Trial Outcomes & Findings for A Study to Evaluate Safety and Efficacy of Telotristat Etiprate (LX1606) in Participants With Acute, Mild to Moderate Ulcerative Colitis (NCT NCT01456052)

NCT ID: NCT01456052

Last Updated: 2019-05-23

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 59 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2019-05-23

Participant Flow

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.

The study consisted of an approximately 15 days Screening period prior to the blinded Treatment period.

Participant milestones

Measure	Placebo Placebo: Matching placebo administered orally.	Low Dose Telotristat Etiprate 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Overall Study STARTED	10	25	24
Overall Study COMPLETED	8	20	19
Overall Study NOT COMPLETED	2	5	5

Reasons for withdrawal

Measure	Placebo Placebo: Matching placebo administered orally.	Low Dose Telotristat Etiprate 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Overall Study Adverse Event	1	1	2
Overall Study Consent withdrawn	0	2	1
Overall Study Protocol Violation	0	1	0
Overall Study Physician Decision	1	0	1
Overall Study Treatment Failure	0	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=10 Participants Matching placebo administered orally.	Low Dose Telotristat Etiprate n=24 Participants 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=24 Participants 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID)	Total n=58 Participants Total of all reporting groups
Age, Continuous	39.2 years STANDARD_DEVIATION 16.16 • n=5 Participants	45.5 years STANDARD_DEVIATION 12.49 • n=7 Participants	41.7 years STANDARD_DEVIATION 12.69 • n=5 Participants	42.8 years STANDARD_DEVIATION 13.23 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	12 Participants n=7 Participants	7 Participants n=5 Participants	23 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants	35 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	24 Participants n=7 Participants	22 Participants n=5 Participants	56 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Safety population included all treated participants who had taken any fraction of a study drug dose.

Outcome measures

Measure	Placebo n=10 Participants Matching placebo administered orally.	Low Dose LX1606 n=24 Participants 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=24 Participants 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Number of Participants Experiencing a Treatment Emergent Adverse Event	3 participants	9 participants	10 participants

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Intent-to-treat (ITT) Population included all randomly assigned participants.

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.

Outcome measures

Measure	Placebo n=10 Participants Matching placebo administered orally.	Low Dose LX1606 n=25 Participants 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=24 Participants 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Number of Participants Achieving Clinical Response	4 participants	8 participants	8 participants

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: ITT Population included all randomly assigned participants.

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.

Outcome measures

Measure	Placebo n=10 Participants Matching placebo administered orally.	Low Dose LX1606 n=25 Participants 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=24 Participants 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Number of Participants Achieving Clinical Remission	2 participants	2 participants	3 participants

SECONDARY outcome

Timeframe: Baseline to 8 weeks

Population: Participants from the ITT Population, all randomly assigned participants, with data available for analysis.

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.

Outcome measures

Measure	Placebo n=8 Participants Matching placebo administered orally.	Low Dose LX1606 n=19 Participants 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=19 Participants 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Change From Baseline in Total Modified Mayo Score	-2.38 units on a scale Standard Deviation 2.973	-1.89 units on a scale Standard Deviation 2.865	-2.53 units on a scale Standard Deviation 2.389

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Low Dose Telotristat Etiprate

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

High Dose Telotristat Etiprate

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=10 participants at risk Matching placebo administered orally.	Low Dose Telotristat Etiprate n=24 participants at risk 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=24 participants at risk 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Gastrointestinal disorders Colitis ulcerative	10.0% 1/10 • Number of events 1 • 10 weeks	12.5% 3/24 • Number of events 3 • 10 weeks	0.00% 0/24 • 10 weeks
Infections and infestations Appendicitis	0.00% 0/10 • 10 weeks	0.00% 0/24 • 10 weeks	4.2% 1/24 • Number of events 1 • 10 weeks
Blood and lymphatic system disorders Iron deficiency anemia	0.00% 0/10 • 10 weeks	0.00% 0/24 • 10 weeks	4.2% 1/24 • Number of events 1 • 10 weeks

Other adverse events

Measure	Placebo n=10 participants at risk Matching placebo administered orally.	Low Dose Telotristat Etiprate n=24 participants at risk 500 mg telotristat etiprate (LX1606) administered orally once daily (QD).	High Dose Telotristat Etiprate n=24 participants at risk 500 mg telotristat etiprate (LX1606) administered orally three times daily (TID).
Gastrointestinal disorders Colitis ulcerative	10.0% 1/10 • Number of events 1 • 10 weeks	8.3% 2/24 • Number of events 2 • 10 weeks	4.2% 1/24 • Number of events 1 • 10 weeks
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • 10 weeks	8.3% 2/24 • Number of events 2 • 10 weeks	0.00% 0/24 • 10 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/10 • 10 weeks	8.3% 2/24 • Number of events 2 • 10 weeks	0.00% 0/24 • 10 weeks
Gastrointestinal disorders Dyspepsia	0.00% 0/10 • 10 weeks	8.3% 2/24 • Number of events 2 • 10 weeks	0.00% 0/24 • 10 weeks
Infections and infestations Nasopharyngitis	10.0% 1/10 • Number of events 1 • 10 weeks	0.00% 0/24 • 10 weeks	4.2% 1/24 • Number of events 1 • 10 weeks
Infections and infestations Sinusitis	0.00% 0/10 • 10 weeks	8.3% 2/24 • Number of events 2 • 10 weeks	0.00% 0/24 • 10 weeks
Infections and infestations Influenza	10.0% 1/10 • Number of events 1 • 10 weeks	0.00% 0/24 • 10 weeks	0.00% 0/24 • 10 weeks
Nervous system disorders Dizziness	10.0% 1/10 • Number of events 1 • 10 weeks	0.00% 0/24 • 10 weeks	0.00% 0/24 • 10 weeks
Nervous system disorders Memory impairment	10.0% 1/10 • Number of events 1 • 10 weeks	0.00% 0/24 • 10 weeks	0.00% 0/24 • 10 weeks

Additional Information

Manager of Regulatory Affairs

Lexicon Pharmaceuticals, Inc.

Phone: 281-863-3260

Email: plogan@lexpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution must provide any proposed publication or presentation to Sponsor for Sponsor's review, comment and approval at least sixty (60) days prior to the proposed submission for publication date or the proposed presentation date. Sponsor shall have the right to have deleted from the final version of the publication any information to which Sponsor objects, any Confidential Information, proprietary information or patentable subject matter.
• Publication restrictions are in place

Restriction type: OTHER