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 effects of multiple oral doses of
MT-3995 on albuminuria as assessed by the urine
albumin-to-creatinine ratio (UACR).
To evaluate the safety and tolerability of multiple oral
doses of MT-3995 in subjects with Type II diabetic
nephropathy with albuminuria. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
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) |
Primary 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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |