Table 1.

Phase II clinical trials of linaclotide in constipation-predominant irritable bowel syndrome.

Study/phase/design	Number of patients/sex/duration/doses studied	Primary endpoints	Efficacy results	Secondary endpoints	Efficacy results
Andresen et al. [2007]	N = 36	Gastric transit	No treatment effect	NA	NA
Phase IIa	Female patients = 100%	Small bowel transit	Increased ascending colon emptying t½ times (p = 0.015) and increased total colonic transit times at 48 h (p = 0.02) (for 1000 µg dose; p = 0.004)
Randomized, double-blind, placebo-controlled trial	5-day baseline and 5-day treatment periods	Colonic transit (by scintigraphy)	Increased stool frequency, decreased stool consistency, improved ease of passage, and time to first bowel movement (p < 0.001)
	Placebo, 100 and 1000 µg linaclotide	Bowel function (using stool diaries)
Johnston et al. [2010]	N = 420	Change in the number of CSBMs	For the 75, 150, 300, 600 µg linaclotide doses: mean change in CSBMs/week were 2.90, 2.49, 3.61 and 2.68 respectively (p < 0.01)	Effect on individual symptoms	Improved frequency of SBMs (p ≤ 0.001), CSBMs (p ≤ 0.01), severity of straining (p ≤ 0.001), stool consistency (p ≤ 0.001), and abdominal pain scores (p ≤ 0.05)
Phase IIb	Female patients = 92%		Proportion of patients who were CSBM responders was 25%, 19.5%, 32% and 24% respectively (all significant except for the 150 µg dose)	Proportion of CSBM responders Proportion of Global relief responders	Higher proportion of adequate relief responders
Randomized, double-blind, parallel-group, multicenter, placebo-controlled trial	12-week treatment period			Quality of life	Higher proportion of global relief responders
	Placebo, 75, 150, 300 and 600 µg linaclotide				IBS-QOL scores increased ≥14 points in all linaclotide treatment groups

CSBM, complete spontaneous bowel movement; IBS, irritable bowel syndrome; NA, not applicable; QOL, quality of life; SBM, spontaneous bowel movement.