Study of LY3016859 in Participants With Diabetic Nephropathy



Status:Completed
Conditions:Diabetic Neuropathy, Renal Impairment / Chronic Kidney Disease
Therapuetic Areas:Endocrinology, Nephrology / Urology
Healthy:No
Age Range:18 - 75
Updated:10/8/2017
Start Date:March 2013
End Date:August 2015

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Study of the Safety and Efficacy of LY3016859 After Multiple Intravenous Dosing in Diabetic Nephropathy Patients

The purpose of this two-part study is to investigate the safety, tolerability and efficacy of
LY3016859 after multiple intravenous (IV) dosing's in participants with diabetic nephropathy
(DN). Part A will be dose escalation for safety and tolerability and Part B will evaluate
Proteinuria.


Inclusion Criteria:

- Stable diabetic kidney disease (DKD) while taking Standard of Care medication (SOC),
as defined by:

- Estimated glomerular filtration rate (eGFR) less than (<) 90 milliliter per
minute per 1.73 square meter (ml/min/1.73m²) as determine utilizing the
Modification of Diet in Renal Disease (MDRD) equation

- Taking an angiotensin convertible enzyme (ACE) inhibitor or angiotensin II
receptor blocker (ARB) at a stable dose for greater than or equal to (≥) 2 months
prior to randomization and agree to continue to take such throughout the duration
of the study

- Type 1 or Type 2 diabetes on a stable treatment regimen and adequately controlled
in the opinion of the investigator

- First morning protein-creatine ratio (PCR) at screening ≥400 milligrams per gram
(mg/g) (Part B only)

- Clinical chemistry labs within acceptable range for the participant population, as per
investigator judgment

- Men and women of non-childbearing potential as determined by medical history and
physical examination

- Non-vasectomized male participants must agree to use a medically accepted method
of contraception with all sexual partners during the study and for 90 days
following the final dosing. Medically accepted effective forms of contraception
may include condoms with contraceptive foam or having partners use diaphragms
with contraceptive jelly or cervical caps with contraceptive jelly

- Female participants must be postmenopausal or surgically sterile to participate
in this study. This is defined as females between age 45 to 75 years, inclusive,
and either 12 months without a menstrual period [no follicle stimulating hormone
(FSH) test required] or 6-12 months without a menstrual period and follicle
stimulating hormone (FSH) greater than (>) 40 international units per liter
(IU/L)

- Must weigh ≥50 kilograms (kg) at time of screening and dosing

- Acceptable sitting blood pressure (BP) per the following American Heart Association
(AHA) guidelines:

- Normal: systolic blood pressure (SBP) <120 millimeters of mercury (mmHg) and
diastolic blood pressure (DBP) <80 mmHg

- Prehypertension: SBP 120-139 or DBP 80-89

- High Blood Pressure (Hypertension) Stage 1: SBP 140-159 mmHg or DBP 90-99

- Have given written informed consent prior to any study-specific procedures

- Are reliable and willing to make themselves available for the duration of the study
and are willing to follow site specific study procedures

- Have venous access sufficient to allow blood sampling

- Have laboratory values and other safety parameters that are, in the opinion of the
investigator, acceptable fo participation for the study

Exclusion Criteria:

- Have a diagnosis of chronic kidney disease (CKD) other than DKD, (hypertensive
nephrosclerosis superimposed on DKD is acceptable)

- Have SBP >160 mmHg or DBP >100 mmHg

o Individuals with Stage 1 BP elevation (SBP 140-159 mmHg or DBP 90-99 mmHg) on some
occasions during study, may be acceptable, as long as only non-protein-lowering
antihypertensives are adjusted to achieve target BP goals (<140/90 mmHg)

- Current use of (or within 2 weeks of enrollment), or projected need for a renin
inhibitor or aldosterone antagonist, or a combination of Angiotensin-converting enzyme
inhibitors/angiotensin II receptor blockers (ACEi/ARB)

- Individuals in whom dialysis or transplantation is anticipated within 6 months of
screening

- Have a history of acute kidney injury within 3 months of screening

- Are currently enrolled in, or discontinued within the last 60 days from, a clinical
trial involving an investigational drug that has not received regulatory approval for
any indication and/or have received treatment with biologic agents (such as monoclonal
antibodies) within 3 months or 5 half-lives of the administered drug (whichever is
longer) prior to dosing

- Have previously completed or withdrawn from this study or any other study
investigating LY3016859

- Have a diagnosis of Class III or IV congestive heart failure (as defined by the New
York Heart Association)

- Have an abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the
investigator increases the risks associated with participating in the study. In
addition, individuals with the following findings will be excluded:

- Confirmed corrected QT (QTcF) interval >450 milliseconds (msec) for men and >470
msec for women

- Irregular rhythms other than sinus arrhythmia or occasional, rare
supraventricular ectopic beats

- History of unexplained syncope

- Family history of unexplained sudden death or sudden death due to long QT
syndrome

- T-wave configurations are not of sufficient quality for assessing QT interval, as
determined by the investigator

- Have evidence of human immunodeficiency virus (HIV) and/or positive human HIV
antibodies; have a history of cirrhosis or hepatitis C or are positive for hepatitis C
antibody at the screening visit; are known to be hepatitis B surface antigen-positive
or are positive for hepatitis B surface antigen at the screening visit

- Are unwilling to discontinue use of Chinese herbs for at least 2 weeks prior to
randomization and for the duration of their study participation

- Are unwilling or unable to comply with the use of a data collection device to directly
record data from the participant

- Have donated blood of more than 500 milliliters (mL) within the last 60 days prior to
screening

- Have an average weekly alcohol intake that exceeds 21 units per week or are unwilling
to stop alcohol intake within 48 hours of entry into study and for the duration of the
study (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45
mL of distilled spirits)

- Individuals who, in the opinion of the investigator, show evidence of regular use of
drugs of abuse
We found this trial at
7
sites
Clearwater, Florida 33756
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Bethlehem, Pennsylvania 18017
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Bethlehem, PA
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Chattanooga, Tennessee 37404
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Lufkin, Texas 75904
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Lufkin, TX
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601 N 30th St
Omaha, Nebraska 68131
(402) 449-4000
Creighton University Medical Center St. Joseph's Mercy Hospital was founded on September 25, 1870 at...
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Omaha, NE
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San Antonio, Texas
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San Antonio, TX
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Sofia,
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