Sponsor. Generic Drug Name. Trial Indication(s) Protocol Number. Protocol Title. Clinical Trial Phases. Study Start/End Dates

Transcription

1 Sponsor Novartis Generic Drug Name Lumiracoxib Trial Indication(s) Safety study effects on small bowel Protocol Number CCOX189A2425 Protocol Title A 16-day, randomized, double-blind, double-dummy, placebo-controlled, parallel-group trial comparing lumiracoxib 100 mg od with naproxen 500 mg bid plus omeprazole 20 mg od and placebo in healthy volunteers to confirm the safety and tolerability of lumiracoxib in the small bowel Clinical Trial Phases Phase IV Study Start/End Dates 11 May 2006 to 29 Sep 2006 Reason for Termination (If applicable) Not Applicable Page 1

2 Study Design/Methodology This was an international randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. Eligible patients who completed a screening and run-in period were randomized to receive 16 days of double-blind treatment with lumiracoxib 100 mg o.d., naproxen 500 mg b.i.d. + omeprazole 20 mg o.d. or placebo. The Placebo arm was used to assay sensitivity. Centers 2 centers in Germany and 1 center in UK. Objectives: Primary Objective: To demonstrate, by video capsule endoscopy (VCE), that the percentage of subjects with one or more small bowel mucosal breaks (with or without hemorrhage) was significantly lower for lumiracoxib than for naproxen + omeprazole. Test Product (s), Dose(s), and Mode(s) of Administration Lumriacoxib (100 mg) tablet was orally administered once daily, or naproxen 500 mg administered orally twice daily along with omeprazole 20 administered once daily or matching placebo administered orally Statistical Methods The primary variable - presence or absence of small bowel mucosal breaks (with or without hemorrhage) as detected by video capsule endoscopy (VCE) was tested using a Cochran-Mantel-Haenszel test stratified by country. All analyses were performed using all randomized subjects who completed 15 days of study medication and who had valid end-of-study VCEs. Number of events were analyzed using a Wilcoxon rank sum test stratified by country. Changes from baseline in value of lower GI permeability and in value of small bowel inflammation were analyzed using an ANCOVA (analysis of covariance) model adjusting for GI permeability at baseline and medication. Study Population: Key Inclusion/Exclusion Criteria Inclusion criteria Page 2

3 Provided written informed consent. Healthy male or female subject s 18 years of age. Exclusion criteria Pregnant, lactating or at risk of becoming pregnant during the study. Use of other investigational drugs, regular use and any use within two weeks before visit 1 of aspirin or other NSAIDs or other medications with suspected ulcerogenic potential, use of anti-ulcer medications, need for regular use of medication (other than oral contraceptives and hormone replacement therapy). Active gastrointestinal disease or history of abdominal surgery or radiation, any other symptoms of luminal narrowing or risk factors for delayed transit; known or suspected complete or partial stenosis of the small intestine or swallowing disorders; prior gastric or intestinal surgery or history of delayed gastric emptying or diabetic gastroparesis. Hemoglobin less than 10 g/dl (women) or 12 g/dl (men) at screening. Visit 2 positive fecal occult blood test results, visit 2 VCE showing any lesion. Current smokers and subjects who smoked within one month prior to visit 1. Participant Flow Table Subject disposition (randomized population) Page 3

4 Baseline Characteristics Demographic characteristics at baseline (safety population) Page 4

5 Summary of Efficacy Primary Outcome Result: Page 5

6 Number of subjects (%) with at least one small bowel mucosal break with or without hemorrhage, treatment comparisons, (safety completers with valid EOS VCE) 1 Odds ratio is first group/second 2 CMH test stratifying for country Summary of Safety Safety Results AEs overall and by primary system organ class (safety population) Primary system organ classes are presented in order of descending frequency of AE reports for the LUM 100 mg od study medication group AEs by system organ class and preferred term (safety population) Page 6

7 Preferred terms within each primary system organ class are presented in order of descending frequency of AE reports for the LUM 100 mg od study medication group Serious Adverse Events and Deaths Two subjects treated with placebo experienced non-fatal SAE s and no deaths were reported. Page 7

8 Other Relevant Findings Not Applicable Date of Clinical Trial Report 17 Jul 2007 Page 8