D-0120 Safety and PK/PD, Food Effect Study in Healthy Volunteers

Study Overview
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Brief Summary
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This initial clinical study in the US will be a randomized, double-blind, placebo-controlled, single-dose, dose-escalation, and sequential cohort study to evaluate the safety, tolerability, PK and PD of D-0120-NA in fasting, healthy volunteers (HVs). In food effect cohort, subjects will each receive 2 doses of D-0120-NA in an open-label manner; once in the fasted state and once in the fed state.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Dose, and Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics; Including an Open-label Cohort to Determine the Effect of Food on the Pharmacokinetics of D-0120-NA Tablet in Healthy Volunteers in the United States

Conditions
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Gout

Intervention / Treatment
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* Drug: D-0120


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be medically documented as healthy and acceptable at physical examination. Subjects serum uric acid level at screening ≥ 4.5 mg/dL. Subjects must have a BMI between 18.0 and 30.0 kg/m2 and a body weight of 50 kg or higher Subjects must have all laboratory parameters within the normal range or considered not clinically significant by the principal investigator. Subjects must have a normal urinalysis, eGFR, ECG or results considered not clinically significant by the principal investigator. Subjects are able to understand the study procedures and risks involved and must provide signed informed consent to participate in the study. Exclusion Criteria: Any history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders. Any history or suspicion of kidney stones. Positive for HIV, Hepatitis B, and/or Hepatitis C. Subjects who have used prescription drugs, over-the-counter drugs, or herbal remedies within 14 days before Day 1 of study medication dosing. Undergone major surgery within 3 months prior to Day 1. Women who are pregnant or breastfeeding. Subjects who received any investigational test article within 5 half-lives or 30 days prior to Day 1 study medication dosing. Subjects who consumed Seville oranges- or grapefruit-containing foods or beverages within 7 days before Day 1 and during the entire study duration. Subjects with any condition that, in the judgment of the investigator, would place him/her at undue risk, or potentially compromise the results or interpretation of the study.

Ages Eligible for Study
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Minimum Age: 18 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-0120 Dose 1<br>D-0120 Dose 1 Patients will get D-0120 single agent or placebo of matching size during dose escalation | Drug: D-0120<br>* oral, single dose<br>|
| Experimental: D-0120 Dose 2<br>D-0120 Dose 2 Patients will get D-0120 single agent or placebo of matching size during dose escalation | Drug: D-0120<br>* oral, single dose<br>|
| Experimental: D-0120 Dose 3<br>D-0120 Dose 3 Patients will get D-0120 single agent or placebo of matching size during dose escalation | Drug: D-0120<br>* oral, single dose<br>|
| Experimental: D-0120 Dose 4<br>D-0120 Dose 4 Patients will get D-0120 single agent or placebo of matching size during dose escalation | Drug: D-0120<br>* oral, single dose<br>|
| Experimental: D-0120 Dose 5<br>D-0120 Dose 5 Patients will get D-0120 single agent once in the fasted state and once in the fed state. | Drug: D-0120<br>* oral, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Adverse Events and changes of Laboratory, Electrocardiogram, and Vital Signs | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic: area under the plasma concentration versus time curve (AUC) | AUC: area under the plasma concentration versus time curve for D-0120 | Day-1 through 3 | 
| Pharmacokinetic: maximum plasma drug concentration (Cmax) | Cmax: maximum plasma drug concentration of D-0120 | Day-1 through 3 | 
| Pharmacokinetic: Time to reach the Cmax (Tmax) | Tmax: Time to reach the Cmax of D-0120 | Day-1 through 3 | 
| Pharmacokinetic: Apparent terminal half-life (t1/2) | t1/2: apparent terminal half-life of D-0120 | Day-1 through 3 | 
| Pharmacokinetic: Apparent oral clearance (CL/F) | CL/F: Apparent oral clearance of D-0120 | Day-1 through 3 | 
| Pharmacokinetic: Apparent volume of distribution (Vz/F) | Vz/F: Apparent volume of distribution of D-0120 | Day-1 through 3 | 
| PD profile of D-0120 from plasma and urine | Profile in terms of Serum uric acid and creatinine; Urine uric acid and creatinine. These parameters will be combined to report fractional excretion of uric acid (FEUa %) | Day-1 through 3 |