NOX-E36 Multiple Ascending Dose Study in Healthy Volunteers and Patients With Type 2 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
The primary objective of this trial is to evaluate the safety and tolerability of multiple intravenous doses of NOX-E36 in healthy subjects and patients with type 2 diabetes mellitus. A secondary objective of the trial is to obtain exploratory estimates of the pharmacodynamic response at the level of inflammation, metabolism as well as ongoing diabetes complications (e.g. impaired cardiovascular, liver and renal function). Thus, the study is designed to provide sufficient safety and dose-response data for a planned Phase IIa proof of concept study with NOX-E36 in patients with multiple complications of type II diabetes mellitus.

Official Title
-----------------
NOX-E36 - A Phase Ib, Multiple Intravenous Dose Study to Evaluate Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties in Healthy Subjects and Then in Three Groups of Patients With Type 2 Diabetes Mellitus to Compare Three Ascending Dose Regimens in a Double-blind and Placebo-controlled Manner

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: NOX-E36
* Drug: NOX-E36


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Group A: Healthy male and female subjects Group B-D: Patients with type 2 diabetes mellitus according to ADA definition; GFR > 60 mL/min; HbA1c ≥ 6.0 and ≤9.0 %; normoalbuminuria, microalbuminuria or macroalbuminuria Exclusion Criteria: History of or presence of clinically significant diseases with the exception of diabetes (Groups B-D) Concurrent illness that may affect blood glucose other than diabetes Supine blood pressure at screening, after resting for 5 min, of >140 mmHg systolic or > 90 mmHg diastolic (Group A) or > 160 mmHg systolic or > 95 mmHg in diabetes mellitus patients (Groups B-D) Clinically significant abnormal ECG at screening Any kidney disease not caused by diabetes or hypertension Type 1 diabetes mellitus

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Drug: NOX-E36<br>* Multiple dose 0.25 mg/kg or placebo i.v. to healthy volunteers; dosing frequency q2d<br>|
| Experimental: Group B - D<br> | Drug: NOX-E36<br>* Multiple dose of 0.0625 mg/kg, 0.125 mg/kg, 0.25 mg/kg or placebo i.v. to patients with type 2 diabetes mellitus (ratio 3:1); dosing frequency q2d<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of multiple intravenous doses of NOX-E36 in healthy subjects and patients with type II diabetes mellitus |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple dose pharmacokinetics and pharmacodynamics of NOX-E36 in healthy subjects and patients with type II diabetes mellitus |  | 4 weeks |