The primary efficacy objective of this study is to evaluate the effect of CCX140-B treatment on urinary albumin excretion in subjects with type 2 diabetes mellitus (T2DM) with albuminuria.The primary safety objective of this study is to evaluate the…
ID
Source
Brief title
Condition
- Diabetic complications
- Diabetic complications
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Urinary albumin excretion
Safety and tolerability
Secondary outcome
HbA1c
PK-parameters
Creatinine (serum, urine, clearance), blood urea nitrogen, phosphorus
Urinary MCP-1:creatinine ratio, and other serum and urinary markers of renal
function and inflammation
Background summary
Type 2 diabetes mellitus has reached epidemic proportions in the western world,
and its complications are severe and disabling. One of those complications is
nephropathy, slowly progressing to end stage renal failure, despite
ACE-inhibitors and other therapies. Preclinical and limited clinical data
suggest the immune system plays a part in the pathogenesis of the nephropathy,
particularly monocytes/macrophages. In animal models, blocking of CCR2 improves
renal function.
Study objective
The primary efficacy objective of this study is to evaluate the effect of
CCX140-B treatment on urinary albumin excretion in subjects with type 2
diabetes mellitus (T2DM) with albuminuria.
The primary safety objective of this study is to evaluate the safety and
tolerability of CCX140-B in subjects with T2DM with albuminuria.
The secondary objectives of this study are:
1.To evaluate the effect of CCX140-B on hemoglobin A1c (HbA1c);
2.To evaluate the pharmacokinetic (PK) profile of CCX140-B in subjects with
T2DM with albuminuria;
3.To evaluate the effect of CCX140-B on renal function; and
4.To evaluate the effect of CCX140-B on markers of renal function and
inflammation.
Study design
Randomised, double-blind, placebo-controlled intervention
Intervention
10 mg CCX140-B or placebo once daily for 84 consecutive days.
Study burden and risks
The most commonly observed adverse events with CCX140-B were headache, fatigue,
rhinorrhoea, sore throat. These symptoms were temporary. Said side effects are
neither severe nor lasting. The participants contribute to the development of a
novel drug against diabetic nephropathy.
Maude Avenue 850
Mountain View, California 94043
US
Maude Avenue 850
Mountain View, California 94043
US
Listed location countries
Age
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.Albumin:creatinine ratio (ACR) of 100 to 3000 mg/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/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;
4.All subjects must be on a stable dose of an ACE inhibitor or 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. Any oral anti-diabetic treatment must have been maintained at stable dose(s) for at least 8 weeks prior to screening. If receiving insulin, must have been on insulin for at least 8 weeks prior to screening;
5.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;
6.Fasting plasma glucose less than 270 mg/dL at screening;
7.Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
8.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
9.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 prior to the initial dosing.
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 of screening;
7.Use of bardoxolone, atrasentan or other endothelin antagonist within 8 weeks of screening;
8.Received chronic (more than 7 days continuously) NSAID treatment within 2 weeks of screening;
9.Cardiac failure (class III or IV), history of unstable angina, symptomatic coronary artery disease, myocardial infarction or stroke within 12 weeks of 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 <3.5 x 109/L);
13.History or presence of any form of cancer within the 5 years prior to randomization, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis;
14.Presence of tuberculosis based on chest X rays, tuberculin skin test, QuantiFERON®-TB Gold test, or T-SPOT®.TB test performed during screening; If screening test is performed and it is deemed positive due to previous vaccination or TB exposure, chest X rays must be acquired to rule out TB;
15.Positive HBV, HCV, or HIV viral screening test;
16.History of gastrointestinal conditions that may interfere with study medication compliance, e.g., severe gastroparesis, with regurgitation of food or oral medication;
17.History of alcohol or illicit drug abuse;
18.Any infection requiring antibiotic treatment within 4 weeks of screening;
19.Hemoglobin less than 10 g/dL (or 6.18 mmol/L) at screening;
20.Evidence of hepatic disease; AST, ALT, or bilirubin > 2 x the upper limit of normal;
21.Clinically significant abnormal ECG during screening, e.g., QTc greater than 450 msec;
22.Participation in another clinical trial within 3 months prior to the start of this study or more than 4 times per year; 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2011-003049-16-NL |
CCMO | NL37590.058.11 |