Clinical trial NCT01372124: A Phase I Clinical Trial to Evaluate the Effect of Renal Impairment on Pharmacokinetics of NOX-E36
Official title: A Phase I, Open Label, Parallel Group, Multi-center Single Dose Trial to Evaluate the Effect of Renal Impairment on Pharmacokinetics of NOX-E36
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal impairment
NOX-E36
Lead sponsor: TME Pharma AG
Sponsor class: INDUSTRY
First posted: 2011-06-13
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi center, open label, parallel group, single administration, phase I trial, in subjects with mild, moderate or severe renal impairment and a control group with normal renal function.

Detailed description: Current diabetes therapy does not stop progression of the disease and the development of diabetes mellitus (DM)-associated complications. A major concern in DM-patients is renal impairment due to nephropathy leading to a reduced glomerular filtration rate (GFR). It has been established that chronic (sub)clinical inflammation is crucial for the onset and progression of DM.

CCL2, also known as Monocyte chemoattractant protein 1 (MCP 1) is a chemokine from the cysteine-cysteine family, secreted by leukocytes or tissue cells. CCL2 promotes monocyte emigration from the bone marrow, activates monocytes and macrophages and directs their migration to sites of inflammation. Recent animal studies and clinical trials indicate a critical involvement of CCL2 in DM and diabetic nephropathy, suggesting that CCL2 may be a potential target for therapeutic intervention in DM. Finally, protein overload and oxidative challenge of the diseased kidney was suggested to stimulate CCL2 expression in renal tubuli, thereby accelerating the progression of diabetic nephropathy.

As NOX E36 is designed to specifically target human MCP-1/CCL2. This study is performed to evaluate the role of renal impairment for adequate dosing recommendations in the planned target population.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects (age 18-75 years, both inclusive)
2. Male subjects who agree to sexual abstinence and/or use a highly effective method of birth control. Female partners of male subjects must be of non-child bearing potential or must practice an adequate non-hormonal contraceptive method to prevent pregnancies.
3. Subjects will be categorized as follows based on creatinine clearance(mL/min/1.73m2): Normal renal function: CrCl \> 80; mild renal impairment: 50 ≤ CrCl ≤ 80; moderate renal impairment: 30 ≤ CrCl ≤ 50; severe renal impairment: CrCl \< 30
4. Body Mass Index (BMI) between 22 and 40 kg/m², both inclusive.

Exclusion Criteria:

1. Women of childbearing potential
2. Patients who have received kidney transplantation.
3. Patients receiving hemodialysis to control their disease.
4. Any clinically significant abnormality other than related to the renal impairment following the investigator's review of the physical examination, ECG and clinical laboratory tests at screening.
5. Not able to communicate meaningfully with the investigator and staff.

Primary outcomes:
measure: Pharmacokinetics
Secondary outcomes:
Other outcomes:
Locations:
city: Balatonfüred
country: Hungary
facility: DRC
city: Chisinau
country: Moldova, Republic of
facility: Innophar Mo S.R.L.
Study officials:
affiliation: INNOPHAR MO s.R.L.
name: Boris Sazu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: DRC
name: Éva Péterfai
role: PRINCIPAL_INVESTIGATOR
References: