A Safety and Efficacy Study of DRL-17822, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Patients With Abnormal Cholesterol Levels

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate Efficacy, Safety and Tolerability of DRL-17822 in Patients With Type II Hyperlipidemia

The purpose of this study is to determine if a new drug, DRL-17822, is safe and effective in elevating high density lipoprotein cholesterol (HDL-C) and reducing low density lipoprotein cholesterol (LDL-C) in people with abnormal cholesterol levels that may put them at risk for heart disease.

Study Overview

• Status: Completed
• Conditions: Type II Hyperlipidemia
• Intervention / Treatment: Drug: DRL-17822 or placebo

Detailed Description

Cardiovascular disease is a leading cause of death worldwide. Among cardiovascular disorders, coronary heart disease (CHD) caused by atherosclerosis is the most common cause of morbidity and mortality. Prevention, stabilization and regression of atherosclerotic plaques may have a major impact on reducing the risk of acute coronary events.

LDL-C lowering agents, primarily the statins, are the current mainstay in the pharmacologic management of dyslipidemia. However even with stain use, residual CHD risk from dyslipidemia remains. Epidemiologic and observational studies have shown that HDL-C is also a strong independent predictor of CHD, suggesting that raising HDL-C levels might afford clinical benefit in the reduction of cardiovascular risk.

Presently only niacin is approved by the FDA for HDL-C elevation and can raise HDL-C levels by 20-30%. However its use can be limited by a high incidence of flushing and, less commonly, by elevation of blood glucose and potential hepatic toxicity.

Cholesteryl ester transfer protein (CETP) inhibitors are being explored for their ability to elevate HDL-C. A small molecule CETP inhibitor, torcetrapib, has been demonstrated to elevate HDL-C by 60-100%. However, a large clinical trial (ILLUMINATE) where it increased HDL-C by a mean of 72% compared to baseline was halted as it failed to show benefit. Post-hoc analysis of this study implicated an off-target increase in blood pressure as potentially counteracting any anti-atherosclerotic benefits. Post-hoc subgroup analysis showed that patients in the highest HDL-C quartile had a 57% reduction in the risk of cardiovascular events.

Increased blood pressure appears to be specifically related to torcetrapib as two other small molecule CETP inhibitors, anacetrapib and dalcetrapib, have not shown this in clinical trials and have been well tolerated. DRL-17822 has also not shown elevation of blood pressure in either animals or in normal volunteers.

This study will investigate the efficacy and tolerability of DRL-17822 as dyslipidemia monotherapy in patients with Type II hyperlipidemia.

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Genova, Italy
  • Milano, Italy
  • Modena, Italy
  • Palermo, Italy
  • Perugia, Italy
• Poland
  • Gdynia, Poland
  • Gniewkowo, Poland
  • Katowice, Poland
  • Wroclaw, Poland
• Ukraine
  • Chernivtsi, Ukraine
  • Kharkov, Ukraine
  • Kyiv, Ukraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Type II hyperlipidemia having lipid values of HDL-C: males ≤ 44 mg/dL (≤1.13 mmol/L), females ≤ 54 mg/dL (≤1.39 mmol/L); LDL-C: ≥ 130 mg/dL (≥3.33 mmol/L);
• Male or female, 18 to 70 years of age, inclusive. Female patients must be postmenopausal or surgically sterile. Men, unless surgically sterile must practice birth control from screening until the end of the study;
• Ability and willingness to give written informed consent;
• No clinically significant abnormal findings on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory profiles of both blood and urine.

Exclusion Criteria:

• Patients with significant cardiac disease such as myocardial infarction, heart failure, coronary or peripheral artery angioplasty, bypass graft surgery, severe or unstable angina pectoris, cardiac arrhythmias, hypertension or any other disease which requires treatment;
• Uncontrolled diabetes (HbA1c > 8.0%);
• History of symptomatic cerebrovascular disease such as symptomatic carotid artery disease, cerebrovascular hemorrhage, transient ischemic attack or carotid endarterectomy or any disease which requires treatment;
• History of clinically significant hematologic, renal, hepatic, neurologic, endocrine, oncologic, pulmonary, immunologic or psychiatric disorders;
• Any current or recent (within 4 weeks of run-in) concomitant therapy (apart from paracetamol/acetaminophen and non-steroidal anti-inflammatory drugs [NSAIDs]). Patients on previous concomitant treatment may enter the study if the treatment has been discontinued, when appropriate and if ethically justified, at least four weeks prior to run-in;
• Body mass index (BMI)> 35 kg/m(2);
• Positive for hepatitis B, C or HIV or known history or concurrent tuberculosis;
• Positive drug screen result (i.e., cocaine, opiates, amphetamine, cannabis, barbiturates, benzodiazepines and/or metadone);
• Pregnant, breast feeding or women of child-bearing potential;
• Regular use of non-drug therapies such as garlic supplements and St. John's Wort;
• Presence or history of alcoholism or drug abuse;
• Use of more than 21 units of alcohol per week for males or more than 14 units per week for females;
• Smoking within 3 months prior to screening;
• Relevant drug hypersensitivity or allergy or any serious adverse event reaction to lipid regulating agents;
• Administration of study drug in another drug study within 90 days prior to enrollment or participation in another drug trial from screening to last follow-up of this study; Any surgical or medical condition which makes the patient unsuitable to participate in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo capsule	Drug: DRL-17822 or placebo; DRL-17822 50, 150 or 300 mg or matching placebo once daily after breakfast
Experimental: DRL-17822 50 mg	Drug: DRL-17822 or placebo; DRL-17822 50, 150 or 300 mg or matching placebo once daily after breakfast
Experimental: DRL-17822 150 mg	Drug: DRL-17822 or placebo; DRL-17822 50, 150 or 300 mg or matching placebo once daily after breakfast
Experimental: DRL-17822 300 mg	Drug: DRL-17822 or placebo; DRL-17822 50, 150 or 300 mg or matching placebo once daily after breakfast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in HDL-C From Baseline	Percent change from baseline in HDL-C after 28 days of treatment in patients with Type II hyperlipidemia	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of DRL-17822	Incidence of treatment-related adverse events	28 days
Changes in Vital Signs Including Blood Pressure	Vital sign abnormalities reported as treatment-emergent AEs	28 days
To Evaluate Trough Levels of DRL-17822 in Plasma	Trough levels of DRL-17822 in plasma after 28 days of treatment	28 days
Changes in CETP Inhibition in Plasma	Percent change from baseline in CETP Inhibition	28 days
Changes in Other Lipids and Apolipoproteins	Change from baseline (LOCF, ITT population)	28 days

Collaborators and Investigators

• Sponsor: Dr. Reddy's Laboratories Limited
• Collaborators: PharmaNet
• Investigators: Study Director: Kent Allenby, MD, Dr. Reddy's Laboratories

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 6, 2011
• First Posted (Estimate): July 7, 2011

Study Record Updates

• Last Update Posted (Estimate): April 22, 2014
• Last Update Submitted That Met QC Criteria: March 18, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Double-Blind; Randomized; Placebo Controlled; CETP Inhibitor; Parallel Arm; Type II Hyperlipidemia; Cholesteryl Ester Transferase Protein Inhibitor
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipidemias; Hyperlipoproteinemia Type II; Hyperlipoproteinemias
• Other Study ID Numbers: DRL-17822/CD/004