Safety and Efficacy of Oral AGN 203818 for the Relief of Irritable Bowel Syndrome Pain

Study Overview
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Brief Summary
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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.

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: AGN 203818
* Drug: AGN 203818
* Drug: AGN 203818
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Irritable Bowel Syndrome Moderate or severe IBS pain Exclusion Criteria: Any other uncontrolled disease Pregnant or nursing females

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGN 203818 3 mg<br>Part A: AGN 203818 3mg capsule every 12 hours for 4 weeks | Drug: AGN 203818<br>* Part A: 3 mg AGN203818 capsule every 12 hours for 4 weeks<br>|
| Experimental: AGN 203818 20 mg<br>Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks | Drug: AGN 203818<br>* Part A: 20 mg AGN203818 capsule every 12 hours for 4 weeks<br>|
| Experimental: AGN 203818 60 mg<br>Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks | Drug: AGN 203818<br>* Part A: 60 mg AGN203818 capsule every 12 hours for 4 weeks<br>|
| Placebo Comparator: Placebo<br>Part A: Placebo capsule every 12 hours for 4 weeks | Drug: placebo<br>* Part A: placebo capsule every 12 hours for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 4 | 
| 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. | Week 4 | 
| 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. | Baseline, Week 4 |