A dose-finding, double-blinded, parallel-group, placebo-controlled, Phase 2 study was conducted in patients with chronic idiopathic constipation. Following a 2-week baseline/washout period, patients (n = 127) were randomized to receive placebo (n = 33), AMITIZA 24 mcg/day (24 mcg once daily; n = 29), AMITIZA 48 mcg/day (24 mcg twice daily; n = 32), or AMITIZA 72 mcg/day (24 mcg three times daily; n = 33) for 3 weeks. Patients were chosen for participation based on their need for relief of constipation, which was defined as less than 3 spontaneous bowel movements (SBMs) per week. The primary efficacy variable was the daily average number of SBMs.

The study demonstrated that all patients who took AMITIZA experienced a noticeable improvement in clinical response. Based on the efficacy analysis, there was no statistically significant improvement in the clinical response beyond a total daily dose of 24 mcg during treatment weeks 2 and 3 (Figure 1).

Figure 1: Weekly Mean (± Standard Error) Spontaneous Bowel Movements (Dose-finding Study)

Efficacy Studies

Two double-blinded, placebo-controlled studies of identical design were conducted in patients with chronic idiopathic constipation. Chronic idiopathic constipation was defined as, on average, less than 3 SBMs per week along with one or more of the following symptoms of constipation for at least 6 months prior to randomization: 1) very hard stools for at least a quarter of all bowel movements; 2) sensation of incomplete evacuation following at least a quarter of all bowel movements; and 3) straining with defecation at least a quarter of the time.

Following a 2-week baseline/washout period, a total of 479 patients (mean age 47.2 [range 20– 81] years; 88.9% female; 80.8% Caucasian, 9.6% African American, 7.3% Hispanic; 1.5% Asian; 10.9% ≥ 65 years of age) were randomized and received AMITIZA 24 mcg twice daily (48 mcg/day) or placebo twice daily for 4 weeks. The primary endpoint of the studies was SBM frequency. The studies demonstrated that patients treated with AMITIZA had a higher frequency of SBMs during Week 1 than the placebo patients. In both studies, results similar to those in Week 1 were also observed in Weeks 2, 3, and 4 of therapy (Table 2).

Table 2: Spontaneous Bowel Movement Frequency Rates¹ (Efficacy Studies)

Bookmark this page: