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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Constipation; Functional Constipation
• Intervention / Treatment: Drug: Placebo Capsule; Drug: YKP10811 Drug Product Capsule; Drug: YKP10811 Drug Product Capsule; Drug: YKP10811 Drug Product Capsule

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Body Mass Index of 19 through 40 kg/m2
3. Participants must be willing to follow dietary restrictions
4. Females of childbearing potential (ie, not menopausal, no hysterectomy, no bilateral oophorectomy) must complete a negative pregnancy test (urine) prior to receiving any radioisotopes
5. No evidence of pelvic floor dysfunction
6. If clinically indicated, absence of an evacuation disorder should be confirmed within 30 days prior to the first dose of study medication
7. At Screening, patients must meet ROME III Criteria for FC, which assumes an absence of a structural or biochemical explanation
8. The patient's screening (baseline) colonic transit test must show a GC ≤ 2.4 at 24 hours; and
9. Baseline EKG shows QTc interval ≤ 450mSec

Exclusion Criteria:

1. History of clinically-significant manifestations or current abnormality of any organ system
2. History of inflammatory bowel disease
3. Any history of GI surgery within 6 months prior to the first dose of study medication
4. History of clinically-significant prolonged diarrhea, in the absence of a laxative
5. 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
6. Any clinically-significant surgical procedure within 30 days prior to the first dose of study medication
7. History of alcoholism or drug addiction within 12 months prior to the first dose of study medication
8. 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
9. Patients who are breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: SK Life Science, Inc.

Publications and helpful links

General Publications

• Shin A, Acosta A, Camilleri M, Boldingh A, Burton D, Ryks M, Rhoten D, Zinsmeister AR. A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol. 2015 Apr;13(4):701-8.e1. doi: 10.1016/j.cgh.2014.08.012. Epub 2014 Aug 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: January 27, 2012
• First Submitted That Met QC Criteria: January 31, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Estimate): July 4, 2014
• Last Update Submitted That Met QC Criteria: July 2, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Gastric Emptying; gastrointestinal transit; colonic transit; Functional Constipation (FC); Chronic constipation (CC); Colon Transit; multiple doses of YKP10811
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: YKP10811C003