criterion
Any of the following specific laboratory abnormalities at visit 1:
History of drug or alcohol abuse within the past two years or active drug or alcohol abuse
Participation in another clinical trial within 4 weeks or 5 half-lives of the respective investigational agent, whichever was longer
Hypersensitivity to trial drug
Inability to comply with the protocol