Irritable Bowel Syndrome
Conditions
Brief summary
This study will explore the safety and effectiveness of different doses of AGN 203818 in relieving Irritable Bowel Syndrome pain. The study is being conducted in 2 parts. Part A enrolled 213 pts dosed with either 3, 20, 60 mg AGN 203818 or placebo over 4 week treatment duration. Part B will enroll 320 pts and dose with either 60, 100, 160 mg BID AGN 203818 or placebo over 12 week treatment duration.
Interventions
DRUGAGN 203818
Part A: 3 mg AGN203818 capsule every 12 hours for 4 weeks
DRUGplacebo
Part A: placebo capsule every 12 hours for 4 weeks
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Irritable Bowel Syndrome * Moderate or severe IBS pain
Exclusion criteria
* Any other uncontrolled disease * Pregnant or nursing females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Baseline, Week 4 | Change from baseline in mean highest-average-pain score at Week 4. The mean highest-average-pain score was the average of the 7 highest daily-average-pain scores obtained over the 14 days prior to the Week 4 visit. Patients recorded their daily-average-pain on an 11-point scale (where 0 equals no pain and 10 equals worst pain imaginable). A negative number change from baseline represents a decrease in average pain (improvement). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4 | Week 4 | Percentage of patients who rated their condition as improved on the SGIC at week 4. The SGIC score was assessed using a 7-point scale (score of 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). Patients self-evaluated their overall change in symptoms (relief from symptoms of abdominal discomfort, pain, and altered bowel habits). An improved condition was defined as a score of 1, 2, or 3. |
| Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4 | Week 4 | Percentage of patients who experienced AR-IBS at week 4. The AR-IBS is a self-evaluation by the patient of their perception of adequate relief of IBS pain over the last 7 days following treatment as compared to IBS pain before receiving treatment. Patients respond with either a Yes or No, where Yes indicated adequate relief of pain and No indicated no relief from pain. |
| Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | Baseline, Week 4 | Change from baseline in the frequency of bowel movements per day using the BSS. The BSS categorizes stool based on the patient's description of its consistency. Patients are classified into 3 IBS subtypes according to their predominant stool patterns (C=constipation; D=diarrhea; M=mixed). A positive change from baseline in the IBS-C indicates improvement and a negative change from baseline in the IBS-D and IBS-M indicates improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AGN 203818 60 mg Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks | 53 |
| AGN 203818 20 mg Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks | 53 |
| AGN 203818 3 mg Part A: AGN 203818 3 mg capsule every 12 hours for 4 weeks | 53 |
| Placebo Part A: Placebo capsule every 12 hours for 4 weeks | 54 |
| Total | 213 |
Baseline characteristics
| Characteristic | AGN 203818 60 mg | AGN 203818 20 mg | AGN 203818 3 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Customized 18 to 64 years | 48 participants | 48 participants | 50 participants | 54 participants | 200 participants |
| Age, Customized >=65 years | 5 participants | 5 participants | 3 participants | 0 participants | 13 participants |
| Sex: Female, Male Female | 53 Participants | 53 Participants | 53 Participants | 54 Participants | 213 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 52 / 53 | 48 / 53 | 28 / 52 | 39 / 54 |
| serious Total, serious adverse events | 8 / 53 | 0 / 53 | 2 / 52 | 1 / 54 |
Outcome results
Primary
Change From Baseline in Mean Highest-Average-Pain Score at Week 4
Change from baseline in mean highest-average-pain score at Week 4. The mean highest-average-pain score was the average of the 7 highest daily-average-pain scores obtained over the 14 days prior to the Week 4 visit. Patients recorded their daily-average-pain on an 11-point scale (where 0 equals no pain and 10 equals worst pain imaginable). A negative number change from baseline represents a decrease in average pain (improvement).
Time frame: Baseline, Week 4
Population: Modified Intent-To-Treat (m-ITT). The m-ITT population included all patients who started the study (randomized), who received the study medication and had at least one post-baseline mean highest-average-pain score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AGN 203818 60 mg | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Baseline | 5.8 Scores on a Scale | Standard Deviation 1.18 |
| AGN 203818 60 mg | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Change from Baseline at Week 4 | -2.3 Scores on a Scale | Standard Deviation 2.07 |
| AGN 203818 20 mg | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Baseline | 5.7 Scores on a Scale | Standard Deviation 1.09 |
| AGN 203818 20 mg | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Change from Baseline at Week 4 | -1.9 Scores on a Scale | Standard Deviation 1.81 |
| AGN 203818 3 mg | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Change from Baseline at Week 4 | -1.7 Scores on a Scale | Standard Deviation 1.46 |
| AGN 203818 3 mg | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Baseline | 6.0 Scores on a Scale | Standard Deviation 1.48 |
| Placebo | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Change from Baseline at Week 4 | -2.2 Scores on a Scale | Standard Deviation 2.15 |
| Placebo | Change From Baseline in Mean Highest-Average-Pain Score at Week 4 | Baseline | 6.0 Scores on a Scale | Standard Deviation 1.15 |
Secondary
Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS)
Change from baseline in the frequency of bowel movements per day using the BSS. The BSS categorizes stool based on the patient's description of its consistency. Patients are classified into 3 IBS subtypes according to their predominant stool patterns (C=constipation; D=diarrhea; M=mixed). A positive change from baseline in the IBS-C indicates improvement and a negative change from baseline in the IBS-D and IBS-M indicates improvement.
Time frame: Baseline, Week 4
Population: Modified Intent-To-Treat (m-ITT). The m-ITT population included all patients who started the study (randomized), who received the study medication and had at least one post-baseline mean highest-average-pain score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AGN 203818 60 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Baseline | 1.3 Bowel Movements (Stools) Per Day | Standard Deviation 0.79 |
| AGN 203818 60 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Change from Baseline at Week 4 | -0.3 Bowel Movements (Stools) Per Day | Standard Deviation 1.1 |
| AGN 203818 60 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Baseline | 0.9 Bowel Movements (Stools) Per Day | Standard Deviation 0.43 |
| AGN 203818 60 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Baseline | 3.5 Bowel Movements (Stools) Per Day | Standard Deviation 1.59 |
| AGN 203818 60 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Change from Baseline at Week 4 | -0.2 Bowel Movements (Stools) Per Day | Standard Deviation 0.56 |
| AGN 203818 60 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Change from Baseline at Week 4 | 0.1 Bowel Movements (Stools) Per Day | Standard Deviation 0.63 |
| AGN 203818 20 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Change from Baseline at Week 4 | -0.8 Bowel Movements (Stools) Per Day | Standard Deviation 1.33 |
| AGN 203818 20 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Baseline | 1.1 Bowel Movements (Stools) Per Day | Standard Deviation 0.47 |
| AGN 203818 20 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Baseline | 1.4 Bowel Movements (Stools) Per Day | Standard Deviation 0.78 |
| AGN 203818 20 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Change from Baseline at Week 4 | -0.3 Bowel Movements (Stools) Per Day | Standard Deviation 0.68 |
| AGN 203818 20 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Change from Baseline at Week 4 | 0.1 Bowel Movements (Stools) Per Day | Standard Deviation 0.72 |
| AGN 203818 20 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Baseline | 3.6 Bowel Movements (Stools) Per Day | Standard Deviation 2.95 |
| AGN 203818 3 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Baseline | 1.0 Bowel Movements (Stools) Per Day | Standard Deviation 0.71 |
| AGN 203818 3 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Change from Baseline at Week 4 | 0.0 Bowel Movements (Stools) Per Day | Standard Deviation 0.32 |
| AGN 203818 3 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Baseline | 4.3 Bowel Movements (Stools) Per Day | Standard Deviation 2.48 |
| AGN 203818 3 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Change from Baseline at Week 4 | -0.7 Bowel Movements (Stools) Per Day | Standard Deviation 1.09 |
| AGN 203818 3 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Change from Baseline at Week 4 | -0.1 Bowel Movements (Stools) Per Day | Standard Deviation 0.99 |
| AGN 203818 3 mg | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Baseline | 2.7 Bowel Movements (Stools) Per Day | Standard Deviation 1.64 |
| Placebo | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Change from Baseline at Week 4 | 0.1 Bowel Movements (Stools) Per Day | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-C) Baseline | 0.8 Bowel Movements (Stools) Per Day | Standard Deviation 0.57 |
| Placebo | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Change from Baseline at Week 4 | 0.2 Bowel Movements (Stools) Per Day | Standard Deviation 0.86 |
| Placebo | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Baseline | 3.4 Bowel Movements (Stools) Per Day | Standard Deviation 1.88 |
| Placebo | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-D) Change from Baseline at Week 4 | -0.4 Bowel Movements (Stools) Per Day | Standard Deviation 1.46 |
| Placebo | Change From Baseline in Frequency of Bowel Movements at Week 4 Using the Bristol Stool Scale (BSS) | (IBS-M) Baseline | 1.8 Bowel Movements (Stools) Per Day | Standard Deviation 1.41 |
Secondary
Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4
Percentage of patients who experienced AR-IBS at week 4. The AR-IBS is a self-evaluation by the patient of their perception of adequate relief of IBS pain over the last 7 days following treatment as compared to IBS pain before receiving treatment. Patients respond with either a Yes or No, where Yes indicated adequate relief of pain and No indicated no relief from pain.
Time frame: Week 4
Population: Modified Intent-To-Treat (m-ITT). The m-ITT population included all patients who started the study (randomized), who received the study medication and had at least one post-baseline mean highest-average-pain score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AGN 203818 60 mg | Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4 | 60.9 Percentage of Patients |
| AGN 203818 20 mg | Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4 | 58.0 Percentage of Patients |
| AGN 203818 3 mg | Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4 | 61.2 Percentage of Patients |
| Placebo | Percentage of Patients Who Experienced Adequate Relief of Irritable Bowel Syndrome (IBS) Pain (AR-IBS) at Week 4 | 67.3 Percentage of Patients |
Secondary
Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4
Percentage of patients who rated their condition as improved on the SGIC at week 4. The SGIC score was assessed using a 7-point scale (score of 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). Patients self-evaluated their overall change in symptoms (relief from symptoms of abdominal discomfort, pain, and altered bowel habits). An improved condition was defined as a score of 1, 2, or 3.
Time frame: Week 4
Population: Modified Intent-To-Treat (m-ITT). The m-ITT population included all patients who started the study (randomized), who received the study medication and had at least one post-baseline mean highest-average-pain score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AGN 203818 60 mg | Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4 | 76.1 Percentage of Patients |
| AGN 203818 20 mg | Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4 | 73.5 Percentage of Patients |
| AGN 203818 3 mg | Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4 | 85.7 Percentage of Patients |
| Placebo | Percentage of Patients Who Rated Their Condition as Improved on the Subject Global Impression of Change (SGIC) at Week 4 | 77.5 Percentage of Patients |