Table 4 Table 4. Other study assessment results (intention to treat analysis set)Continued.

	Placebo b.i.d. (n=89)	Tenapanor b.i.d.
	5 mg (n=87)	20 mg (n=87)	5 mg (n=87)	20 mg (n=87)
Abdominal pain severity score a
Change from baseline at week 12 end point, LS mean	−37.0	−37.6	−38.9	−50.4
95% CI	(−45.1, −28.9)	(−45.6, −29.7)	(−47.0, −30.8)	(−58.8, −42.1)
Difference tenapanor vs. placebo, LS mean	–	−0.6	−1.9	−13.4
95% CI	–	(−11.2, 10.0)	(−12.5, 8.7)	(−24.1, −2.8)
P value	–	0.910	0.724	0.014
CSBMs/week
Change from baseline at week 12 end point, LS mean	0.9	1.7	2.2	2.7
95% CI	(0.2, 1.7)	(1.0, 2.4)	(1.4, 2.9)	(2.0, 3.5)
Difference tenapanor vs. placebo, LS mean	–	0.8	1.2	1.8
95% CI	–	(−0.2, 1.7)	(0.3, 2.2)	(0.8, 2.8)
P value	–	0.115	0.012	<0.001
SBMs/week
Change from baseline at week 12 end point, LS mean	1.6	2.4	2.6	3.4
95% CI	(0.6, 2.5)	(1.5, 3.4)	(1.7, 3.6)	(2.4, 4.4)
Difference tenapanor vs. placebo, LS mean	–	0.9	1.1	1.8
95% CI	–	(−0.4, 2.1)	(−0.2, 2.3)	(0.5, 3.1)
P value	–	0.187	0.095	0.006
Stool consistencyb
Change from baseline at week 12 end point, LS mean	1.0	1.6	1.9	2.2
95% CI	(0.6, 1.4)	(1.2, 2.0)	(1.5, 2.3)	(1.8, 2.6)
Difference tenapanor vs. placebo, LS mean	–	0.6	0.9	1.2
95% CI	–	(0.1, 1.1)	(0.4, 1.4)	(0.7, 1.7)
P value	–	0.027	<0.001	<0.001
Straining c
Change from baseline at week 12 end point, LS mean	−0.7	−0.8	−1.1	−1.2
95% CI	(−0.9, −0.4)	(−1.0, −0.5)	(−1.3, −0.8)	(−1.4, −0.9)
Difference tenapanor vs. placebo, LS mean	–	−0.1	−0.4	−0.5
95% CI	–	(−0.4, 0.3)	(−0.8, −0.1)	(−0.8, −0.1)
P value	–	0.584	0.020	0.006
IBS severity d
Change from baseline at week 12 end point, LS mean	−1.1	−1.0	−1.1	−1.4
95% CI	(−1.3, −0.9)	(−1.3, −0.8)	(−1.3, −0.8)	(−1.7, −1.2)
Difference tenapanor vs. placebo, LS mean	–	0.1	0.0	−0.3
95% CI	–	(−0.2, 0.4)	(−0.3, 0.3)	(−0.6, −0.0)
P value	–	0.689	0.824	0.024
Constipation severity d
Change from baseline at week 12 end point, LS mean	−1.1	−1.3	−1.3	−1.7
95% CI	(−1.4, −0.9)	(−1.5, −1.1)	(−1.5, −1.1)	(−1.9, −1.4)
Difference tenapanor vs. placebo, LS mean	–	−0.2	−0.2	−0.5
95% CI	–	(−0.5, 0.1)	(−0.5, 0.1)	(−0.8, −0.2)
P value	–	0.233	0.299	<0.001
Degree of relief from IBS e
Week 12 end point, LS mean	3.1	2.9	3.0	2.5
95% CI	(2.8, 3.4)	(2.7, 3.2)	(2.7, 3.2)	(2.2, 2.8)
Difference tenapanor vs. placebo, LS mean	–	−0.2	−0.1	−0.6
95% CI	–	(−0.5, 0.2)	(−0.5, 0.2)	(−0.9, −0.3)
P value	–	0.340	0.436	<0.001
Treatment satisfaction f
Week 12 end point, LS mean	2.9	3.1	3.3	3.7
95% CI	(2.6, 3.2)	(2.8, 3.4)	(3.0, 3.6)	(3.4, 4.0)
Difference tenapanor vs. placebo, LS mean	–	0.3	0.4	0.8
95% CI	–	(−0.1, 0.7)	(0.0, 0.8)	(0.4, 1.2)
P value	–	0.181	0.031	<0.001

ANCOVA, analysis of covariance; ANOVA, analysis of variance; b.i.d., twice daily; BSFS, Bristol Stool Form Scale; CI, confidence interval; CSBM, complete spontaneous bowel movement; IBS, irritable bowel syndrome; IBS-C, constipation-predominant irritable bowel syndrome; LS, least-squares; SBM, spontaneous bowel movement.

^aAssessed daily using a 0–10-point scale: 0=none, 10=very severe. Average weekly score was calculated from scores for all days during a valid week.

^bAssessed using the 7-point BSFS (21). Average weekly score calculated from scores for all SBMs during the week.

^cAssessed for each SBM using a 1–5-point scale: 1=not at all, 5=an extreme amount. Average weekly score calculated from scores for all SBMs during the week.

^dAssessed weekly using a 1–5-point scale: 1=none, 5=very severe.

^eAssessed weekly on a 1–7-point scale: 1=complete relief, 7=as bad as I can imagine.

^fAssessed using a 1–5-point scale: 1=not at all satisfied, 5=very satisfied.

LS means, 95% CIs, and P values were based on an ANCOVA model with treatment and pooled investigator site as factors and baseline as a covariate. Baseline was defined as the average of the respective scores for weeks −1 and −2.

For degree of relief from IBS and treatment satisfaction, LS means, 95% CIs, and P values were based on an ANOVA model with treatment and pooled investigator site as terms.