AzTrials
AzTrials

DyslipidemiasPhase 2NCT01375075

A Study of LY2484595 in Japanese Subjects

A Phase 2 study testing LY2484595 and Atorvastatin in people with Dyslipidemias, run by Eli Lilly and Company at 5 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Dyslipidemias
What is being tested?
LY2484595 and Atorvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
165 participants
Where
5 sitesJapan
Study dates
Jun 2011to Mar 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 20Show fewer
  • 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

Who cannot join

  • 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
Show all 34Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Japan5 sites

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Hyōgo, 660-0814

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Kanagawa, 231-0023

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Kyoto, 615-8125

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Osaka, 560-0005

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Tokyo, 111-0052

Other trials in Japan

About this study

Official title: A Phase 2 Dose Response Study of LY2484595 in Japanese Subjects

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.

Conditions
Dyslipidemias
Being tested
LY2484595, Placebo, Atorvastatin
Medical subject headings
Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY2484595Drug

    Administered orally

  • PlaceboDrug

    Administered orally

  • AtorvastatinDrug

    Administered orally

Study groups in NCT01375075
Study groupRoleWhat they receive
30 milligrams (mg) LY2484595ExperimentalAdministered orally once daily for 12 weeks
Receives: Drug: LY2484595; Drug: Placebo
100 mg LY2484595ExperimentalAdministered orally once daily for 12 weeks
Receives: Drug: LY2484595; Drug: Placebo
500 mg LY2484595ExperimentalAdministered orally once daily for 12 weeks
Receives: Drug: LY2484595; Drug: Placebo
PlaceboPlacebo comparatorAdministered orally once daily for 12 weeks
Receives: Drug: Placebo
10 mg AtorvastatinActive comparatorAdministered orally once daily for 12 weeks
Receives: Drug: Placebo; Drug: Atorvastatin
100 mg LY2484595 + 10 mg AtorvastatinExperimentalAdministered orally once daily for 12 weeks
Receives: Drug: LY2484595; Drug: Placebo; Drug: Atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline to 12 Weeks in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo

    Percent change from baseline = 100*(post-baseline assessment - baseline assessment)/baseline assessment. Higher values in the percent change from baseline represented an improvement for HDL-C and lower values in the percent change from baseline represented an improvement for LDL-C. Least Squares (LS) mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

Secondary outcomes (12)

  1. Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin

    Percent change from baseline = 100*(post-baseline assessment - baseline assessment)/baseline assessment. An increase in the percent change from baseline represented an improvement for HDL-C and a decrease in the percent change from baseline represents an improvement for LDL-C. LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline, Weeks 2, 4, and 8

  2. Pharmacokinetics - Area Under the Curve (AUC) of LY2484595 and Atorvastatin

    Measured: Weeks 2, 4, 8, 12 (predose and postdose), and Week 16

  3. The Number and Severity of Episodes of Rashes at Any Time From Baseline Through Week 12

    All rash cases were adjudicated by a central dermatologist blinded to treatment assignment according to a study-specific Clinical Events Committee (CEC) charter. Rash events were assessed according to clinical relevance (severity). Categories included high risk, low risk, not a relevant dermatosis, or insufficient documentation for determination. High risk rashes included anaphylaxis, toxic epidermal necrolysis, Stevens Johnson Syndrome, Drug Reaction with Eosinophilia and System Symptoms (DRESS), urticaria/angioedema, vasculitis, erythroderma, and lupus-like reaction. All other rashes were considered low risk or not a relevant dermatosis per the Investigator's clinical opinion. A participant could be reported in multiple categories.

    Measured: Baseline through Week 12

  4. Change From Baseline to 12 Weeks in Blood Pressure

    Blood pressure reported as systolic blood pressure (SBP) and diastolic blood pressure (DBP).

    LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

  5. Change From Baseline to 12 Weeks in Aldosterone

    LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

  6. Change From Baseline to 12 Weeks in Plasma Renin Activity

    LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

  7. Change From Baseline to 12 Weeks in Serum Sodium

    LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

  8. Change From Baseline to 12 Weeks in Serum Bicarbonate

    LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

  9. Number of Myopathy and Liver Injury Events

    Myopathy events were considered muscle-related treatment emergent adverse events (TEAEs) and liver injury events were considered hepatic disorder-related TEAEs reported per Medical Dictionary for Regulatory Activities (MedDRA). An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs were newly occurring AEs or AEs worsening after first dose.

    Measured: Baseline through Week 12

  10. Change From Baseline to 12 Week Endpoint in Highly-Sensitive C-Reactive Protein (hsCRP)

    LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline and Week 12

  11. Percent Change From Baseline in Plasma Cholesteryl Ester Transfer Protein (CETP) Activity

    Plasma CETP activity assay employed a fluorometric method to determine the CETP transfer activity. Percent change from baseline = 100*(post-baseline assessment - baseline assessment)/baseline assessment. An increase in the percent change from baseline represented an improvement. LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline, Weeks 4, 8, and 12

  12. Change From Baseline in Plasma CETP Mass

    Plasma CETP mass assay was a solid-phase enzyme-linked immunosorbent assay (ELISA) designated to measure human CETP mass which employed the quantitative enzyme immunoassay principle. An increase in plasma CETP mass represented an improvement. LS mean was adjusted for baseline value of the variable analyzed.

    Measured: Baseline, Weeks 4, 8, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionMar 2012
  4. Study completionMar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
165 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01375075
Sponsor's protocol ID
13049
Other IDs
I1V-JE-EIAE
Status last verified
Mar 2018
First submitted
15 Jun 2011
Last updated
25 Oct 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LY2484595 and Atorvastatin in people with Dyslipidemias, run by Eli Lilly and Company at 5 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline to 12 Weeks in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01375075.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in