Summary of Clinical Study Results (Version 1.0)

Transcription

1 Pantoprazole BY1023/M /2006 (1.0) 1 of 6 Summary of Clinical Study Results (Version 1.0) Study Protocol BY1023/M3-319 Clinical Study Report 139/2006 Title of the study: Safety and efficacy of pantoprazole 20 mg vs. esomeprazole 20 mg with attention on thyroid parameters over 2 years in patients with symptomatically healed reflux esophagitis, preceded by a 4 week acute phase with 40 mg of the respective PPI EudraCT Number: Not applicable. Clinicaltrials.gov Identifier: Not applicable. Version Date:

2 Pantoprazole BY1023/M /2006 (1.0) 2 of 6 Title of the study: Safety and efficacy of pantoprazole 20 mg vs. esomeprazole 20 mg with attention on thyroid parameters over 2 years in patients with symptomatically healed reflux esophagitis, preceded by a 4 week acute phase with 40 mg of the respective PPI Investigators: The study was a multicenter study and conducted by gastroenterologists from Brazil (3), Germany (20), Hungary (9), and Italy (6). Coordinating investigator: 2, Konstanz, Germany M.D., ALTANA Pharma AG, Byk-Gulden-Strasse Study center(s): 38 centers enrolled patients in Brazil, Germany, Hungary, and Italy. Publication (reference): Not applicable Studied period (years): November 2002 September 2005 Clinical phase: III Objectives: To compare the safety and efficacy of pantoprazole 20 mg versus esomeprazole 20 mg in patients symptomatically healed from GERD stage II/III (Savary-Miller) in a two years maintenance phase with respect to thyroid parameters. Methodology: Randomized, double-blind, multicenter, multinational, parallel group comparison No. of subjects (total and for each treatment): Total number of safety set - acute phase: 391 Safety set acute phase pantoprazole 40 mg: 193 Safety set acute phase esomeprazole 40 mg: 198 Total number of safety set maintenance phase: 328 Safety set maintenance phase pantoprazole 20 mg: 161 Safety set maintenance phase esomeprazole 20 mg: 167 Total number of per protocol set acute phase: 290 Per protocol set acute phase pantoprazole 40 mg: 144 Per protocol set acute phase esomeprazole 40 mg: 146

3 Pantoprazole BY1023/M /2006 (1.0) 3 of 6 Total number of per protocol set maintenance phase: 252 Full analysis set maintenance phase - pantoprazole 20 mg: 127 Full analysis set maintenance phase - esomeprazole 20 mg: 125 Diagnosis and criteria for inclusion: Male or female outpatients of at least 18 years of age with endoscopically GERD stage II/III (Savary-Miller stage) Test product acute phase: Pantoprazole Dose: 40 mg Duration of treatment: 4 weeks acute healing phase Test product maintenance phase: Pantoprazole Dose: 20 mg Duration of treatment: 24 months maintenance phase Reference product acute phase: Esomeprazole Dose: 40 mg Reference product maintenance phase: Esomeprazole Dose: 20 mg

4 Pantoprazole BY1023/M /2006 (1.0) 4 of 6 Relapse medication maintenance phase: Pantoprazole or esomeprazole Dose: 20 mg Criteria for evaluation: Primary variable: Parameters triiodothyronine (T3), thyroxine (T4), thyroid binding globulin (TBG), and the thyroid stimulating hormone (TSH) in patients enrolled into the maintenance phase Secondary variables: Thyroid parameters free T3 (ft3) and free T4 (ft4) Clinically relevant deviations of the thyroid laboratory parameter Freedom from leading GERD symptoms for at least 3 days prior to the control visit (after 4 weeks) depending of H. pylori status at study entry Symptomatic Relapse Statistical methods: For the primary variables T3, T4, TBG, and TSH and the secondary variables ft3 and ft4, the comparison between the two treatments was based on the differences between the value at visit V9 and the value at the baseline visit V0.Differences between the treatments were estimated by the Hodges-Lehmann estimator and its two-sided 95% confidence interval according to Moses. The recorded adverse events were coded according to MedDRA. The adverse events were summarized by treatment, system organ class, preferred-term, and intensity. The rate of patients with at least one adverse event and the corresponding asymptotic two-sided 95% confidence interval were given for each treatment.

5 Pantoprazole BY1023/M /2006 (1.0) 5 of 6 SUMMARY - CONCLUSIONS Summary: Efficacy The GERD related symptoms were assessed at each visit by the investigator on a 4-point Likert scale. During the acute phase 97.92% of the patients treated with pantoprazole and 97.26% of the patients treated with esomeprazole were relieved from the leading GERD symptoms heartburn, acid regurgitation, and dysphagia. Symptomatic relapse was calculated as when at least one of the leading GERD symptoms was present for at least 3 days prior to the respective visit. Overall, in both treatment groups more than 94% of the patients remained in symptomatic remission during the maintenance phase. Safety Equivalence of pantoprazole and esomeprazole regarding the changes in the thyroid parameters T3, T4, TBG, TSH, ft3, and ft4 was concluded, because the calculated 95% confidence intervals of the respective Hodges-Lehmann estimation were always completely within the predefined margins. Between the baseline value at V0 and the end of the study similar changes in the thyroid parameters were observed for all thyroid parameters in both treatment groups. Specifically, T3 and T4 decreased while TBG and TSH increased slightly. The biologically active free fractions of the thyroid hormones showed divergent changes, i.e., ft3 increased while ft4 decreased in both treatment groups. These changes were regarded to be without clinical relevance, as there was no relation between the direction and magnitude of the pre-post TSHchange and the respective change in e.g. T4 on an individual patient level. In total, 65.2% of all patients of the safety set experienced a treatment emergent adverse event (255 patients out of 391 patients), of which 124 patients (64.2%) were treated with pantoprazole and 131 patients (66.2%) were treated with esomeprazole. No patient died during the course of this study. All treatment-emergent serious adverse events were assessed as unrelated or unlikely to study medication intake. The adverse events reported during the

6 Pantoprazole BY1023/M /2006 (1.0) 6 of 6 course of this study revealed that the safety profile of pantoprazole 20 mg was comparable to that of esomeprazole 20 mg during long term treatment. Conclusions: Equivalence of pantoprazole 20 mg and esomeprazole 20 mg regarding changes in thyroid parameters in long-term treatment was shown. In addition, both substances were equally efficacious in the treatment of GERD stages II/III, and GERD was controlled in 94% of patients with either pantoprazole or esomeprazole during two years of maintenance treatment. Both drugs were well tolerated and safe.