Table 4.

Adverse events of special interest.

AESI category preferred term, n (%)		DBT			OLE
		Placebo tid (n = 26)	Telotristat ethyl 250 mg tid (n = 25)	Telotristat ethyl 500 mg tid (n = 25)	Telotristat ethyl 500 mg tid (n = 67)
Gastrointestinal-related TEAE
Abdominal pain	Total	4 (15.4)	8 (32.0)	1 (4.0)	12 (17.9)
	Mild	1 (3.8)	3 (12.0)	0	5 (7.5)
	Moderate	3 (11.5)	3 (12.0)	0	6 (9.0)
	Severe	0	2 (8.0)	1 (4.0)	1 (1.5)
Diarrhea	Total	5 (19.2)	4 (16.0)	2 (8.0)	9 (13.4)
	Mild	2 (7.7)	2 (8.0)	1 (4.0)	3 (4.5)
	Moderate	3 (11.5)	2 (8.0)	1 (4.0)	4 (6.0)
	Severe	0	0	0	2 (3.0)
Nausea	Total	4 (15.4)	3 (12.0)	2 (8.0)	14 (20.9)
	Mild	4 (15.4)	2 (8.0)	2 (8.0)	8 (11.9)
	Moderate	0	1 (4.0)	0	5 (7.5)
	Severe	0	0	0	1 (1.5)
Constipation	Total	1 (3.8)	4 (16.0)	3 (12.0)	8 (11.9)
	Mild	0	3 (12.0)	3 (12.0)	5 (7.5)
	Moderate	1 (3.8)	1 (4.0)	0	2 (3.0)
	Severe	0	0	0	1 (1.5)
Abdominal pain upper	Total	3 (11.5)	1 (4.0)	2 (8.0)	5 (7.5)
	Mild	2 (7.7)	0	2 (8.0)	3 (4.5)
	Moderate	1 (3.8)	1 (4.0)	0	2 (3.0)
	Severe	0	0	0	0
Abdominal distension	Total	0	3 (12.0)	1 (4.0)	4 (6.0)
	Mild	0	2 (8.0)	1 (4.0)	4 (6.0)
	Moderate	0	1 (4.0)	0	0
	Severe	0	0	0	0
Abdominal discomfort	Total	1 (3.8)	0	1 (4.0)	1 (1.5)
	Mild	1 (3.8)	0	1 (4.0)	1 (1.5)
	Moderate	0	0	0	0
	Severe	0	0	0	0
Flatulence	Total	0	1 (4.0)	1 (4.0)	2 (3.0)
	Mild	0	1 (4.0)	1 (4.0)	1 (1.5)
	Moderate	0	0	0	1 (1.5)
	Severe	0	0	0	0
Abdominal tenderness	Total	0	0	1 (4.0)	0
	Mild	0	0	1 (4.0)	0
	Moderate	0	0	0	0
	Severe	0	0	0	0
Frequent bowel movements	Total	0	1 (4.0)	0	0
	Mild	0	0	0	0
	Moderate	0	1 (4.0)	0	0
	Severe	0	0	0	0
Abdominal pain lower	Total	0	0	0	1 (1.5)
	Mild	0	0	0	0
	Moderate	0	0	0	1 (1.5)
	Severe	0	0	0	0
Gastrointestinal pain	Total	0	0	0	1 (1.5)
	Mild	0	0	0	1 (1.5)
	Moderate	0	0	0	0
	Severe	0	0	0	0
Vomiting	Total	1 (3.8)	1 (4.0)	1 (4.0)	7 (10.4)
	Mild	0	1 (4.0)	0	4 (6.0)
	Moderate	1 (3.8)	0	1 (4.0)	2 (3.0)
	Severe	0	0	0	1 (1.5)
Depression-related TEAE
Depressed mood	Total	2 (7.7)	1 (4.0)	0	2 (3.0)
	Mild	2 (7.7)	1 (4.0)	0	2 (3.0)
	Moderate	0	0	0	0
	Severe	0	0	0	0
Decreased interest	Total	1 (3.8)	0	0	0
	Mild	1 (3.8)	0	0	0
	Moderate	0	0	0	0
	Severe	0	0	0	0
Depression	Total	0	0	1 (4.0)	8 (11.9)
	Mild	0	0	0	4 (6.0)
	Moderate	0	0	1 (4.0)	4 (6.0)
	Severe	0	0	0	0
Hepatic-enzyme-related TEAE
Elevated gamma-glutamyl transferase	Total	0	1 (4.0)	1 (4.0)	4 (6.0)
	Mild	0	1 (4.0)	0	1 (1.5)
	Moderate	0	0	1 (4.0)	1 (1.5)
	Severe	0	0	0	2 (3.0)
Elevated alanine aminotransferase	Total	0	1 (4.0)	0	3 (4.5)
	Mild	0	1 (4.0)	0	2 (3.0)
	Moderate	0	0	0	0
	Severe	0	0	0	1 (1.5)
Liver function test abnormal	Total	0	0	1 (4.0)	1 (1.5)
	Mild	0	0	1 (4.0)	0
	Moderate	0	0	0	1 (1.5)
	Severe	0	0	0	0
Elevated aspartate aminotransferase	Total	0	0	0	3 (4.5)
	Mild	0	0	0	2 (3.0)
	Moderate	0	0	0	0
	Severe	0	0	0	1 (1.5)
Blood alkaline phosphatase increased	Total	0	0	0	2 (3.0)
	Mild	0	0	0	1 (1.5)
	Moderate	0	0	0	1 (1.5)
	Severe	0	0	0	0
Hepatic enzyme increased	Total	0	0	0	2 (3.0)
	Mild	0	0	0	1 (1.5)
	Moderate	0	0	0	1 (1.5)
	Severe	0	0	0	0

AESI, adverse event of special interest; DBT, double-blind treatment; OLE, open-label extension; TEAE, treatment-emergent adverse event; tid, 3 times per day.