Dexlansoprazole MR for Treatment for Nocturnal Heartburn in Patients with Symptomatic Nonerosive GERD

Abstract

Purpose: Nocturnal heartburn (HB) and sleep disturbances commonly occur in patients with GERD. These symptoms are important to treat since nighttime reflux creates a high risk for esophagitis and impacts quality of life. This study evaluated the effects of dexlansoprazole MR (DEX), a PPI with a Dual Delayed ReleaseTM formulation designed to extend the duration of acid suppression, in patients with nighttime symptoms. Methods: A multicenter, randomized, double-blind, placebo controlled, parallel group trial in patients aged 18-66 with symptomatic GERD, with no esophageal erosions based on endoscopy. The patients enrolled in the study had moderate to very severe nocturnal HB and GERD-related sleep disturbances on at least 3 of 7 nights based on twice daily diary entries, recorded upon waking and before bedtime. Night time was defined as the time at which the patient laid down to fall asleep to the time when the patient woke up and began daily activities. Patients received DEX 30 mg or placebo (PBO) orally, every morning for 4 weeks. In addition to the diary, patients completed questionnaires on sleep quality and work productivity at baseline and week 4. The primary endpoint was the % of nights without heartburn over 4 weeks. Secondary endpoints were % of patients with relief of nocturnal HB and % of patients with relief of GERD-associated sleep disturbances over the last 7 days of treatment. Relief was rigorously defined as 6 of 7 days without nighttime HB and at most 1 night with mild HB and 6 of 7 days without GERD associated sleep disturbances. Results: 305 patients were randomized. Patients taking DEX had a statistically significantly greater % of nights without HB during 4 weeks of treatment vs. PBO (median of 73% vs. 36%, respectively; Wilcoxon rank-sum test p<0.001); the therapeutic gain was greater in patients with more severe baseline symptoms. During the last 7 days of treatment, relief of nocturnal HB and relief of GERD-related sleep disturbances occurred in a significantly higher % of patients who received DEX vs. PBO (48% vs. 20%, and 70% vs. 48%, respectively; Fisher's exact test p<0.001 for both). Patients receiving DEX had significantly greater improvement in measurements of sleep quality and work productivity. There were no clinically significant differences between treatment groups regarding adverse events or other safety parameters. Conclusion: In patients with significant complaints of nighttime HB and associated sleep disturbances, DEX 30mg was highly effective in improving strictly defined symptoms of nighttime HB and sleep quality as well as work productivity. Sponsored by Takeda Global Research & Development Center, Inc., Deerfield, IL, USA. Disclosure: Ronnie Fass - Consultant - Takeda, Xenoport, Vecta, Eisai, Salix; Research Suuport - Takeda, Wyeth, AstraZeneca, Sucampo; Speakers Bureau - Eisai, Takeda. David Johnson-Consultant - Takeda, AstraZeneca, Esai, Novartis; Research Support - Takeda, AstraZeneca; Clinical Investigator; Takeda, AstraZeneca, Novartis. William Orr-Speaker, Consultant, Research Support - Takeda. M Claudia Perez, Cong Han, Reema Mody, Kathleen Stern-Employee: Takeda.