Multiple Ascending Dose Study to Evaluate the Safety, Tolerability of DC371739 Treatment in Hypercholesterolemic

Study Overview
=================
Brief Summary
-----------------
This study is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of DC739 after multiple-dose oral administration, to explore the clinical effective dose, and to initially explore the efficacy and safety in hypercholesterolemia subjects.

Detailed Description
-----------------
Totally about 30-50 qualified subjects were assigned to one of the following dose groups：20mg, 40mg, 60mg, 80mg, 120 mg (60mg and 120mg is the optional dose group). Each of the dose groups will include 10 subjects (8 for DC739 and 2 for placebo). Subjects will be admitted for treatment on day -1 and receive the first dose of study drug or placebo on day 1 and then treat for 28 days. Subjects from different dose groups were enrolled in turn, the next dose group is conducted on the premise that the D15 safety evaluation was completed after the administration of the previous dose group with the result was tolerance. Blood samples will be collected on day 1 for 48 hours and day 28 for 72 hours after administration for pharmacokinetic data analysis. Blood lipid will be collected for effectiveness evaluation. PCSK9 and ANGPTL3, Urine and feces were collected for explore analysis.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Phase Ib/IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DC739 Multiple-Dose in Hypercholesterolemic Subjects.

Conditions
-----------------
Hypercholesterolemia

Intervention / Treatment
-----------------
* Drug: DC371739 Tablets
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged 18 to 65 years (inclusive 18 and 65); Body mass index of 18 to 32 kg/m2(inclusive); Hypercholesterolemia subjects with LDL-C≥2.6mmol/L(100mg/dL); Male or female subjects who had no immediate plans to have children, the serum pregnancy test of women was negative at the time of screening, and agreed to use strict contraceptive measures throughout the study period and up to 6 months after the last dose; Exclusion Criteria: ECG confirmed that the QT interval was prolonged > 450ms (QT interval corrected for heart rate by Bazetts formula [QTCB]); Use of statins (lovastatin, simvastatin, pravastatin, mevastatin, fluvastatin, atorvastatin, cerivastatin, rosuvastatin, pitavastatin, etc.) , ezetimibe, Xuezhikan, and other lipid-lowering treatment within 2 months prior to screening; use of PCSK9 monoclonal antibodies , fibric acid drugs (such as fenofibrate, gemfibrozil) and probucol within 3 months prior to screening; Use of warfarin, systemic steroids, cyclosporine, or other immunosuppressive therapy within months prior to screening; Subjects with HIV-AB , HBsAg, ANTI-TP , HCV-AB positive; A history of prescription drug abuse and illicit drug abuse within 6 months prior to screening; A history of alcohol abuse within 6 months prior to screening;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to one of 5 groups in parallel for the duration of the study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DC371739 20mg Dose MAD<br>Orally administered DC371739 tablets QD afer meal | Drug: DC371739 Tablets<br>* Participants received one of 5 dose levels of DC371739 administered as single oral doses.<br>|
| Placebo Comparator: DC371739 Placebo MAD<br>Placebo orally administered | Drug: Placebo<br>* Placebo orally administered as comparison<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tolerability evaluation | 12-lead ECG | From informed consent until Day 42. | 
| Safety evaluation | adverse events (AE/SAEs) | From informed consent until Day 42. | 
| Pharmacodynamic evaluation | Cmax | From informed consent until Day 31. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective evaluation | LDL-C | From informed consent until Day 29. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypercholesterolemia, Pharmacokinetics, Pharmacodynamics