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Long-Term Safety of TAK-390MR, a PPI with a Novel Dual Delayed Release Formulation, in GERD Patients

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Dabholkar, Aruna MD*; Yu, Peter PhD; Paris, Maria MD

American Journal of Gastroenterology: September 2008 - Volume 103 - Issue - p S5–S6
Supplement Abstracts Submitted for the 73rd Annual Scientific Meeting of the American College of Gastroenterology: ESOPHAGUS
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Research & Development, TAP Pharmaceutical Products Inc., Lake Forest, IL.

Purpose: TAK-390MR, a novel modified release formulation of TAK-390 (an enantiomer of lansoprazole), produces a 2-peaked plasma drug concentration-time profile designed to extend the duration of acid suppression. TAK-390MR releases drug over a longer period than conventional delayed release PPIs and thereby requires higher daily doses. The purpose of this study was to assess the long-term safety of TAK-390MR using interim data from an ongoing randomized, open-label, extension study in nonerosive GERD patients.

Methods: Patients received TAK-390MR 60 mg (N = 153) or 90 mg (N = 160) orally once daily (QD) for 12 months (mo). Between-group comparisons were made using Fisher's exact test for adverse events (AEs), and 1-way ANOVA for mean changes of vital signs and laboratory values from baseline to mo 1, 3, 6, 9 & 12. Gastric biopsies performed at mo 12/Final Visit were tabulated by treatment and between-group comparisons were made using Fisher's exact test.

Results: Of 313 patients receiving study drug, 71% and 66% on TAK-390MR 60 and 90 mg experienced ≥1 AE. The most frequently reported treatment-emergent AE (TEAE) was upper respiratory infection (14% for each group); only 1 was considered to be related to study drug. Other frequently reported TEAEs in the 60- and 90-mg groups, respectively, were GI & abdominal pain (7%/13%); diarrhea (12%/8%); nausea & vomiting (8%/11%); headaches (7%/9%); musculoskeletal & connective tissue signs & symptoms (7%/4%); flatulence, bloating & distention (4%/7%). No statistically significant differences between treatment groups or dose-related trends were observed. 197 patients (105 on 60 mg/92 on 90 mg) completed ≥48 wks treatment; 12% discontinued due to an AE (most were GI related). The most common AE leading to premature discontinuation was diarrhea (3%). 19 patients (6%) reported serious TEAEs; 2 were considered possibly related to treatment (chest pain; auditory hallucination). 3 patients died of unrelated causes (asthma, leukemia, sepsis). As expected with PPI therapy, increases in mean fasting serum gastrin were seen at mo 3, 6, 9, and 12 and were not dose related. No clinically meaningful treatment differences were seen in labs, vital signs or gastric biopsy results. No reports of clinically concerning changes of adenocarcinoma or ECL-cell hyperplasia were observed on gastric biopsies.

Conclusion: TAK-390MR 60 and 90 mg QD were well tolerated for up to 12 mo. The safety profile was similar to that seen in trials with lansoprazole.

© The American College of Gastroenterology 2008. All Rights Reserved.