E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus with Nephropathy and Albuminuria |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061835 |
E.1.2 | Term | Diabetic nephropathy |
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 evaluate the safety and tolerability of multiple oral
doses of MT-3995 in subjects with Type II diabetic
nephropathy with albuminuria. |
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E.2.2 | Secondary objectives of the trial |
*To evaluate the effects of multiple oral doses of MT 3995 on albuminuria as assessed by the urine albumin-to-creatinine ratio (UACR).
*To determine plasma concentrations of MT-3995 and its
major metabolite (chlorinated metabolite: 1118174) after
multiple oral doses of MT-3995 in subjects with Type II
diabetic nephropathy with albuminuria.
*To determine the change from baseline in sitting Systolic
Blood Pressure (SBP) and Diastolic Blood Pressure
(DBP) in subjects with Type II diabetic nephropathy
with albuminuria. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and female subjects aged 18 to 75 years who have been diagnosed with Type II diabetes mellitus according to the criteria of the WHO.
-Subjects with a clinical diagnosis of diabetic nephropathy, who have been treated with ACE-I or ARB for a minimum of 12 weeks prior to screening and have been receiving a stable dose for at least 4 weeks prior to screening and remain on a stable dose up to baseline (Day 1 pre-dose).
-Subjects with stable BP at Week -2 (compared with Week -4) and at baseline, Day 1 pre-dose (compared with Week -2). Stable BP is defined as a DBP within ± 10 mmHg from the previous BP measurement. Subjects must also have a DBP <110 mmHg and an SBP <180 mmHg at Week -4, Week -2 and baseline (Day 1 pre-dose).
-Albuminuria (UACR) ≥50 mg/g and ≤3500 mg/g (i.e., ≥5.66 mg/mmol and ≤395.85 mg/mmol) measured by median values of first-morning void urine samples on three consecutive days, both at screening and Week -2.
-An estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD] formula) ≥60 mL/min/1.73m2 at screening and Week -2. Due to variability, subjects with an eGFR of 57-59 mL/min/1.73m2 may be enrolled in the study at the discretion of the Investigator. |
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E.4 | Principal exclusion criteria |
-Central laboratory serum potassium level <3.5 or >5.2 mmol/L at screening, Week -2 or baseline (Day 1 pre-dose).
-Local laboratory serum potassium level <3.5 or >5.2 mmol/L at baseline (Day 1 pre-dose).
-Clinically significant abnormalities of the thyroid (hypo- or hyperthyroidism measured by thyroid stimulating hormone, free triiodothyronine and free thyroxine) at screening or Week -2, or subjects on thyroxine replacement therapy.
-Subjects who are on both ARB and ACE-I.
-History of hospitalisation for hyperkalemia or acute kidney injury induced by previous renin-angiotensin-aldosterone system blocker treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoint:
-Within-group comparison of percentage change in first-morning UACR from baseline (median of three values on consecutive days prior to Day 1) to Week 8. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the study - please refer to the detailed Time and Events Schedule in the protocol for full details |
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E.5.2 | Secondary end point(s) |
-Percentage change in first-morning UACR from baseline (median of three values on consecutive days prior to Day 1) to Week 8 compared to placebo.
-Change from baseline (Day 1 pre-dose) in sitting SBP/DBP to Weeks 1, 2, 4, 6 and 8 within group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the study - please refer to the detailed Time and Events Schedule in the protocol for full details |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 3 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
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 | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |