Table VI.

Probabilities Predicted from PK/Efficacy Models and PK/Safety Models

Probabilities of occurrence of spontaneous bowel movement (SBM) respondera
Study No.	Placebo		Dose: 0.1 mg				Dose: 0.2 mg		Dose: 0.4 mg
	AUCss	Probability	AUCss		Probability		AUCss	Probability	AUCss	Probability
1107 V9221 (Phase 2b)	0.00	0.422	11.06		0.474		22.11	0.527	44.22	0.630
1314 V9231 and 1315 V9232 (Phase 3)	0.00	0.369	13.75		0.433		27.50	0.499	55.00	0.630
Probabilities of occurrence of gastrointestinal disordersb
Study No.	Severity of Gastrointestinal Disorders		Placebo		Dose: 0.1 mg		Dose: 0.2 mg		Dose: 0.4 mg
			AUCss	Probability	AUCss	Probability	AUCss	Probability	AUCss	Probability
1107 V9221 (Phase 2b)	Mild, Moderate, Severe		0.00	0.146	11.06	0.195	22.11	0.254	44.22	0.403
	Moderate, Severe		0.00	0.060	11.06	0.078	22.11	0.101	44.22	0.165
1314 V9231 and 1315 V9232 (Phase 3)	Mild, Moderate, Severe		0.00	0.151	13.75	0.172	27.50	0.193	55.00	0.242
	Moderate, Severe		0.00	0.060	13.75	0.071	27.50	0.083	55.00	0.113
	Severe		0.00	0.012	13.75	0.015	27.50	0.018	55.00	0.027

^aProbability (SBM Responder) = 1 / [1 + exp. (− a - b × AUC_ss)]

^bProbability (Gastrointestinal Disorders) = 1 / [1 + exp. (− a - b × AUC_ss)]

AUC_ss in the placebo group was treated as zero. AUC_ss in 0.1 mg group was assumed to be half the AUC_ss in 0.2 mg group

AUC_ss in 0.4 mg group was assumed to be double the AUC_ss in 0.2 mg group

Unit of AUC_ss: ng*hr/ml

AUC in the placebo group was treated as zero. AUC in 0.1 mg group was assumed to be half the AUC in 0.2 mg group

AUC in 0.4 mg group was assumed to be double the AUC in 0.2 mg group

Unit of AUC: ng*hr/ml