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

• ClinicalTrials.gov Identifier: NCT04927221
• Recruitment Status: Completed
• First Posted: June 15, 2021
• Last Update Posted: March 16, 2022
• Sponsor: Guangzhou JOYO Pharma Co., Ltd
• Collaborator: The First Hospital of Jilin University
• Information provided by (Responsible Party): Guangzhou JOYO Pharma Co., Ltd

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: DC371739 Tablets; Drug: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants are assigned to one of 5 groups in parallel for the duration of the study
• Masking: Single (Participant)
• Masking Description: Participant, Investigator
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: April 1, 2021
• Actual Primary Completion Date: December 21, 2021
• Actual Study Completion Date: December 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: DC371739 20mg Dose MAD; Orally administered DC371739 tablets QD afer meal	Drug: DC371739 Tablets; Participants received one of 5 dose levels of DC371739 administered as single oral doses.
Placebo Comparator: DC371739 Placebo MAD; Placebo orally administered	Drug: Placebo; Placebo orally administered as comparison

Outcome Measures

Primary Outcome Measures :

1. tolerability evaluation [ Time Frame: From informed consent until Day 42. ]
   12-lead ECG
2. Safety evaluation [ Time Frame: From informed consent until Day 42. ]
   adverse events (AE/SAEs)
3. Pharmacodynamic evaluation [ Time Frame: From informed consent until Day 31. ]
   Cmax

Secondary Outcome Measures :

1. Effective evaluation [ Time Frame: From informed consent until Day 29. ]
   LDL-C

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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;

Contacts and Locations

Locations

China, Ji Lin

The First Hospital of Jilin University

Changchun, Ji Lin, China

Sponsors and Collaborators

Guangzhou JOYO Pharma Co., Ltd

The First Hospital of Jilin University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wang J, Zhao J, Yan C, Xi C, Wu C, Zhao J, Li F, Ding Y, Zhang R, Qi S, Li X, Liu C, Hou W, Chen H, Wang Y, Wu D, Chen K, Jiang H, Huang H, Liu H. Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial. Cell Metab. 2022 May 3;34(5):667-680.e6. doi: 10.1016/j.cmet.2022.03.006. Epub 2022 Apr 14.

• Responsible Party: Guangzhou JOYO Pharma Co., Ltd
• ClinicalTrials.gov Identifier: NCT04927221
• Other Study ID Numbers: JYD0102
• First Posted: June 15, 2021
• Last Update Posted: March 16, 2022
• Last Verified: May 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Guangzhou JOYO Pharma Co., Ltd:

Hypercholesterolemia; Pharmacokinetics; Pharmacodynamics

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases