To Assess the Safety, Efficacy and Tolerability of CKD-519, Administered With HMG-CoA Reductase Inhibitors

Multicenter, Parallel-group, Double-blind, Randomized, Active-controlled, Dose-ranging Study to Assess the Safety, Efficacy, and Tolerability of CKD-519, Administered With HMG-CoA Reductase Inhibitors, in Subjects With Dyslipidemia

A multicenter, double-blind, parallel-group, active-controlled, dose-ranging study to assess the safety and efficacy of the novel cholesteryl ester transfer protein (CETP) inhibitor CKD-519 in combination with atorvastatin or rosuvastatin in subjects with dyslipidemia.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias
• Intervention / Treatment: Drug: Atorvastatin 20mg; Drug: Atorvastatin 20 mg + CKD-519 50 mg; Drug: Atorvastatin 20 mg + CKD-519 100 mg; Drug: Atorvastatin 20 mg + CKD-519 200 mg; Drug: Rosuvastatin 10 mg; Drug: Rosuvastatin 10 mg + CKD-519 100 mg

Detailed Description

The purpose of this study is to assess the safety, efficacy, and tolerability of CKD-519, administered with HMG-CoA reductase inhibitors in subjects with dyslipidemia

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Not provided

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 80 years.

2. Dyslipidemia with LDL-C

   • At screening if untreated: 100 to 190 mg/dL
   • At screening if treated with statins or other lipid-lowering drugs: 100 to 170 mg/dL
   • At start of double-blind treatment: 100 to 190 mg/dL.
3. HDL-C <45 mg/dL (males) or <50 mg/dL (females).
4. Fasting TG <400 mg/dL.

5. Presence of the following conditions is permitted but not mandatory, at the discretion of the investigator:

   • Treated and stable coronary heart disease without acute events in the past 3 months and stable, state-of-the-art medication.
   • Treated and stable carotid artery disease or peripheral arterial disease on stable, standard medication for the past 3 months
   • Treated and stable Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤9.5%.
6. Willing and able to sign the informed consent form (ICF).

Exclusion Criteria:

1. Chronic heart failure as defined by New York Heart Association classes III and IV.
2. Uncontrolled cardiac arrhythmias.
3. Myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or unstable angina in past 3 months before Visit 1.
4. Stroke or transient ischemic attack within 3 months before Visit 1.
5. Uncontrolled hypertension.

6. Clinically significant laboratory abnormalities

   • Aspartate aminotransferase or alanine aminotransferase >2 times upper limit of normal range
   • Bilirubin >1.5 times upper limit of normal range
   • Creatine kinase >2 times upper limit of normal range.
7. Any active nephropathy or estimated glomerular filtration rate <60 mL/min/1.73m2 or on kidney dialysis.
8. Poorly controlled (thyroid-stimulating hormone [TSH] >2 times upper limit of normal) hyperthyroidism.
9. Homozygous familial hypercholesterolemia.
10. Intolerance or hypersensitivity to atorvastatin or rosuvastatin.
11. Prior treatment with any CETP inhibitor.
12. Positive for human immunodeficiency virus (HIV) positive, hepatitis B or hepatitis C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Atorvastatin 20 mg; To administrate Atorvastatin 20 mg and 4 Placebos, PO, QD for 4weeks	Drug: Atorvastatin 20mg; PO daily for 4weeks; Other Names: Lipitor 20mg
EXPERIMENTAL: Atorvastatin 20 mg + CKD-519 50 mg; To administrate Atorvastatin 20 mg, CKD-519 50 mg and 3 Placebos, PO, QD for 4weeks	Drug: Atorvastatin 20 mg + CKD-519 50 mg; PO daily for 4weeks; Other Names: Lipitor 20mg
EXPERIMENTAL: Atorvastatin 20 mg + CKD-519 100 mg; To administrate Atorvastatin 20 mg, CKD-519 100 mg and 3 Placebos, PO, QD for 4weeks	Drug: Atorvastatin 20 mg + CKD-519 100 mg; PO daily for 4weeks; Other Names: Lipitor 20mg
EXPERIMENTAL: Atorvastatin 20 mg + CKD-519 200 mg; To administrate Atorvastatin 20 mg, CKD-519 200 mg and 2 Placebos, PO, QD for 4weeks	Drug: Atorvastatin 20 mg + CKD-519 200 mg; PO daily for 4weeks; Other Names: Lipitor 20mg
ACTIVE_COMPARATOR: Rosuvastatin 10 mg; To administrate Rosuvastatin 10 mg and 4 Placebos, PO, QD for 4weeks	Drug: Rosuvastatin 10 mg; PO daily for 4weeks; Other Names: Crestor 10mg
EXPERIMENTAL: Rosuvastatin 10 mg + CKD-519 100 mg; To administrate Rosuvastatin 10 mg, CKD-519 100 mg and 3 Placebos, PO, QD for 4weeks	Drug: Rosuvastatin 10 mg + CKD-519 100 mg; PO daily for 4weeks; Other Names: Crestor 10mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change from baseline (Visit 3) in LDL-C	at Week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change from baseline in HDL-C	at Weeks 2 and Week 4
Percentage change from baseline in concentration of HDL particles (HDL-P)	at Weeks 2 and 4
Change from baseline in size of HDL particles (HDL-P)	at Weeks 2 and 4
Percentage change from baseline in LDL-C	at Week 2
Change in concentration from baseline in LDL-C	at Weeks 2 and 4
Change in concentration from baseline in HDL-C	at Weeks 2 and 4
Percentage change from baseline in total cholesterol, TG, and non-HDL-C	at Weeks 2 and 4
Change in concentration from baseline in total cholesterol, TG, and non-HDL-C	at Weeks 2 and 4
Percentage change from baseline in apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), and apolipoprotein E (Apo E)	at Weeks 2 and 4
Change in concentration from baseline in Apo B, Apo A1, and Apo E	at Weeks 2 and 4
Percentage change from baseline in lipoprotein(a) (Lp-a)	at Weeks 2 and 4
Change in concentration from baseline in Lp-a	at Weeks 2 and 4
Change in concentration from baseline in high-sensitivity C-reactive protein at	at Weeks 2 and 4

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Study Director: Kyung-Mi Park, PhD, Chong Kun Dang Pharm.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 23, 2017
• Primary Completion (ACTUAL): December 30, 2017
• Study Completion (ACTUAL): January 30, 2018

Study Registration Dates

• First Submitted: November 27, 2016
• First Submitted That Met QC Criteria: November 29, 2016
• First Posted (ESTIMATE): November 30, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 5, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Dyslipidemia; Hyperlipidemia; CETP Inhibitors
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: 148HL16011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No