A Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week, Dose-Range-Finding Trial of YKP10811 Capsules Administered Once Daily to Subjects With Chronic Idiopathic Constipation

Study Overview
=================
Brief Summary
-----------------
This will be a multi-center, randomized, double-blind, placebo-controlled study of YKP10811 capsules in patients with chronic idiopathic constipation. Following a 2-week baseline period, approximately 320 eligible patients with <3 complete spontaneous bowel movements (CSBM) and ≤ 5 SBMs per week will be randomly assigned equally to receive one of the following oral treatments; placebo or YKP10811 capsules once daily for 12 weeks followed by a 2 week follow-up period. The objectives of this study are: To assess the efficacy of YKP10811 once daily at relieving constipation and associated symptoms in subjects with chronic idiopathic constipation. To determine the safety and tolerability of YKP10811 once daily in subjects with chronic idiopathic constipation.

Conditions
-----------------
Chronic Idiopathic Constipation

Intervention / Treatment
-----------------
* Drug: YKP10811
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who meet modified Rome II criteria for Chronic Constipation. Patients who are male or female, 18 to 65 years of age inclusive. At Visit 3, patients must have < 3 CSBMs per week and ≤ 5 SBMs per week during the 2-week baseline period. Exclusion Criteria: Patients who meet Rome II criteria for Irritable Bowel Syndrome (IBS-C). Patients with constipation that is drug-induced, or secondary to endocrine, metabolic or, surgery. Patients with a clinically significant diseases that would limit the patient's ability to complete and/or participate in the study, including gastrointestinal disorder or surgery, an endocrine abnormality (e.g., diabetes), impaired renal function (GFR of < 55mL/minute/1.73m2), uncontrolled pulmonary diseases (including asthma), uncontrolled cardiovascular disease (a history of myocardial infarction or cerebrovascular accident within 6 months prior to screening) or significant neurological diseases. Patients with a history of inflammatory bowel disease. Patients with a history of cancer (other than basal cell or squamous cell carcinoma of the skin completely excised) unless the malignancy has been in complete remission for at least 5 years prior to screening. Patients who started a special diet and/or an intense physical workout program within 30 days prior to the beginning of the baseline period or who are intending to substantially modify their dietary habits at any time during the study (patients on a stable, continuous regimen of fiber therapy for at least 30 days prior to the pretreatment baseline period are allowed to continue that therapy, provided that they continue at a constant dose throughout the study. Patients with a history of clinically significant hypersensitivity or allergy (facial swelling, hives, breathing difficulty, Stevens-Johnson syndrome etc), in response to any medication, either prescription or nonprescription including an investigational drug, dietary supplement, or herbal medicine.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator<br>Placebo Comparator | Drug: Placebo<br> <br> |
| Experimental: YKP10811 High Dose<br>YKP10811 High Dose | Drug: YKP10811<br> <br> |
| Experimental: YKP10811 Mid Dose<br>YKP10811 Mid Dose | Drug: YKP10811<br> <br> |
| Experimental: YKP10811 Low Dose<br>YKP10811 Low Dose | Drug: YKP10811<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with improved bowel movement frequency |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool frequency |  | 12 weeks | 
| Daily average ratings of stool consistency |  | 12 weeks | 
| Instances of rescue medicine usage |  | 12 weeks | 
| Onset time to CSBM |  | 12 weeks | 
| Onset time to SBM |  | 12 weeks | 
| Severity of straining |  | 12 weeks | 
| Abdominal discomfort |  | 12 weeks | 
| Abdominal pain |  | 12 weeks | 
| Bloating |  | 12 weeks | 
| Constipation severity |  | 12 weeks |