A Phase 2 Efficacy and Safety Dose-Ranging Study of LY3015014 in Patients with Primary Hypercholesterolemia

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 80

Inclusion Criteria

[1] Are men or women *18 years of age and *80 years of age.;[2] Diagnosed with primary HC defined as LDL-C *100 mg/dL (2.6 mmol/L) and TG *450 mg/dL (5.1 mmol/L).
o A subset of patients (up to approximately 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 approximately 20% HeFH patients with probable or definite diagnosis
based on clinical criteria or genotype (see Manual of Operations [MOO]) and polygenic
(non-familial) HC patients.;[3] Are on a stable diet and stable daily dose of atorvastatin, simvastatin (*40 mg/day),
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
approximately 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.;[4a] 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.;[4b] Female patients, including:
1) Women not of childbearing 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 acessation 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.
2) Women of childbearing 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 (that is, <1% per year) when used consistently and correctly. For example:
* Combination oral contraceptive pill
* Implantable contraceptives
* Injectable contraceptives
* Intrauterine device
* Intrauterine system * for example, Mirena progestin-releasing coil
* Contraceptive patch
See MOO for additional information regarding reliable methods of birth control.
[5] Have given informed consent to participate in the study.

Exclusion Criteria

[6] Have secondary HC or homozygous familial HC. ;[7] 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.;[8] 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%.;[9] Uncontrolled hypertension characterized by a systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg.;[10] 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%.;[11] 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 2 months prior to screening and who are anticipated to remain on this dose throughout the trial period are acceptable exceptions to this criterion.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to assess the mean percentage change<br /><br>from baseline to week 16 in low-density lipoprotein cholesterol (LDL-C)<br /><br>measured using beta quantification with LY3015014 compared with placebo, in<br /><br>patients with primary hypercholesterolemia (HC), when added to statin and diet<br /><br>(or diet alone in statin-intolerant patients) with or without ezetimibe. </p><br>

Secondary Outcome Measures

Name	Time	Method

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