Long-term safety and effectiveness of lubiprostone, a chloride channel (ClC-2) activator, in patients with chronic idiopathic constipation

Abstract

Background: Lubiprostone helps relieve constipation in short-term 4-week studies. There are limited data on long-term pharmacological treatment with lubiprostone for chronic idiopathic constipation.

Aims: To examine the long-term safety and effectiveness of lubiprostone in patients with chronic idiopathic constipation.

Methods: In this prospective, multicenter, open-labeled trial, 248 patients aged ≥18 years with chronic idiopathic constipation were directed to take lubiprostone 24 mcg BID as needed for 48 weeks. Patients were allowed to decrease the dose in response to the perceived severity of constipation and need for relief. Hematology and chemistry profiles and assessment of constipation symptoms and its severity were performed at all visits. Adverse events (AEs) were recorded.

Results: Of the 248 patients who entered the trial, 127 (51%) completed the trial. A dose reduction was observed in 17% of the patients, resulting in an average study medication exposure across the study of approximately 1.7 capsules (or approximately 40.8 mcg) per day. The most common treatment-related AEs were nausea (19.8%), diarrhea (9.7%), abdominal distension (6.9%), headache (6.9%), and abdominal pain (5.2%). No deaths were reported and of the 16 reported serious AEs, one was considered possibly treatment related. Average changes in serum electrolytes were not clinically relevant at any time point during the study. On average, lubiprostone significantly (p < 0.0001) reduced patient-reported constipation severity, abdominal bloating, and abdominal discomfort across 48 weeks when compared to baseline.

Conclusions: During this 48-week open-label study, lubiprostone was well tolerated. Bowel symptoms consistently improved over 48 weeks in adult patients with chronic idiopathic constipation.

Fig. 1

Flow of participants through each stage of the study. Single asterisk One patient hospitalized before receiving study medication; one patient lost to follow-up. Double asterisk Two patients discontinued the trial before receiving study medication in the open-labeled phase

Fig. 2

Mean symptom ratings for constipation severity, abdominal bloating, and abdominal discomfort with lubiprostone 24 mcg BID. End of treatment is defined as the last non-missing, post-baseline treatment period value. Follow-up is 2 weeks after end of treatment