Diabetic Nephropathy MedDRA version: 14.1 Level: PT Classification code 10061835 Term: Diabetic nephropathy System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: CCX140-B
Product Code: CCX140-B
Pharmaceutical Form: Capsule, hard
Current Sponsor code: CCX140-B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Sponsors
ChemoCentryx, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female, aged 18-75 years inclusive, with documented previously diagnosed type 2 diabetes mellitus (per American Diabetes Association [ADA] criteria); 2.Residual albuminuria despite stable ACE inhibitor or ARB therapy for at least 8 weeks prior to screening (ACR of 100 to 3000 mg albumin/g creatinine, inclusive, based on two values obtained from two first morning urine samples taken on two separate days during the screening period; both ACR values must be 100 to 3000 mg albumin/g creatinine, inclusive); 3.Estimated glomerular filtration rate based on serum creatinine (eGFR, determined by Modification of Diet in Renal Disease [MDRD] equation) of = 25 mL/min/1.73 m2 based on two values obtained from two blood samples taken on two separate days during the screening period; both eGFR values must be = 25 mL/min/1.73 m2; 4.Must have been on a stable dose of either an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) for at least 8 weeks prior to screening. The dose of these drugs must not be lower than the lowest labeled dose. Subjects may not be on both an ACE inhibitor and an ARB. Doses of any other anti-hypertension treatment must have been stable for at least 4 weeks prior to screening; 5.Any anti-diabetic treatment must have been maintained at stable dose(s) for at least 8 weeks prior to screening; 6.If on any lipid lowering drug, the subject must have been on a stable dose for at least 4 weeks prior to screening; 7.If taking any phosphate binders, cinacalcet, vitamin D or vitamin D analogues, must have been on stable doses for at least 4 weeks prior to screening; 8.Hemoglobin A1c (HbA1c) > 6.0% but not > 10.0% and fasting plasma glucose less than 270 mg/dL at screening; 9.Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; 10.Judged to be otherwise healthy by the Investigator, based on medical history, physical examination (including electrocardiogram [ECG]), and clinical laboratory assessments. Subjects with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study; and 11.Female subjects of childbearing potential, and male subjects with partners of childbearing potential, may participate if adequate contraception is used during, and for at least the four weeks after, any administration of study medication. Adequate contraception is defined as usage by at least one of the partners of a barrier method of contraception, together with usage by the female partner, commencing at least three months prior to Screening, of a stable regimen of any form of hormonal contraception or an intra-uterine device. Use of abstinence alone is not considered adequate. Use of a barrier method alone is considered adequate only if the male partner was vasectomized at least six months prior to Screening. Use of a double-barrier method of contraception is acceptable. Women of childbearing potential must have a negative serum pregnancy test during the screening period and a negative urine pregnancy test on the day of initial dosing. 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 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subject
Exclusion criteria
Exclusion criteria: 1.Type 1 diabetes mellitus or history of diabetic ketoacidosis; 2.Previous renal transplant or known non-diabetic renal disease, except related to hypertension; 3.Has undergone renal dialysis at any time in the past; 4.Women who are pregnant or breastfeeding; 5.Body mass index (BMI) above 45.4 kg/m2; 6.Received chronic (more than 7 days continuously) systemic glucocorticoid or other immunosuppressive treatment within 8 weeks prior to screening; 7.Use of bardoxolone, atrasentan or other endothelin antagonist within 8 weeks prior to screening; 8.Received chronic (more than 7 days continuously) NSAID treatment within 2 weeks prior to screening; 9.Cardiac failure (class III or IV), history of unstable angina, symptomatic coronary artery disease, myocardial infarction or stroke within 12 weeks prior to screening; 10.Poorly-controlled blood pressure (systolic blood pressure >155 or diastolic blood pressure >95, with blood pressure measured in the seated position after at least 5 minutes of rest); 11.History of hypersensitivity to ingredients of the placebo (tartrazine, microcrystalline cellulose, starch, or croscarmellose sodium); 12.History or presence of leukopenia (WBC count 2 x the upper limit of normal; 21.Clinically significant abnormal ECG during screening, e.g., QTc greater than 450 msec; 22.Participated in any clinical study of an investigational product within 30 days prior to randomization; and 23.History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary safety objective is to evaluate the safety and tolerability of CCX140-B, based on subject incidence of adverse events over 52 weeks of treatment, in subjects with diabetic nephropathy (DN). Primary efficacy objective is to evaluate the efficacy of CCX140-B, compared to placebo, over 52 weeks of placebo-controlled treatment based on changes from baseline in first morning urinary albumin:creatinine ratio (ACR);Secondary Objective: Evaluation of the efficacy of CCX140-B, compared to placebo, based on changes from baseline in: 1. Estimated glomerular filtration rate (eGFR) and 2. Hemoglobin A1c (HbA1c) Other study objectives include: 1.Evaluation of the effect of CCX140-B on other renal parameters including estimated glomerular filtration rate (eGFR), serum creatinine, blood urea nitrogen (BUN), and serum phosphorus; 2.Evaluation of the effect of CCX140-B on fasting plasma glucose (FPG), fasting plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR); 3.Evaluation of the effect of CCX140-B treatment on urinary monocyte chemoattractant protein-1 (MCP-1):creatinine ratio and plasma MCP-1 concentrations; 4.Evaluation of the safety of CCX140-B based on changes in safety laboratory parameters, vital signs, and physical examination findings; and 5.Assessment of plasma concentration profile of CCX140 and possible metabolites in subjects with DN.;Primary end point(s): Efficacy end piont: Percent change of morning urinary ACR Safety end point: Nature, frequency and severity of adverse events;Timepoint(s) of evaluation of this end point: Day 1 through Day 365 days (52 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints : Changes is eGFR Other end points 1. Serum creatinine, BUN and serum phosphorus 2. Fasting plasma glucose, insulin, and HOMA-IR; and 3. Urinary MCP-1: creatinine ratio and plasma MCP-1 PK analysis;Timepoint(s) of evaluation of this end point: Day 1 through Day 365 (52weeks) PK - Day 1 through Day 393 | — |
Countries
Belgium, Czech Republic, Germany, Hungary, United Kingdom
Contacts
Public ContactMedpace Regulatory Submissions
Medpace
Outcome results
None listed