E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Progressive kidney disease caused by diabetes |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
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 |
|
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 compare the effect of nidufexor to placebo on albuminuria in patients with diabetic nephropathy already receiving treatment with ACEI or ARB
-To assess the safety and tolerability of nidufexor |
|
E.2.2 | Secondary objectives of the trial |
- To determine the effect of nidufexor on
renal filtration function
- To assess the pharmacokinetic properties of nidufexor at steady state in patients with type 2 diabetes and nephropathy
- To determine the effect of nidufexor on renal tubular function
- To determine the effect of nidufexor on anthropometric assessments
- To determine the effect of nidufexor on lipids |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male/female patients, 18-75 years
• Written informed consent
• Diagnosis of Type 2 diabetes mellitus, with
diagnosis made at least 6 months prior to screening
• Diabetic nephropathy as evidenced by Urine
albumin-Cr ratio (UACR) ≥300 mg/g Cr while
receiving a maximally tolerated (optimal) dose of
angiotensin converting enzyme inhibitor or
angiotensin receptor blocker |
|
E.4 | Principal exclusion criteria |
• History of type 1 diabetes mellitus
• Severe renal impairment manifesting as serum creatinine eGFR < 30 mL/min/1.73 m^2 at screening
• Pregnant or nursing (lactating) women
• Women of child-bearing potential, unless allowed by local regulations and they are using highly effective methods of contraception during dosing and for 5 days after stopping study medication
• Uncontrolled diabetes mellitus
• History or current diagnosis of ECG abnormalities
• History of kidney disease other than diabetic nephropathy |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Effect of nidufexor to placebo on albuminuria in patients with
diabetic nephropathy by estimating Urine albumin-creatinine ratio (UACR) at serial time points and 24-hour urinary albumin at baseline and end of study.
Safety and tolerability assessments using safety endpoints: vital signs, physical examination, laboratory measurements, ECG parameters, adverse events |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
day 1, 14, 29, 57, 85, 113, 141, 169 and day 197 |
|
E.5.2 | Secondary end point(s) |
effect of nidufexor on renal filtration function utilizing Estimated glomerular filtration rate
Cmax of nidufexor at steady state in patients with type 2 diabetes and nephropathy
Tmax of nidufexor at steady state in patients with type 2 diabetes and nephropathy
AUClast of nidufexor at steady state in patients with type 2 diabetes and nephropathy
effect of nidufexor on renal tubular function utilizing Free
water clearance
effect of nidufexor on anthropometric assessments (weight, height, and waist-to hip ratio)
effect of nidufexor on lipids utilizing Fasting lipid profile,
including lipoprotein (a) [Lp (a)] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 1, 14, 29, 57, 85, 113, 141 and day 169 |
|
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Czechia |
Germany |
Jordan |
Lebanon |
Turkey |
United States |
|
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |