Phase I Study of D-0120 to Evaluate Safety and PK/PD Study in Healthy Volunteers

Study Overview
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Brief Summary
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This phase 1 study is a randomized, double-blind, placebo controlled, multiple-dose, dose-escalating study to evaluate the safety, tolerability, PK and PD of D-0120 in healthy volunteers.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, and Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of D-0120 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: D-0120
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be medically documented as healthy at physical examination Moderate smokers or non-smokers Subjects must be between the ages of 18 and 60 Subject must have a BMI between 18.0 and 30.0 kg/m2 (inclusive) Subjects must have a body weight of 50kg or higher for males and 45kg or higher for females Females must be non-pregnant and non-lactating, and either surgically sterile at least 6 months prior to the first study drug administration or post-menopausal for 12 months or greater Male subjects who are not vasectomized for at least 6 months, and who are sexually active with non-sterile female partner must be willing to use an acceptable contraceptive method throughout the study and for 90 days after the last study drug administration Male subjects with a pregnant partner must agree to use a condom from the first dosing until at least 90 days after the last study administration Subjects must have a complete blood count and platelet count within the normal range Subjects must have a normal urinalysis Subjects must have a normal estimated glomerular filtration rate Subjects must have a normal ECG Subjects must be able to understand the study procedures, risks involved and be able to comply with the study and follow-up procedures Male subjects must be willing not to donate sperm until 90 days following the last study drug administration Exclusion Criteria: Subjects with any history or clinical manifestations of disorders Subjects who have any history or suspicion of kidney stones Subjects who are HIV, Hep B or Hep C positive History of significant allergic reactions to any drug Clinically significant ECG abnormalities History of significant drug abuse within 1 year prior to screening or use of soft drugs within 3 months prior to screening or hard drugs within 1 year prior to screening Subjects who have used prescription dugs, over the counter drugs or herbal remedies within 14 days before day 1 Positive urine drug screen, alcohol breath at screening Subjects had undergone major surgery within 3 months Women who are pregnant or breastfeeding History of significant alcohol abuse Subjects who consumed Seville oranges-or grapefruit-containing food or beverages within 7 days before Day 1 and during the entire study duration. Subjects with any condition that, in the judgement of the investigator, would place him/her at undue risk Participation in a clinical research study involving the administration of an investigation or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to first dose Donation of plasma within 7 days prior to dosing

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: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: D-0120 Dose Ascending Cohorts 1-4<br>D-0120 dose daily for up to 7 days. | Drug: D-0120<br>* Randomized, Double-Blind, Placebo-Controlled, Multiple Dose and Dose Escalation of D-0120 or Placebo<br>|
| Placebo Comparator: Placebo Dose Ascending Cohorts 1-4<br>Placebo dose daily for up to 7 days | Drug: Placebo oral tablet<br>* Randomized, Double-Blind, Placebo-Controlled, Multiple Dose and Dose Escalation of D-0120 or Placebo<br>|
| Experimental: D-0120/Uric Acid Lowering Agent Cohort 6<br>D-0120 in combination with a uric acid lowering agent for up to 7 days of combination therapy | Drug: D-0120<br>* Randomized, Double-Blind, Placebo-Controlled, Multiple Dose and Dose Escalation of D-0120 or Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects with treatment related adverse events as assessed | Data will include clinical observations, ECG, clinical chemistry/hematology/urinalysis and vital signs | Reporting of adverse events starts at enrollment through the end of the follow up period (14 days (cohorts 1-4) and 16 days (cohort 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to observed Cmax (Tmax)for D-0120 | Blood samples will be collected to assess plasma concentrations of D-0120 at a series of timepoints to derive Tmax | Timeframe: Day 1-Day7 | 
| Area under the plasma concentration-time curve (AUC) for D-0120 | Blood samples will be collected to assess plasma concentration of D-0120 at a series of timepoints to derive AUC | Day 1-Day 7 | 
| Maximum Observed Plasma Concentration (Cmax) of D-0120 | Blood samples will be collect to assess plasma concentrations of D-0120 at a series of timepoints to derive Cmax | Day 1-Day 7 |