A study comparing several dose levels of LY3015014 in patients with high cholesterol studying the safety and ability of LY3015014 to reduce cholesterol

• Conditions: Primary hypercholesterolaemia; MedDRA version: 14.1Level: PTClassification code 10020603Term: HypercholesterolaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2013-000622-55-CZ
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-03
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 528

Inclusion Criteria

[1] Men or women greater than or equal to 18 years of age and less than or equal to 65 years of age

[2] Diagnosed with primary hypercholesterolemia (HC) defined as LDL =100 mg/dL (2.6 mmol/L) and TG =450 mg/dL (5.1 mmol/L)
o A subset of patients (~ 20%) with an LDL-C =80 mg/dL to <100 mg/dL (=2.1 mmol/L to <2. 6 mmol/L) will also be allowed.
o Includes at least ~20% heterozygous familial hypercholesterolemia (HeFH) and polygenic (non-familial) HC patients.

[3] Are on a stable diet and stable daily dose of atorvastatin,
simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, or
pitavastatin for at least 6 weeks and further adjustments of statin dose
are not deemed clinically indicated by the investigator, or up to ~20% of
patients with history of statin intolerance (i.e. patients who cannot
tolerate any dose of at least 1 statin) who are not on statin treatment for
at least 6 weeks, with or without a stable dose of ezetimibe for at least 6
weeks.
[4] Male patients with partner of childbearing potential: agree to use barrier protection during sexual intercourse during the study and for 3 months following the administration of the last dose of investigational product.
[5] Female patients including:
• Women not of child bearing potential due to surgical sterilization
(hysterectomy or bilateral oophorectomy or tubal ligation) or
menopause. Women with an intact uterus are deemed postmenopausal if
they have a cessation of menses for at least 1 year (or 6 to 12 months of
spontaneous amenorrhea with follicle stimulating hormone >40 mIU/mL
(>40 IU/L); not taking hormones or oral contraceptives within 1 year.
• Women of child bearing potential who have a negative urine or serum
pregnancy test, are not breast feeding, and agree to use a reliable
method of birth control up to at least 3 months following the last dose of
study drug, where reliable is defined as birth control that results in a low
failure rate (i.e., <1% per year) when used consistently and correctly.
[6] Have given informed consent to participate in the study. Women of child bearing potential who have a negative urine or serum pregnancy test and agree to use a reliable method of birth control up to at least 3 months following the last dose of study drug, where reliable is defined as birth control that results in a low failure rate (i.e., <1% per year) when used consistently and correctly.
[6] Have given informed consent to participate in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 317
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 211

Exclusion Criteria

[1] Have secondary HC or homozygous familial HC.
[2] Have had myocardial infarction (MI), unstable angina (UA), percutaneous coronary intervention, coronary artery bypass graft, stroke, or deep vein thrombosis/pulmonary embolism within 3 months of screening, or have planned cardiovascular surgery or percutaneous coronary intervention.
[3] Have symptoms consistent with moderate or severe heart failure or are receiving treatment for symptomatic congestive heart failure (CHF) or known left ventricular ejection fraction (LVEF) <30%. >160 mmHg or diastolic blood pressure >100 mmHg.
[5] Have diabetes mellitus (type 1 or 2) that requires or is likely to
require any injectable glucose lowering therapy (including insulins)
during the course of the study or have hemoglobin A1c (HbA1c) =8.5%.
[6] Have thyroid-stimulating hormone (TSH) levels outside normal
reference range for the central laboratory. Patients who are clinically euthyroid and on stable thyroid replacement therapy for at least 2months prior to screening and who are anticipated to remain on this dose throughout the trial period are acceptable exceptions to this criterion.
[7] Have a history of adrenal insufficiency, Cushing's syndrome, or other adrenal gland disorder.
[8] Have a history of vitamin E deficiency or fat malabsorption
syndrome.
[9] Have a serum creatinine =176.8 µM/L, nephrotic syndrome, or end stage renal disease and use renal replacement therapy such as
hemodialysis or peritoneal dialysis
[10] Have active hepatobiliary disease, serologic evidence of past or active hepatitis B or C, or past or active gallbladder disease.
[11] Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), or total bilirubin >2X ULN.
[12] Have a history or presence of a chronic muscular or neuromuscular disease including prior rhabdomyolysis or drug-induced myopathy or an unexplained/documented elevation in creatine kinase (CK) >3X ULN.
[13]Have hemoglobin <10 g/dL (6.2 mmol/L) in women and <11 g/dL (6.83 mmol/L) in men.
[14] Have a history of allergy, hypersensitivity or intolerance to drug preparations containing LY3015014, other PCSK9 antibodies, other monoclonal antibodies or any components of the formulation.
[15] Have a history of human immunodeficiency virus infection (HIV) infection, positive human HIV antibodies or other immune deficiency disorder.
[16] Have planned or are likely to require major surgery requiring
anesthesia or hospitalization during the course of the study.
[17] Have chronic alcohol or drug abuse or dependency.
[18] Are currently under suspicion of having any cancer or malignancy or have had a history of cancer in the past 2 years, with the exception of non-melanoma skin cancers, cervical cancer in situ, breast ductal carcinoma in situ or stage 1 prostate cancer.
[19] Have an active serious infection.
[20] Have a history or presence of cardiovascular, respiratory,
endocrine, gastrointestinal, hematological, autoimmune, metabolic,
neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data.
[21] Have started or stopped taking a statin or ezetimibe medication, or changed statin dose regimen within 6 weeks of randomization.
[22] Are on a statin regimen other than daily dosing (for example, an every-other-day statin regime

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified