Study of LY3016859 in Participants With Diabetic Nephropathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01774981
First received: January 22, 2013
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Diabetic Nephropathy
Drug: Placebo
Drug: LY3016859
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Study of the Safety and Efficacy of LY3016859 After Multiple Intravenous Dosing in Diabetic Nephropathy Patients

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Part B: Change from Baseline in Proteinuria [ Time Frame: Baseline, 16 Weeks ] [ Designated as safety issue: No ]
  • Part A and Part B: Number of Participants with One or More Treatment Emergent Adverse Events (AEs) or Any Serious AEs [ Time Frame: Baseline up to 32 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part B: Change from Baseline in Proteinuria Over Time [ Time Frame: Baseline up to 25 Weeks ] [ Designated as safety issue: No ]
  • Part B: Change from Baseline in Albuminuria Over Time [ Time Frame: Baseline up to 25 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: March 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo (Part A)
Placebo (Part A) administered by 60 minute Intravenous (IV) infusion at Week 1 and Week 4.
Drug: Placebo
Administered IV
Experimental: 10 mg LY3016859 (Part A)
10 milligram (mg) LY3016859 administered by 60 minute IV infusion at Week 1 and Week 4.
Drug: LY3016859
Administered IV
Experimental: 100 mg LY3016859 (Part A)
100 mg LY3016859 administered by 60 minute IV infusion at Week 1 and Week 4.
Drug: LY3016859
Administered IV
Experimental: 750 mg LY3016859 (Part A)
750 mg LY3016859 administered by 60 minute IV infusion at Week 1 and Week 4.
Drug: LY3016859
Administered IV
Placebo Comparator: Placebo (Part B)
Placebo (Part B) administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.
Drug: Placebo
Administered IV
Experimental: Low Dose LY3016859 (Part B)
Low Dose LY3016859 from Part A administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.
Drug: LY3016859
Administered IV
Experimental: Middle Dose LY3016859 (Part B)
Middle Dose LY3016859 from Part A administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.
Drug: LY3016859
Administered IV
Experimental: Maximum Dose LY3016859 (Part B)
Maximum Dose LY3016859 from Part A administered by 60 minute IV infusion at Weeks 1, 4, 7, 10 and 13.
Drug: LY3016859
Administered IV

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01774981

Contacts
Contact: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, Florida
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. Recruiting
Clearwater, Florida, United States, 33756
Contact: Eli Lilly         
United States, Nebraska
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. Active, not recruiting
Omaha, Nebraska, United States, 68131
United States, Pennsylvania
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. Recruiting
Bethlehem, Pennsylvania, United States, 18017
Contact: Eli Lilly         
United States, Tennessee
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. Recruiting
Chattanooga, Tennessee, United States, 37408
Contact: Eli Lilly         
United States, Texas
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. Recruiting
Lufkin, Texas, United States, 75904
Contact: Eli Lilly         
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. Recruiting
San Antonio, Texas, United States, 78215
Contact: Eli Lilly         
Bulgaria
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. Recruiting
Sofia, Bulgaria, 1612
Contact: Eli Lilly         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLilly (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST_ Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01774981     History of Changes
Other Study ID Numbers: 14353, I5V-MC-TGAB, 2011-005596-17
Study First Received: January 22, 2013
Last Updated: September 19, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on October 20, 2014