A Study of LY2484595 in Japanese Subjects
Condition: Dyslipidemias
MeSH terms: Dyslipidemias
Intervention: LY2484595; Placebo; Atorvastatin
Intervention description: Administered orally; Administered orally; Administered orally
Intervention MeSH terms: Atorvastatin; Evacetrapib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 165.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if 12 weeks of treatment with LY2484595
      administered as a monotherapy will significantly increase high-density lipoprotein
      cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) in Japanese
      participants.
    

Eligibility criteria:

        Inclusion Criteria:

        Have Low HDL-C or High LDL-C criteria as follows:

        Low HDL lipid criteria:

          -  HDL-C <45 milligrams per deciliter (mg/dL) (men) and <50 mg/dL (women), and

          -  LDL-C according to Japan Atherosclerosis Society (JAS) guidelines as follows:

               -  LDL-C <190 mg/dL (0-1 risk factors)

               -  LDL-C <160 mg/dL (2 risk factors)

               -  LDL-C <130 mg/dL (3+ risk factors),and

          -  Fasting Triglycerides (TG) <400 mg/dL

        or

        High LDL-C lipid criteria:

          -  HDL-C <100 mg/dL, and

          -  LDL-C according to JAS guidelines as follows:

               -  LDL-C 100-190 mg/dL (0-1 risk factors)

               -  LDL-C 100-160 mg/dL (2 risk factors)

               -  LDL-C 100-130 mg/dL (3+ risk factors), and

          -  Fasting TG <400 mg/dL

        Note: Subjects with diabetes regarded as 3+ risk factors

          -  Male subjects: Agree to use a reliable method of birth control during the study (and
             for 2 weeks following the last dose of study drug)

          -  Female subjects: 1) Women not of childbearing potential due to surgical sterilization
             (at least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy or
             tubal ligation) confirmed by medical history, or menopause. Menopausal women include
             women with either a) spontaneous amenorrhea for at least 12 months, not induced by a
             medical condition such as anorexia nervosa and not taking medications during the
             amenorrhea that induced the amenorrhea [for example, oral contraceptives, hormones,
             gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators
             (SERMs), or chemotherapy] or b) spontaneous amenorrhea for 6 to 12 months and a
             follicle-stimulating hormone (FSH) level greater than 40 milli-international units per
             milliliter (mIU/mL). or, 2) Women of child bearing potential who test negative for
             pregnancy at the time of enrollment based on a urine or serum pregnancy test and agree
             to use a reliable method of birth control during the study and for 2 weeks following
             the last dose of study drug

          -  Have given informed consent to participate in the study

        Exclusion Criteria:

          -  At screening, are currently enrolled in, or discontinued within the last 30 days from,
             a clinical trial involving an investigational product or unapproved use of a drug or
             device (other than the investigational product used in this study), or concurrently
             enrolled in any other type of medical research judged not to be scientifically or
             medically compatible with this study

          -  Have participated within 90 days prior to screening in any clinical trials of
             cholesteryl ester transfer protein (CETP) inhibitors (e.g., anacetrapib or
             dalcetrapib)

          -  Have completed or withdrawn from this study or have completed or withdrawn from any
             other study investigating LY2484595

          -  Are unable, unreliable, and/or unwilling to provide informed consent, make themselves
             available for the duration of the study, or will not abide by the procedures and study
             restrictions

          -  Have recent history of any clinically significant rash, history of any clinically
             severe drug-related rash, history of a chronic skin disorder (such as psoriasis,
             eczema or urticaria), history of significant skin hypersensitivities to household or
             cosmetic products, or allergens per the investigator, or presence of widespread
             tattoos or other skin condition that limits the assessment for rashes. Subjects who
             develop any rash during the Diet Lead-in/Washout Phase cannot be randomized

          -  Have or have had any clinical manifestation of coronary heart disease (CHD), such as
             stable or unstable angina, acute coronary syndrome, myocardial infarction, or a
             coronary revascularization procedure including stent placement, symptomatic carotid
             artery disease or symptomatic peripheral arterial disease. Subjects with a diagnosis
             of abdominal aortic aneurysm are excluded from this study

          -  Have systolic blood pressure (SBP) >140 millimeters of mercury (mm Hg) or diastolic
             blood pressure (DBP) >90 mm Hg as determined by the mean of 3 standardized
             measurements in the sitting position at randomization

          -  Have or have had documented hyperaldosteronism

          -  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) <35%. The absence of LVEF measurement does not prohibit entry
             into this study

          -  Have one of the following abnormalities: QTc prolongation [Bazett's corrected QT
             interval (QTcB)] of >450 msec in male subjects or >470 msec in female subjects, or
             abnormally wide QRS complexes (resulting from bundle branch blocks, intraventricular
             conduction delays, or pacemakers) or atrial fibrillation on screening
             electrocardiogram (ECG), previous history of QTc prolongation with another medication
             that required discontinuation, congenital long QT syndrome, previous history of
             ventricular tachycardia or unexplained syncope

          -  Have family history of long QT syndrome or sudden death likely secondary to
             ventricular arrhythmia

          -  Have active hepatobiliary disease, serologic evidence of past or active hepatitis B or
             C, or past or active gallbladder disease. Subjects who have been diagnosed with
             Gilbert syndrome or had a cholecystectomy greater than 90 days prior to screening can
             be included

          -  Have aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT),
             alkaline phosphatase (ALP), or total bilirubin >1.5 times the upper limit of normal
             (ULN)

          -  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) ≥3 times the ULN

          -  Have a history of discontinuation from statin, change of statin, or a dose reduction
             of statin due to history of hypersensitivity, intolerance or adverse effect. Have a
             history of increased hepatic enzymes associated with use of an
             hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin)

          -  Have a history of hypersensitivity or intolerance to drug preparations containing
             cholesteryl ester transfer protein (CETP) inhibitors, including but not limited to
             torcetrapib, anacetrapib, or dalcetrapib

          -  Have a hemoglobin A1c ≥8.0%; or use, plan to use, or are likely to require insulin
             during the course of the study. Diabetic subjects on an antidiabetic agent with lipid
             modifying effects must be on a stable dose for at least 30 days prior to screening

          -  Have a serum creatinine ≥2 mg/dL, or nephrotic syndrome, end stage renal disease and
             use renal replacement therapy such as hemodialysis or peritoneal dialysis

          -  Have hemoglobin <10 grams per deciliter (g/dL) in women and <11 g/dL in men

          -  Have current uncontrolled active inflammatory condition or infection which in the
             opinion of the investigator would influence a subject's ability to complete the study

          -  Have thyroid-stimulating hormone (TSH) levels outside normal reference range. Subjects
             who are clinically euthyroid, on stable thyroid replacement therapy for 60 days prior
             to screening, and are anticipated to remain on this dose throughout the trial period
             are acceptable exceptions to this criterion

          -  Are women who are lactating

          -  Have planned or are likely to require major surgery requiring anesthesia or
             hospitalization during the course of the study

          -  Have chronic alcohol or drug abuse or dependency

          -  Are currently under suspicion of having cancer or have had a history of cancer in the
             past 2 years, with the exception of excised superficial lesions such as basal cell
             carcinoma and squamous cell carcinoma of the skin

          -  Have history of human immunodeficiency virus (HIV) infection

          -  Have any other condition or abnormal laboratory value, which in the opinion of the
             investigator precludes the subject from providing informed consent

          -  Plan to use, are likely to require, or unwilling or unable to stop with adequate
             washout any prescription or over-the-counter (OTC) medication or health foods with the
             intent to treat serum lipids (LDL-C, HDL-C, triglycerides) including but not limited
             to these classes of drugs: statin, ezetimibe, bile acid sequestrant, eicosapentaenoic
             acid (EPA). Subjects taking probucol, fibrate or nicotinic agents within 8 weeks
             before screening are excluded from the study

          -  Are currently using, plan to use, or are likely to require during the course of the
             study systemic corticosteroids; or anabolic agents other than stable doses of
             estrogen, estrogen/progestin, or testosterone replacement therapy

          -  Are currently using, plan to use, or are likely to require during the course of the
             study, more than the occasional use (i.e., once every other week) of stimulant
             laxatives (e.g., bisacodyl), osmotic laxatives (e.g., milk of magnesia), or castor oil

          -  Use of any immunosuppressive therapy within 60 days prior to screening or are likely
             to require immunosuppressive therapy during the course of the study

          -  Have received treatment within 30 days prior to the time of study entry with any drug
             or drugs that have not received regulatory approval for any indication

          -  Have plans to adopt diets with aggressive carbohydrate restrictions for weight loss.
             Currently use, have used within 60 days prior to screening, or plan to use during the
             trial period prescriptions or OTC formulations intended for weight loss

          -  Are currently using, have used within 60 days prior to screening, plan to use, or are
             likely to require during the course of the study, drugs or foods that are inducers
             (including rifampin and carbamazepine) or moderate or strong inhibitors of cytochrome
             P450 3A (including, ketoconazole, erythromycin and grapefruit juice); or strong
             inhibitors of the organic anion transporter polypeptide 1B1 (OATP1B1) transporter
             (including cyclosporine and rifampin). The drugs used in topical preparations are
             acceptable