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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Functional Constipation

Intervention / Treatment
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* 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
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be willing and able to provide written informed consent. BMI within the range 18 to 25 kg/m2. Exclusion Criteria: History of positive serologic evidence for infectious disease including HBsAg, anti-HCV, anti-HIV. Clinically significant lab/ECG abnormalities in the opinion of the investigator. 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. WOCBP who are willing to use hormonal methods or hormone-releasing device(e.g., mirena, implanon) for the entire study. WOCBP who are pregnant or breastfeeding. WOCBP with a positive pregnancy test prior to randomization. Males who have not received a vasectomy must agree to use contraceptive methods defined in (a) and refrain from donating sperm throughout the study. Presence of uncontrolled or severe medical illness. Presence of a disease that require surgery at any time during the study.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |