Clinical trial NCT01388816: A Safety and Efficacy Study of DRL-17822, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Patients With Abnormal Cholesterol Levels
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate Efficacy, Safety and Tolerability of DRL-17822 in Patients With Type II Hyperlipidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type II Hyperlipidemia
Keywords: Randomized
Double-Blind
Placebo Controlled
Parallel Arm
Type II Hyperlipidemia
Cholesteryl Ester Transferase Protein Inhibitor
CETP Inhibitor
Lead sponsor: Dr. Reddy's Laboratories Limited
Sponsor class: INDUSTRY
Collaborators: name: PharmaNet
First posted: 2011-07-07
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change in HDL-C From Baseline
timeFrame: 28 days
Secondary outcomes:
measure: Safety and Tolerability of DRL-17822
timeFrame: 28 days
measure: Changes in Vital Signs Including Blood Pressure
timeFrame: 28 days
measure: To Evaluate Trough Levels of DRL-17822 in Plasma
timeFrame: 28 days
measure: Changes in CETP Inhibition in Plasma
timeFrame: 28 days
measure: Changes in Other Lipids and Apolipoproteins
timeFrame: 28 days
Other outcomes:
Locations:
city: Genova
country: Italy
city: Milano
country: Italy
city: Modena
country: Italy
city: Palermo
country: Italy
city: Perugia
country: Italy
city: Gdynia
country: Poland
city: Gniewkowo
country: Poland
city: Katowice
country: Poland
city: Wroclaw
country: Poland
city: Chernivtsi
country: Ukraine
city: Kharkov
country: Ukraine
city: Kyiv
country: Ukraine
Study officials:
affiliation: Dr. Reddy's Laboratories
name: Kent Allenby, MD
role: STUDY_DIRECTOR
References: