Trial Outcomes & Findings for Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea in Patients With Inadequate Control of Symptoms With Prior Loperamide Use (NCT NCT02959983)

Last Updated: 2019-02-15

Results Overview

Percentage of primary composite responders is defined as the percentage of participants who meet both of the following daily composite criteria for at least 50% of the days with diary entry: 1)Worst Abdominal Pain (WAP) score improved by ≥40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) Bristol Stool Score (BSS) \<5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

346 participants

Primary outcome timeframe

Baseline, Weeks 1 to 12

Results posted on

2019-02-15

Participant Flow

A total of 660 participants were screened; 346 participants were randomized; 344 participants received at least 1 dose of study drug which comprises the safety population. Randomization and treatment assignment were based on a randomization scheme prepared by Allergan Biostatistics prior to the start of the study.

Participant milestones

Participant milestones
Measure	Eluxadoline Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Overall Study STARTED	172	174
Overall Study COMPLETED	146	149
Overall Study NOT COMPLETED	26	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Eluxadoline Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Overall Study Protocol Violation	0	1
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	12	9
Overall Study Other	1	1
Overall Study Physician Decision	1	0
Overall Study Adverse Event	5	1
Overall Study Withdrawal by Subject	7	12

Baseline Characteristics

Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome With Diarrhea in Patients With Inadequate Control of Symptoms With Prior Loperamide Use

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eluxadoline n=172 Participants Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=174 Participants Placebo matching eluxadoline oral tablets BID with food for 12 weeks.	Total n=346 Participants Total of all reporting groups
Age, Customized <65	158 Participants n=5 Participants	161 Participants n=7 Participants	319 Participants n=5 Participants
Age, Customized ≥65	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Female	124 Participants n=5 Participants	119 Participants n=7 Participants	243 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	55 Participants n=7 Participants	103 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	33 Participants n=5 Participants	41 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	139 Participants n=5 Participants	133 Participants n=7 Participants	272 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	144 Participants n=5 Participants	141 Participants n=7 Participants	285 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	20 Participants n=5 Participants	26 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 1 to 12

Population: The Intent-to-Treat population includes all randomized patients.

Outcome measures

Outcome measures
Measure	Eluxadoline n=172 Participants Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=174 Participants Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Percentage of Participants Who Were Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain And Daily Stool Consistency Scores	22.7 percentage of participants	10.3 percentage of participants

SECONDARY outcome

Timeframe: Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)

Population: The Intent-to-Treat population includes all randomized patients.

Percentage of stool consistency responders is defined as the percentage of participants who meet the daily stool consistency response criteria: BSS \<5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline for ≥50% of days with daily patient diary entries over a certain time period. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool). A participant must have had a minimum of 20 days of diary entries over any 4-week interval.

Outcome measures

Outcome measures
Measure	Eluxadoline n=172 Participants Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=174 Participants Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Percentage of Stool Consistency Responders Overall Weeks 1 to 12	27.9 Percentage of Participants	16.7 Percentage of Participants
Percentage of Stool Consistency Responders Weeks 1 to 4	24.4 Percentage of Participants	12.6 Percentage of Participants
Percentage of Stool Consistency Responders Weeks 5 to 8	30.8 Percentage of Participants	20.1 Percentage of Participants
Percentage of Stool Consistency Responders Weeks 9 to 12	29.7 Percentage of Participants	25.3 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1 to 12 and 4-week intervals (Weeks 1 to 4, Weeks 5 to 8 and Weeks 9 to 12)

Population: The Intent-to-Treat population includes all randomized patients.

Percentage of pain responders is defined as the percentage of participants who meet the daily pain response criteria: WAP score improved by ≥40% compared to Baseline for ≥50% of days with diary entries over a certain time period. The participant records their WAP score in the past 24 hours each day in a daily diary where: 0=no pain to 10=worst imaginable pain. A participant must have had a minimum of 20 days of diary entries over any 4-week interval.

Outcome measures

Outcome measures
Measure	Eluxadoline n=172 Participants Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=174 Participants Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Percentage of Pain Responders Overall Weeks 1 to 12	43.6 Percentage of Participants	31.0 Percentage of Participants
Percentage of Pain Responders Weeks 1 to 4	30.2 Percentage of Participants	25.9 Percentage of Participants
Percentage of Pain Responders Weeks 5 to 8	45.9 Percentage of Participants	31.6 Percentage of Participants
Percentage of Pain Responders Weeks 9 to 12	44.8 Percentage of Participants	35.1 Percentage of Participants

SECONDARY outcome

Timeframe: Weeks 1 to 4, 5 to 8, and 9 to 12

Population: The Intent-to-Treat population includes all randomized patients.

Percentage of monthly composite responders is defined as the percentage of participants who meet the daily composite response criteria for at least 50% of days with diary entry for a minimum of 20 days during each 4-week interval (weeks 1 to 4, 5 to 8, and 9 to 12). Composite response includes both of the following criteria: 1) WAP score improved by ≥40% compared to Baseline. The participant records their WAP score in the past 24 hours each day in a daily patient diary where: 0=no pain to 10=worst imaginable pain. 2) BSS \<5; or the absence of a bowel movement if accompanied by ≥40% improvement in WAP compared to Baseline. The participant records their stool consistency each day in a daily patient diary using the BSS on a scale from 1 (hard stool) to 7 (watery stool).

Outcome measures

Outcome measures
Measure	Eluxadoline n=172 Participants Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=174 Participants Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Percentage of Monthly Composite Responders Weeks 1-4	14 Percentage of Participants	6.9 Percentage of Participants
Percentage of Monthly Composite Responders Weeks 5-8	26.7 Percentage of Participants	14.9 Percentage of Participants
Percentage of Monthly Composite Responders Weeks 9-12	30.8 Percentage of Participants	16.7 Percentage of Participants

Adverse Events

Eluxadoline

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Eluxadoline n=171 participants at risk Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=173 participants at risk Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Gastrointestinal disorders Pancreatic mass	0.58% 1/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.00% 0/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Infections and infestations Cellulitis	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Infections and infestations Pneumonia	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Cardiac disorders Cardiac failure congestive	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Reproductive system and breast disorders Endometriosis	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.
Reproductive system and breast disorders Pelvic pain	0.00% 0/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	0.58% 1/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.

Other adverse events

Other adverse events
Measure	Eluxadoline n=171 participants at risk Eluxadoline 100 mg oral tablets twice daily (BID) with food for 12 weeks.	Placebo n=173 participants at risk Placebo matching eluxadoline oral tablets BID with food for 12 weeks.
Gastrointestinal disorders Nausea	5.8% 10/171 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.	2.9% 5/173 • Up to 12 weeks The Safety Population will include all patients enrolled who received at least 1 dose of study drug. Safety data will be analyzed using the safety population.

Additional Information

Therapeutic Area Head

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER