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

NCT ID: NCT04927221

Last Updated: 2022-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2021-12-21

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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

DC371739 20mg Dose MAD

Orally administered DC371739 tablets QD afer meal

Group Type: EXPERIMENTAL

DC371739 Tablets

Intervention Type: DRUG

Participants received one of 5 dose levels of DC371739 administered as single oral doses.

DC371739 Placebo MAD

Placebo orally administered

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo orally administered as comparison

Interventions

DC371739 Tablets

Participants received one of 5 dose levels of DC371739 administered as single oral doses.

Intervention Type: DRUG

Placebo

Placebo orally administered as comparison

Intervention Type: DRUG

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Hospital of Jilin University

OTHER

Sponsor Role: collaborator

Guangzhou JOYO Pharma Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Hospital of Jilin University

Changchun, Jilin, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35427476 (View on PubMed)

Other Identifiers

JYD0102

Identifier Type: -

Identifier Source: org_study_id