Phase 1/2a Trial of YH12852 in Healthy Subjects and Patients With Functional Constipation

A Randomized, Double-blind/Open-label, Placebo/Active-controlled, Single/Multiple Dose, Parallel, Phase 1/2a Trial to Evaluate the Safety, Tolerability, PK , PD of YH12852 in Healthy Subjects and Patients With Functional Constipation

A randomized, double-blind/open-label, placebo/active-controlled, single/multiple dose, parallel, phase 1/2a trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of YH12852 in healthy subjects and patients with functional constipation

Study Overview

• Status: Completed
• Conditions: Functional Constipation
• Intervention / Treatment: Drug: Placebo; Drug: YH12852 IR 0.05mg; Drug: YH12852 IR 0.1mg; Drug: YH12852 IR 0.3mg; Drug: YH12852 IR 0.5mg; Drug: YH12852 IR 1mg; Drug: YH12852 IR 2mg; Drug: YH12852 IR 3mg; Drug: YH12852 DR1 0.5mg; Drug: YH12852 DR1 1mg; Drug: YH12852 DR1 2mg; Drug: YH12852 DR1 4mg; Drug: YH12852 DR2 8mg; Drug: Prucalopride 2mg

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be willing and able to provide written informed consent.
2. BMI within the range 18 to 25 kg/m2.

Exclusion Criteria:

1. History of positive serologic evidence for infectious disease including HBsAg, anti-HCV, anti-HIV.
2. Clinically significant lab/ECG abnormalities in the opinion of the investigator.

3. WOCBP who are unwilling or unable to use an adequate contraceptive method to avoid pregnancy for the entire study. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, bilateral tubectomy, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as amenorrhea for ≥ 12 consecutive months without another cause.

   Clinically acceptable contraceptive methods for this study: intrauterine devices (e.g., loop), physical barrier method (e.g., diaphragm, uterine cap, condom) with chemical barrier method (e.g., spermicide), sterile partner, practicing abstinence.

4. WOCBP who are willing to use hormonal methods or hormone-releasing device(e.g., mirena, implanon) for the entire study.
5. WOCBP who are pregnant or breastfeeding.
6. WOCBP with a positive pregnancy test prior to randomization.
7. Males who have not received a vasectomy must agree to use contraceptive methods defined in (a) and refrain from donating sperm throughout the study.
8. Presence of uncontrolled or severe medical illness.
9. Presence of a disease that require surgery at any time during the study.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YH12852 IR 0.05mg; Once daily	Drug: YH12852 IR 0.05mg
Experimental: YH12852 IR 0.1mg; Once daily	Drug: YH12852 IR 0.1mg
Experimental: YH12852 IR 0.3mg; Once daily	Drug: YH12852 IR 0.3mg
Experimental: YH12852 IR 0.5mg; Once daily	Drug: YH12852 IR 0.5mg
Experimental: YH12852 IR 1mg; Once daily	Drug: YH12852 IR 1mg
Experimental: YH12852 IR 2mg; Once daily	Drug: YH12852 IR 2mg
Experimental: YH12852 IR 3mg; Once daily	Drug: YH12852 IR 3mg
Experimental: YH12852 DR1 0.5mg; Once daily	Drug: YH12852 DR1 0.5mg
Experimental: YH12852 DR1 1mg; Once daily	Drug: YH12852 DR1 1mg
Experimental: YH12852 DR1 2mg; Once daily	Drug: YH12852 DR1 2mg
Experimental: YH12852 DR1 4mg; Once daily	Drug: YH12852 DR1 4mg
Experimental: YH12852 DR2 8mg; Once daily	Drug: YH12852 DR2 8mg
Active Comparator: Prucalopride 2mg; Once daily	Drug: Prucalopride 2mg
Placebo Comparator: Placebo; Once daily	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (IR/DR multiple dose cohort and Multiple low-dose IR cohort)		Day 1 pre-dose (0 hr) ~ 24 hrs post-dose
AUC0-24 (IR/DR multiple dose cohort and Multiple low-dose IR cohort)		Day 1 pre-dose (0 hr) ~ 24 hrs post-dose
Tmax(IR/DR multiple dose cohort and Multiple low-dose IR cohort)		Day 1 pre-dose (0 hr) ~ 24 hrs post-dose
C(IR multiple dose cohort)	CD5, CD10, CD12, CD13	Day 5, 10, 12 and 13
Cmax,ss(IR/DR multiple dose cohort and Multiple low-dose IR cohort)		Day 14
Cmax,ss (DR single dose cohort)		Day 1: pre-dose (0 hr) ~ 62hr and 86 hrs post-dose
AUClast (DR single dose cohort)		Day 1: pre-dose (0 hr) ~ 62hr and 86 hrs post-dose
C(DR multiple dose cohort and Multiple low-dose IR cohort)	CD5, CD13, CD14	Day 5, 13 and 14

Collaborators and Investigators

• Sponsor: Yuhan Corporation
• Investigators: Principal Investigator: Howard Lee, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital and College of Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: August 21, 2015
• First Submitted That Met QC Criteria: August 30, 2015
• First Posted (Estimate): September 2, 2015

Study Record Updates

• Last Update Posted (Estimate): October 31, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride; YH12852
• Other Study ID Numbers: YH12852-102