Study of the Safety, and efficacy after Multiple Dosing in Diabetic Patients
- Conditions
- Chronic kidney disease associated with Diabetic nephropathyMedDRA version: 16.1Level: LLTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 100000004857MedDRA version: 16.1Level: LLTClassification code 10012678Term: Diabetic nephropathy NOSSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]
- Registration Number
- EUCTR2012-004496-40-BG
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 64
1. Stable DKD while taking SOC, as defined by:
a. Estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2 as determined utilizing the Modification of Diet in Renal Disease (MDRD) equation (Levey et al. 2006)
b. Taking ACE inhibitor or ARB at a stable dose for = 2 months prior to randomization and agree to continue to take such throughout the duration of the study
c. Type 1 or Type 2 diabetes on a stable treatment regimen and adequately controlled in opinion of investigator
d. First morning protein creatinine ratio (PCR) at screening = 400 mg/g (Part B only)
2. Clinical chemistry labs within acceptable range for the patient population, as per investigator judgment
3. Men and women of non-childbearing potential as determined by medical history.
a. Non-vasectomized male patients 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.
b. Female patients must be postmenopausal or surgically sterile to particpate in this study. Postmenopausal is defined as females between age 45 to 65 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 FSH >40 IU/L
4. 18-75 years old, inclusive and must weigh = 50 kg at time of screening and dosing.
5. Acceptable sitting blood pressure (systolic blood pressure [SBP] <140 mmHg and diastolic blood pressure [DBP] < 90 mmHg on most occasions). Stage I BP elevation (SBP 140-159 or DBP 90-99) on some occasions may be acceptable, as long as only non-protein-lowering antihypertensives are adjusted to achieve target BP goals (<140/90). Based on possible proteinuria effects, the doses of ACEi/ARBs, diltiazem, verapamil, and amlodipine may not be adjusted during the study. Acceptable antihypertensives for adjustment during the study may include nifedipine, felodipine, diuretics, beta-adrenergic antagonists, and other agents not known to affect urinary protein per investigator judgment.
6. Have given written informed consent prior to any study-specific procedures.
7. Are reliable and willing to make themselves available for the duration of the study and are willing to follow site specific study procedures.
8. Have venous access sufficient to allow blood sampling as per the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24
1. Patients with diagnosis of CKD other than DKD (hypertensive nephrosclerosis superimposed on DKD is acceptable)
2. Patients with SBP >160 mmHg or DBP >100 mmHg, despite adjustment of the antihypertensive regimen, confirmed upon repeat assessment
3. Patients with current use of (or within 2 weeks of enrollment), or projected need for a renin inhibitor or aldosterone antagonist, or a combination of ACEi/ARB or medications that confound the assessment of renal function, including lithium, immunosuppressives, anti-vascular endothelial growth factor (VEGF) therapies, and chronic nonsteroidal anti-inflammatory drugs (NSAIDs); Patients who are unwilling to discontinue use of any medication with potential to mask a significant allergic response (e.g. systemic glucocorticoids) within 3 days of dosing;
4. Patients in whom dialysis or transplantation is anticipated within 6 months of screening
5. Patients with history of acute kidney injury within 3 months of screening
6. Patients who 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
7. Patients who have previously completed or withdrawn from this study or any other study investigating LY3016859
8. Patients with a diagnosis of Class III or IV congestive heart failure (as defined by the New York Heart Association); active/significant skin disorders (dermatitis, rash, acne, psoriasis), lung diseases (asthma, COPD, interstitial lung disease), or ocular disorders affecting sclerae, conjunctiva or iris (scleritis, conjunctivitis, keratoconjunctivitis, uveitis).
9. Patients with an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study. In addition, subjects with the following findings will be excluded:
a. Confirmed corrected QT (QTcF) interval > 450 msec for men and > 470 msec for women; additional ECGs may be performed if required
b. Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular ectopic beats
c. History of unexplained syncope
d. Family history of unexplained sudden death or sudden death due to long QT syndrome
e. T-wave configurations are not of sufficient quality for assessing QT interval, as determined by the investigator
10. Patients with evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies; patients with a history of cirrhosis or hepatitis C or are positive for hepatitis C antibody at the screening visit; patients who are known to be hepatitis B surface antigen-positive or are positive for hepatitis B surface antigen at the screening visit
11. Patients who are unwilling to discontinue use of Chinese herbs for at least 2 weeks prior to randomization and for the duration of their study participation.
12. Patients who are investigator site personnel directly affiliated with this study and/or members of their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
13. Patients who are Lilly or Chorus employees or contractors or their immediate family members
14. Patients who are unwilling or unable to comply with the use of a data collection device to di
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •To investigate the safety and tolerability of multiple IV doses of LY3016859 in DN patients <br>•To evaluate the effect of multiple IV dosing of LY3016859 on change from baseline in proteinuria at 16 weeks in DN patients (Part B only) <br>;Secondary Objective: •To investigate the effect of LY3016859 on change from baseline in proteinuria and albuminuria over time (Part B only);Primary end point(s): Number of participants with clinically significant effects (Parts A and B) and change from baseline in proteinuria (Part B);Timepoint(s) of evaluation of this end point: Safety: Baseline to 6 and 12 weeks post last dose for Parts A and B, respectively; Proteinuria: Baseline to 16 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Change from baseline in proteinuria and albuminuria;Timepoint(s) of evaluation of this end point: Baseline to 16 weeks