Primary hypercholesterolaemia MedDRA version: 14.1 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: LY3015014
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Not available
Current Sponsor code: LY3015014
Other descriptive name: LY3015014
Concentration
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
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 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., =65 years) yes F.1.3.1 Number of subjects for this age range 211
Exclusion criteria
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) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the mean percentage change from baseline to week 16 in low-density lipoprotein cholesterol (LDL-C) measured using beta quantification with LY3015014 compared with placebo, in patients with primary hypercholesterolemia, when added to statin and diet (or diet alone in statin-intolerant patients) with or without ezetimibe.;Secondary Objective: • To assess the absolute change in LDL-C measured using beta quantification from baseline to week 16 with LY3015014 compared with placebo • To assess the dose-response, exposure-response and time-response relationships for LDL-C over a 16-week time course for LY3015014 • To assess the proportion of patients achieving an LDL-C level lower than 100 mg/dL (2.6 mmol/L) and lower than 70 mg/dL (1.8 mmol/L) for LY3015014 compared with placebo • To assess effects of LY3015014 in subgroups based on disease classification, region, diabetes status, statin dose, ezetimibe use, baseline LDL-C and PCSK9 levels, and prior exposure to PCSK9 antibodies on change in LDL-C • To assess other PD markers • To characterize the pharmacokinetic (PK) profile of LY3015014 • To assess the safety and tolerability of LY3015014, including muscle, hepatic and cardiovascular safety ;Primary end point(s): Low-density lipoprotein cholesterol (LDL-C) by beta quantification will be measured;Timepoint(s) of evaluation of this end point: Baseline and end of 16 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Lipid and apolipoprotein panel: including TG, TC, HDL C, LDL-C (calculated), apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B), lipoprotein(a) (Lp[a]) • Serum total PCSK9 and free PCSK9;Timepoint(s) of evaluation of this end point: At baseline and at various visits occurring every 2 weeks during the 16 week treatment period, and during the follow up period occurring every 4 weeks for a total of 8 weeks. | — |
Countries
Canada, Czech Republic, Denmark, Japan, Netherlands, Poland, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed