A Phase 2 Study to Evaluate Pharmacodynamics of YKP10811 in Patients With Chronic or Functional Constipation

Study Overview
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Brief Summary
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This will be a single-center, randomized, parallel group, multiple dose administration, double-blind, placebo-controlled study to evaluate the effects of YKP10811 on gastric, small bowel, and colonic transit in patients with Chronic Constipation or Functional Constipation. Four groups including a placebo group will be enrolled and will receive multiple oral doses of YKP10811 or matching placebo.

Detailed Description
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If the participant fulfills the initial eligibility criteria, the patient will be randomized to 1 of the active treatment groups or placebo. During the treatment period, patients will receive study medication once daily for 8 days. Patients will undergo scintigraphic assessment of gastric, small bowel and colonic transit of solids over the 48-hour period. Patients will be males or females, 18 through 65 years of age with a body mass index (BMI) of 19 through 40 kg/m2, with Chronic Constipation or Functional Constipation and no evidence of evacuation disorder as assessed by the Investigator and meet all the inclusion criteria and none of the exclusion criteria.

Official Title
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A Phase II, Single-Center, Randomized, Parallel Group, Multiple Administration, Double-Blind, Placebo-Controlled Study to Evaluate the Pharmacodynamics of YKP10811 in Patients With Chronic or Functional Constipation

Conditions
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Chronic Constipation, Functional Constipation

Intervention / Treatment
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* Drug: Placebo Capsule
* Drug: YKP10811 Drug Product Capsule
* Drug: YKP10811 Drug Product Capsule
* Drug: YKP10811 Drug Product Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smokers (refrained from any tobacco or nicotine usage, including smokeless tobacco, nicotine patches, etc.) for at least 6 months prior to Day 1 of the study Body Mass Index of 19 through 40 kg/m2 Participants must be willing to follow dietary restrictions Females of childbearing potential (ie, not menopausal, no hysterectomy, no bilateral oophorectomy) must complete a negative pregnancy test (urine) prior to receiving any radioisotopes No evidence of pelvic floor dysfunction If clinically indicated, absence of an evacuation disorder should be confirmed within 30 days prior to the first dose of study medication At Screening, patients must meet ROME III Criteria for FC, which assumes an absence of a structural or biochemical explanation The patient's screening (baseline) colonic transit test must show a GC ≤ 2.4 at 24 hours; and Baseline EKG shows QTc interval ≤ 450mSec Exclusion Criteria: History of clinically-significant manifestations or current abnormality of any organ system History of inflammatory bowel disease Any history of GI surgery within 6 months prior to the first dose of study medication History of clinically-significant prolonged diarrhea, in the absence of a laxative Patients who have started a special dietary habit and/or an intense physical workout program within 4 weeks prior to the first dose of study medication Any clinically-significant surgical procedure within 30 days prior to the first dose of study medication History of alcoholism or drug addiction within 12 months prior to the first dose of study medication Any patient who has had an acute illness within 5 days prior to the first dose of study medication, eg, flu syndrome, GI virus, indigestion Patients who are breastfeeding

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

Sexes Eligible for Study
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All

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Capsule<br>Placebo Capsules | Drug: Placebo Capsule<br>* This is the placebo capsule<br>|
| Active Comparator: YKP10811 Drug Product Capsule, 10 mg<br> | Drug: YKP10811 Drug Product Capsule<br>* The drug product, YKP10811, 10 mg under investigation<br>|
| Active Comparator: YKP10811 Drug Product Capsule, 20 mg<br> | Drug: YKP10811 Drug Product Capsule<br>* The drug product, YKP10811, 20 mg under investigation<br>|
| Active Comparator: YKP10811 Drug Product Capsule, 30 mg<br> | Drug: YKP10811 Drug Product Capsule<br>* The drug product, YKP10811, 30 mg under investigation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colonic Geometric Center (GC) at 24 hours | The colonic GC at 24 hours is the measurement of the move of the food within the GI track. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying half time | The gastric emptying half time is the time to empty the half of the ingested solid food in the stomach. | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic constipation (CC), Functional Constipation (FC), Colon Transit, Gastric Emptying, multiple doses of YKP10811, gastrointestinal transit, colonic transit