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A Study to Test Safety and Efficacy of Baricitinib in Participants With Diabetic Kidney Disease

Phase 2
Completed
Conditions
Diabetic Kidney Disease
Interventions
Drug: Placebo
Registration Number
NCT01683409
Lead Sponsor
Eli Lilly and Company
Brief Summary

This is a dose ranging study to evaluate the safety and efficacy of baricitinib in the treatment of participants with mild to moderate diabetic kidney disease.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
Inclusion Criteria
  • Participants with Type 2 diabetes treated with at least one antihyperglycemic medicine for 12 months
  • Have diabetic kidney disease and receiving one of two specific medicines used to treat high blood pressure or diabetic kidney disease for at least 3 months
  • Estimated Glomerular Filtration Rate (eGFR) of 25 to 70 milliliter per minute per 1.73 square meter (mL/min/1.73 m²) (as determined by the Chronic Kidney Disease Epidemiology Collaboration equation) and a urinary albumin/creatinine ratio (UACR) >300 milligram per gram (mg/g) and <5000 mg/g
Exclusion Criteria
  • Too high blood pressure when you enter the study
  • Some specific medicines used to treat high blood pressure or diabetic kidney disease
  • Frequent high blood glucose levels
  • Renal transplant or past history of dialysis
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Had a special X-ray in the past 30 days which involved also receiving an injection of dye into the vein
  • Major surgery within 8 weeks of study entry or will require major surgery during the study
  • Some types of vaccination
  • Shingles or currently have symptoms of a cold sore
  • Serious viral, bacterial, fungal, or parasitic infection, or a urinary infection, Tuberculosis (TB)
  • Human immunodeficiency virus (HIV) infection- the virus that causes Acquired immunodeficiency syndrome (AIDS)
  • Have or had some blood disorders, enlarged lymph glands or spleen, or some cancers.
  • Serious circulatory, breathing, liver, stomach or bowel problems, neurological or psychiatric disorders
  • Heart attack or heart failure, or a stroke
  • Other serious disorders or illnesses
  • Electrocardiogram (ECG) heart trace abnormalities
  • Alcohol or illegal drug abuse
  • Donated more than 500 mL of blood in the last 30 days (no blood donations allowed during the study)
  • Pregnant or breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Baricitinib 0.75 mg/0.5 mg QDBaricitinibAdministered orally, 0.75 mg given as one 0.75 mg tablets and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks or 0.5 mg given as one 0.5 mg tablet and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind.
Baricitinib 0.75 mg/0.5 mg BIDPlaceboAdministered orally, 0.75 mg given as one 0.75 tablet and 2 placebo in the morning and one 0.75 mg tablet in the evening for 24 weeks or 0.5 mg given as one 0.5 mg tablet and two placebo tablets in the morning and one 0.5 mg tablet in the evening. Placebo tablets given to maintain blind.
Baricitinib 0.75 mg/0.5 mg QDPlaceboAdministered orally, 0.75 mg given as one 0.75 mg tablets and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks or 0.5 mg given as one 0.5 mg tablet and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind.
Baricitinib 1.5 mg/1 mgPlaceboAdministered orally, 1.5 mg given as two 0.75 mg tablets and 1 placebo tablet in the morning and one placebo tablet in the evening for 24 weeks or 1 mg tablet and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind.
Baricitinib 4 mg/2.75 mgPlaceboAdministered orally, 4 mg given as one tablet and 2 placebo tablets in the morning and one placebo tablet in the evening for 24 weeks or 2.75 mg given as two 1 mg tablets and one 0.75 mg tablet in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind.
PlaceboPlaceboAdministered orally, given as three placebo tablets in the morning and one placebo tablet in the evening for 24 weeks.
Baricitinib 0.75 mg/0.5 mg BIDBaricitinibAdministered orally, 0.75 mg given as one 0.75 tablet and 2 placebo in the morning and one 0.75 mg tablet in the evening for 24 weeks or 0.5 mg given as one 0.5 mg tablet and two placebo tablets in the morning and one 0.5 mg tablet in the evening. Placebo tablets given to maintain blind.
Baricitinib 1.5 mg/1 mgBaricitinibAdministered orally, 1.5 mg given as two 0.75 mg tablets and 1 placebo tablet in the morning and one placebo tablet in the evening for 24 weeks or 1 mg tablet and two placebo tablets in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind.
Baricitinib 4 mg/2.75 mgBaricitinibAdministered orally, 4 mg given as one tablet and 2 placebo tablets in the morning and one placebo tablet in the evening for 24 weeks or 2.75 mg given as two 1 mg tablets and one 0.75 mg tablet in the morning and one placebo tablet in the evening for 24 weeks. Placebo tablets given to maintain blind.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Urinary Albumin/Creatinine Ratio (UACR) at Week 24Baseline, Week 24

UACR is a potential marker of chronic kidney disease, calculated as a ratio of Urinary Albumin and Urinary Creatinine. The least squares mean (LS mean) are from mixed model repeated measures (MMRM) analyses which include treatment, baseline estimated Glomerular Filtration Rate (eGFR) group (higher: 50 to 70 mL/min/1.73m² and lower: 25 to \<50 mL/min/1.73m²), visit, treatment-by-visit interaction, baseline UACR, and baseline UACR-by-visit interaction.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 24Baseline, Week 24

EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. The LS means are analyzed using an analysis of covariance (ANCOVA) model with treatment, baseline eGFR group, and baseline VAS score or baseline health state index score as covariates.

Change From Baseline in Urinary Monocyte Chemotactic Protein 1 (MCP-1)/Creatinine RatioBaseline, Week 24
Change From Baseline in Creatinine Clearance at Week 24Baseline, Week 24

Creatinine clearance is the amount of creatinine cleared from kidney within 24 hours. The LS mean was from MMRM analyses which included treatment, baseline eGRF group, visit, treatment-by-visit interaction, baseline Creatinine Clearance, and baseline Creatinine Clearance-by-visit interaction.

Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady State (AUC,ss)Weeks 2 and 4 (1-2 hours postdose), 8 (3-6 hours postdose), 12 (in fasted state), 16 and 20 (6-9 hours postdose), 24 (in fasted state)

Evaluable pharmacokinetic concentrations from the 2-week, 4-week, 8-week, 12-week, 16-week, 20-week and 24-week time points were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.

Trial Locations

Locations (1)

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.

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