Baker, D.E. (2007). Lubiprostone: A new drug for the treatment of chronic idiopathic constipation. Reviews in Gastroenterological Disorders, 7, 214–222.

In phase III, placebo-controlled studies, lubiprostone 24 mcg twice daily was compared to placebo. Studies 1, 2, and 3 comprised a two-week drug-free period followed by treatment with lubiprostone 24 mcg twice daily for four weeks, followed by randomization to continue lubiprostone or placebo.

Open-label studies used lubiprostone 24 mcg twice daily. Three studies of long-term clinical safety assessed lubiprostone administered for 12 months in patients with chronic idiopathic constipation.

Phase III Studies

• Patients were included in the study if they had constipation, defined as fewer than three spontaneous bowel movements per week plus a six-month history of at least one other Rome II criteria for functional constipation.
• Study 1 reported on a sample of 242 patients. Mean patient age was 48.6 years. The sample was 90% female and 86% Caucasian.
• Study 2 reported on sample of 237 patients who were predominantly female and Caucasian.
• Study 3 reported on a sample of 128 patients with chronic constipation.

Open-Label Studies

• Three studies reported on a sample of 871 patients with chronic idiopathic constipation.
• Mean patient age was 51 years. Nineteen percent of the sample (n = 163) was aged 65 years or older.
• The sample was 86% female and 87% Caucasian.

• Phase III studies
  • Studies 1 and 2: double-blind, placebo-controlled
  • Study 3: placebo-controlled randomized controlled trial (RCT)
• Open-label studies

• In studies 1 and 2, the primary endpoint was frequency of spontaneous bowel movements (BMs) after initiation of double-blind treatment.
• In study 3, a responder was defined as having three or more spontaneous BMs per week during lubiprostone therapy and was converted to nonresponder status (fewer than three spontaneous BMs per week) during the randomized phase for the placebo group.

Study 1 and 2

• Spontaneous BMs increased during all four weeks of lubiprostone treatment in both studies. In study 1, frequencies ranged from 5.1 to 5.7 in the lubiprostone group and 2.8 to 3.5 in the placebo group (p < 0.002 at all weeks). Results were similar for study 2.
• Time to spontaneous BM was shorter in the lubiprostone group. In study 1, spontaneous BM occurred in 56.7% of patients in the lubiprostone group within 24 hours of the first dose compared to 36.9% in the placebo group (p= 0.0024). In study 2, spontaneous BMs occurred in 69.9% of patients in the lubiprostone group within 24 hours of the first dose compared to 31.9% in the placebo group (p < 0.0001).

Study 3

• Spontaneous BMs increased from 1.36 per week at baseline to 6.25, 5.94, 5.52, and 6.2 per week during weeks 1, 2, 3, and 4, respectively (p < 0.0001 at all weeks).
• During the randomization phase, spontaneous BMs progressively declined for the placebo group. At week 7, frequency of spontaneous BMs was 5.59 for the lubiprostone group (p = 0.0223 ) versus 3.04 in the placebo group (p = 0.0223) compared to baseline.

Open-Label Studies

• Lubiprostone reduced abdominal bloating, abdominal discomfort, and severity of constipation over six to 12 months of treatment, and significant improvements were reported for constipation severity, bloating, and abdominal discomfort scores (p < 0.001).
• Although the incidence of adverse events was low overall, incidence of nausea was higher. Older adults had fewer adverse events.

Placebo-controlled RCTs demonstrated lubiprostone was well tolerated and not associated with severe adverse effects. However, incidence of nausea was higher. Comparative studies with other therapies are needed.

• The duration of constipation was not described.
• Information related to history of previous types of therapies used to treat constipation was lacking.
• The studies lacked a control group.
• Data were from publications of abstracts only. No peer journal articles were reviewed.
• No studies included patients with cancer.