Table 2. Summary of the clinical trials in chronic constipation.

[<3 spontaneous bowel movements (SBM)/week + lumpy and or hard stools, straining and sensation of incomplete evacuation during defecation; pain not a predominant symptom]

Author, year	Dose (mg/day)	Simren et al. 2011 [50]	Wong et al. 2011 [51]	Chey et al. 2011 [52]	Nakajima et al. 2018 [53]	Nakajima et al. 2018 - 2wk RCT [54]	Nakajima et al. 2018 - 52wk open label [54]
N (F/M)		30 (23/7)	36 (36/0)	190 (170/20)	163 (143/20)	132 (109/23)	340 (283/57)
Study duration, wk		2	2	8	2	2	52
Location of Study		Sweden	USA		Japan
Primary Outcome		Safety	Colon transit	SBM	SBM at wk1	SBM at wk1	Safety, SBM and satisfaction over 52 wks
BSFS (1-7 scale)	3	↑
	5			↑ 1	↑ 1.3
	10	↑		↑ 1	↑ 1.7	↑ 1.8
	15		↑ 1.3	↑ 1	↑ 2.0
	20		↑ 1.8
Stool (SBM) #/ day	3	↑
	5			↑ 2.5	↑ 1.7		↑ 3.3*
	10	↑		↑ 4.0	↑ 4.1	↑ 6.4	↑ 3.3*
	15		↑ 0.5	↑ 5.4	↑ 3.8		↑ 3.3*
	20		↑ 1.17
AE: Abdo pain	3
	5			10%	23%		24%*
	10			11%	26%	19%	24%*
	15		36%	27%	12%		24%*
	20		50%
AE: Diarrhea	3
	5			8%	9%		15%*
	10			6%	5%	13%	15%*
	15		9%	13%	7%		15%*
	20		36%

^*Refers to the average response over 5 mg, 10 mg, and 15 mg. There were equal proportions of patients with each dose listed.