A Study to Evaluate Safety and Efficacy of Telotristat Etiprate (LX1606) in Participants With Acute, Mild to Moderate Ulcerative Colitis

• Telotristat Etiprate (Drug): 500 mg telotristat etiprate (LX1606) administered orally.
• Placebo (Drug): Matching placebo administered orally.

Primary outcomes

• Number of Participants Experiencing a Treatment Emergent Adverse Event [8 weeks]

Secondary outcomes

• Number of Participants Achieving Clinical Response [Baseline to 8 weeks]: Clinical response is defined as a decrease in the total modified Mayo score from baseline of ≥3 or a ≥30% decrease in the total modified Mayo score from baseline, along with a decrease in the rectal bleeding score ≥1 or an absolute rectal bleeding score ≤1 at Week 8. A modified Mayo score was used to evaluate disease activity using 4 components, including stool frequency, rectal bleeding, endoscopy, and physician assessment. Components = Stool frequency score 0-3 (normal- >4 stools/day more than normal), rectal bleeding score 0-3 (none-passing blood alone), mucosal appearance at endoscopy 0-3 (normal-severe disease), physician rating of disease activity 0-3 (normal-severe). The total Modified Mayo score ranges from 0 to 12, with higher scores indicating greater disease severity.
• Number of Participants Achieving Clinical Remission [Baseline to 8 weeks]: Clinical remission is defined as a total modified Mayo score ≤2 with no individual score >1 at Week 8. A modified Mayo score was used to evaluate disease activity using 4 components, including stool frequency, rectal bleeding, endoscopy, and physician assessment. Components = Stool frequency score 0-3 (normal- >4 stools/day more than normal), rectal bleeding score 0-3 (none-passing blood alone), mucosal appearance at endoscopy 0-3 (normal-severe disease), physician rating of disease activity 0-3 (normal-severe). The total Modified Mayo score ranges from 0 to 12, with higher scores indicating greater disease severity.
• Change From Baseline in Total Modified Mayo Score [Baseline to 8 weeks]: A modified Mayo score was used to evaluate disease activity using 4 components, including stool frequency, rectal bleeding, endoscopy, and physician assessment. Components = Stool frequency score 0-3 (normal- >4 stools/day more than normal), rectal bleeding score 0-3 (none-passing blood alone), mucosal appearance at endoscopy 0-3 (normal-severe disease), physician rating of disease activity 0-3 (normal-severe). The total Modified Mayo score ranges from 0 to 12, with higher scores indicating greater disease severity.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* Diagnosis of ulcerative colitis of at least 6 months duration
* Disease extends at least 15 cm proximally from the anal verge, documented within the past 3 years
* Flare occurs on 5-aminosalicylic acid (5-ASA)/mesalamine therapy and subject is willing to remain on a stable dose for the duration of the study
* Age ≥18 and <70 years of age
* Able and willing to provide written informed consent

Exclusion Criteria:

* Prior terminal ileum or colonic surgery, except appendectomy or hemorrhoid surgery
* Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease
* Clinical signs of fulminant colitis or toxic megacolon
* History of dysplasia associated lesion or mass (DALM)
* Subjects who have had surgery for ulcerative colitis, or in the opinion of the investigator, are likely to require surgery for ulcerative colitis during the study
* History of primary sclerosing cholangitis
* Any physical or laboratory abnormality deemed by the investigator as clinically significant
* Major surgery within 60 days of Screening
* Use of any investigational agent within 30 days of Screening or any therapeutic protein or antibody within 90 days of Screening

Participant flow

Outcome results

• Number of Participants Experiencing a Treatment Emergent Adverse Event (Primary), Number, participants: Placebo 3; Low Dose LX1606 9; High Dose Telotristat Etiprate 10
• Number of Participants Achieving Clinical Response (Secondary), Number, participants: Placebo 4; Low Dose Telotristat Etiprate 8; High Dose Telotristat Etiprate 8
• Number of Participants Achieving Clinical Remission (Secondary), Number, participants: Placebo 2; Low Dose Telotristat Etiprate 2; High Dose Telotristat Etiprate 3
• Change From Baseline in Total Modified Mayo Score (Secondary), Mean, units on a scale: Placebo -2.38 +/- 2.973; Low Dose Telotristat Etiprate -1.89 +/- 2.865; High Dose Telotristat Etiprate -2.53 +/- 2.389

Adverse events

Time frame: 10 weeks

Serious adverse events by term

Other adverse events by term

• Doug Fleming, MD, Study director, Lexicon Pharmaceuticals, Inc.