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

Study Overview
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Brief Summary
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This is a multicenter, placebo-controlled, parallel-group, pilot study to evaluate safety and preliminary effectiveness of two blinded dose levels of telotristat etiprate (LX1606) in participants with acute, mild to moderate ulcerative colitis on 5-aminosalicylic acid/mesalamine therapy.

Official Title
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Phase 2 Assessment of the Relationship Between Serotonin and Efficacy in Ulcerative Colitis: A Multi-Center Randomized, Double Blind, Placebo-Controlled, Pilot Study to Evaluate Safety and Preliminary Efficacy of Orally Administered LX1606 in Subjects With Acute, Mild to Moderate Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Telotristat Etiprate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Telotristat Etiprate<br>500 mg telotristat etiprate (LX1606) administered orally once daily (QD). | Drug: Telotristat Etiprate<br>* 500 mg telotristat etiprate (LX1606) administered orally.<br>|
| Experimental: High Dose Telotristat Etiprate<br>500 mg telotristat etiprate (LX1606) administered orally three times daily (TID). | Drug: Telotristat Etiprate<br>* 500 mg telotristat etiprate (LX1606) administered orally.<br>|
| Placebo Comparator: Placebo<br>Matching placebo administered orally. | Drug: Placebo<br>* Matching placebo administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing a Treatment Emergent Adverse Event |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Clinical Response | 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. | Baseline to 8 weeks | 
| Number of Participants Achieving Clinical Remission | 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. | Baseline to 8 weeks | 
| Change From Baseline in Total Modified Mayo Score | 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. | Baseline to 8 weeks |