Spontaneous Bowel Movement Frequency Is Improved Over 12 Weeks of Lubiprostone Therapy in Opioid-induced Constipation Patients Regardless of Gender, Age, or Race: Pooled Analysis of Three Well-controlled Studies

Abstract

Purpose: To evaluate impact of demographic characteristics (gender, age, and race) on overall spontaneous bowel movement (SBM) frequency rates with 12-week oral lubiprostone (24 mcg BID) therapy in non-cancer pain patients with opioid-induced constipation (OIC). Methods: Data were pooled from three multicenter, double-blind trials in which adult patients with OIC (i.e., <3 SBMs/wk) were randomized to receive lubiprostone 24 mcg (n=659) or placebo (n=641) BID for 12 weeks. Overall change from baseline (CFB) in SBM frequency across the entire treatment period was assessed for the pooled population, as well as for select demographic categories (i.e., by gender, age, and race) to determine whether these factors impacted treatment response. Results: The mean age of enrolled subjects was 50.5 years (range: 20-89 years); 62.5% of the patients were women and 82.1% were white. The mean overall CFB in SBM frequency was statistically significantly improved for all patients treated for up to 12 weeks with lubiprostone as compared with placebo (2.8 vs 2.2 SBMs/wk, respectively; p<0.001). Overall SBM frequency changes were also statistically significantly improved with lubiprostone treatment in subgroup analyses of men and women (p≤0.004 for both populations). Although statistical significance was not achieved in elderly patients (≥65 years), likely due to the small size of this population (n=110), the absolute treatment difference between the lubiprostone and placebo arms in elderly was identical to the reported difference for the non-elderly population (+0.6 SBM/wk treatment advantage for lubiprostone vs placebo in both age subsets; p<0.001 for nonelderly). For the same endpoint, a larger treatment difference was observed for non-white patients treated with lubiprostone vs placebo overall (3.2 vs 2.5 SBMs/wk; n=224) relative to white patients overall (2.7 vs 2.2 SBMs/wk), though statistical significance was only achieved for the white population (n=1027; p<0.001). Conclusion: Over a 12-week treatment period, changes from baseline in SBM frequency were consistently higher with lubiprostone therapy versus placebo treatment regardless of patient gender, age, or race. Statistical separation between the lubiprostone and placebo arms was achieved overall, and for populations of men, women, white patients, and patients aged <65 years. Non-white patients and those ≥65 years of age reported the same or better response to lubiprostone therapy than their white and nonelderly counterparts, though statistical significance was not achieved due to relatively small patient numbers in these groups. This research was funded by Sucampo Pharma Americas, LLC, Bethesda, MD, and Takeda Pharmaceuticals International, Inc., Deerfield, IL. Disclosure - Byron Cryer has consulting relationships with AstraZeneca, Inc., Horizon Therapeutics, PLx Pharma, Pfizer Inc., POZEN, Inc., Ritter Pharma, and Sucampo Pharmaceuticals, Inc. Shadreck Mareya is an employee of Sucampo Pharma Americas, LLC. Taryn Joswick is an employee of Sucampo Pharma Americas, LLC. Gayle Dolecek is an employee of Sucampo Pharma Americas, LLC. Yijun Sun is an employee of Sucampo Pharma Americas, LLC. Ryuji Ueno is a Director of Sucampo AG, is an employee of Sucampo Pharma Americas, LLC, and is a shareholder of Sucampo Pharmaceuticals, Inc. This research was supported by an industry grant from Sucampo Pharma Americas, LLC; Takeda Pharmaceuticals International, Inc.