E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diabetes mellitus type II and albuminuria |
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E.1.1.1 | Medical condition in easily understood language |
diabetes mellitus type II and albuminuria |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001580 |
E.1.2 | Term | Albuminuria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the effects of 12 weeks treatment with study drug on albumin-creatinine ratio (ACR) in patients with type 2 diabetes and albuminuria |
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E.2.2 | Secondary objectives of the trial |
• To characterize the effect of study drug on glycosylated hemoglobin fraction (HbA1c)
• To evaluate the effect of study drug on markers of glycemic disorders, systemic inflammation, renal and liver disease and cardiovascular function
• To assess the safety and tolerability of study drug
• To determine the population pharmacokinetics (PK) of study drug |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Type 2 diabetes mellitus according to American Diabetes Association (ADA) definition
2) Age ≥ 18
3) HbA1c between 6.0% and 10.5%, inclusive
4) ACR > 100 mg/g calculated 3 times in first morning void urine, at least 2 of the measurements > 100 mg/g
5) Patients on stable (unchanged medication for at least 3 months) treatment to control hypertension, hyperglycemia and (if applicable) dyslipidemia
6) Stable treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin II receptor blockers (ARBs) (renin-angiotensin system [RAS] blockade)
7) Willing and able to understand and sign an approved Informed Consent form
8) Men must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment. Women must be of non-childbearing potential |
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E.4 | Principal exclusion criteria |
1) Type 1 diabetes mellitus
2) eGFR ≤25 mL/min/1.73m2 (calculated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
3) Recent cardiovascular events (3 months)
4) Uncontrolled hypertension (upper limits 180/110 mmHg)
5) Dialysis and/or acute kidney injury within 3 months before screening
6) Significant edema, infectious diseases, leg ulcers
7) Severe concurrent disease which, in the judgment of the investigator, would interfere significantly with the assessments of safety and efficacy during this study
8) Treatment with any other investigational agent, or participation in another clinical study within 90 days prior to baseline visit
9) Patient with known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
10) In the judgment of the clinical investigator, clinically significant abnormal laboratory values at the screening visit
11) Use of thiazolidinedione class drugs, immune suppressants, steroid therapy (except for topical use or inhalation), chronic use of non-steroidal anti-inflammatory drug (NSAIDs), cyclooxygenase type 2 (COX-2) inhibitors, two or more diuretic drugs and/or aliskiren
12) In the judgment of the clinical investigator, patients who are likely to be non- compliant or uncooperative during the study
13) Previous participation (randomization) in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter is the effect of study drug and placebo on the change in ACR (week 12, minues baseline). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Days -30 to -1, 1, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169
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E.5.2 | Secondary end point(s) |
- ACR calculated in first morning void urine
- HbA1c and hsCRP in serum
- Homeostasis Model of Insulin Resistance (HOMA–IR)
- Flow cytometric determination of CCR2 positive leukocyte subsets in peripheral blood
- Changes in blood pressure as marker of cardiovascular function
- Further urine and serum/plasma markers of glycemic disorders, systemic inflammation, renal and liver disease and cardiovascular function |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-ACR: Days -30 to -1, 1, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169
-hsCRP and HbA1c: Days -30 to -1, 1, 29, 57, 85, 113
-HOMA-IR: Days 1, 85, 113
- Further urine and serum/plasma markers of glycemic disorders, systemic inflammation, renal and liver disease and cardiovascular function: Days 1, 29, 57, 85, 113
- Changes in blood pressure:Days -30 to -1, 1, 29, 57, 85, 113 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |