Ulcerative Colitis
Conditions
Brief summary
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.
Interventions
500 mg telotristat etiprate (LX1606) administered orally.
DRUGPlacebo
Matching placebo administered orally.
Sponsors
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Experiencing a Treatment Emergent Adverse Event | 8 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Lithuania, Poland, Slovakia, United States
Participant flow
Recruitment details
Up to 60 participants were to be enrolled and treated in the blinded Treatment period across 24 US and international sites. The recruitment period lasted approximately 10 months.
Pre-assignment details
The study consisted of an approximately 15 days Screening period prior to the blinded Treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo administered orally. | 10 |
| Low Dose Telotristat Etiprate 500 mg telotristat etiprate (LX1606) administered orally once daily (QD). | 24 |
| High Dose Telotristat Etiprate 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID) | 24 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 |
| Overall Study | Consent withdrawn | 0 | 2 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Treatment Failure | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Low Dose Telotristat Etiprate | High Dose Telotristat Etiprate | Total |
|---|---|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 16.16 | 45.5 years STANDARD_DEVIATION 12.49 | 41.7 years STANDARD_DEVIATION 12.69 | 42.8 years STANDARD_DEVIATION 13.23 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 24 Participants | 22 Participants | 56 Participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 17 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 10 | 9 / 24 | 2 / 24 |
| serious Total, serious adverse events | 1 / 10 | 3 / 24 | 2 / 24 |
Outcome results
Primary
Number of Participants Experiencing a Treatment Emergent Adverse Event
Time frame: 8 weeks
Population: Safety population included all treated participants who had taken any fraction of a study drug dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing a Treatment Emergent Adverse Event | 3 participants |
| Low Dose LX1606 | Number of Participants Experiencing a Treatment Emergent Adverse Event | 9 participants |
| High Dose Telotristat Etiprate | Number of Participants Experiencing a Treatment Emergent Adverse Event | 10 participants |
Secondary
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.
Time frame: Baseline to 8 weeks
Population: Participants from the ITT Population, all randomly assigned participants, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Modified Mayo Score | -2.38 units on a scale | Standard Deviation 2.973 |
| Low Dose LX1606 | Change From Baseline in Total Modified Mayo Score | -1.89 units on a scale | Standard Deviation 2.865 |
| High Dose Telotristat Etiprate | Change From Baseline in Total Modified Mayo Score | -2.53 units on a scale | Standard Deviation 2.389 |
Secondary
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.
Time frame: Baseline to 8 weeks
Population: ITT Population included all randomly assigned participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Achieving Clinical Remission | 2 participants |
| Low Dose LX1606 | Number of Participants Achieving Clinical Remission | 2 participants |
| High Dose Telotristat Etiprate | Number of Participants Achieving Clinical Remission | 3 participants |
Secondary
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.
Time frame: Baseline to 8 weeks
Population: Intent-to-treat (ITT) Population included all randomly assigned participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Achieving Clinical Response | 4 participants |
| Low Dose LX1606 | Number of Participants Achieving Clinical Response | 8 participants |
| High Dose Telotristat Etiprate | Number of Participants Achieving Clinical Response | 8 participants |