Type II Diabetes Mellitus with nephropathy and Albuminuria' MedDRA version: 17.0 Level: PT Classification code 10061835 Term: Diabetic nephropathy System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
Mitsubishi Tanabe Pharma Corporation (MTPC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.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.(WHO/NMH/CHP/CPM/11.1). 2. 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 predose). 3. Glycosylated haemoglobin (HbA1c) =10.5% at screening and Week -2. 4. An eGFR(MDRD formula20) =30-50 years old as =1 year since their last menstrual period. If there are doubts as to the woman's menopausal status, the levels of follicle stimulating hormone may be monitored. Women practicing abstinence or where the partner is sterile should be considered to be of childbearing potential. 11. Male participants in the study should use one of the following methods of contraception while having sexual intercourse with WOCBP from screening until at least 120 days after the last dosing day: total abstinence, condom (male or female) with spermicide. 12. Subjects who are capable of giving informed consent, complying with the restrictions and requirements of the protocol and, in the opinion of the Investigator, will be able to complete the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 28 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: -1. History of Type I diabetes, pancreas or ß-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy. 2. Central laboratory serum potassium level 5.2 mmol/L at screening, Week -2 or baseline (Day 1 pre-dose). 3. Local laboratory serum potassium level 5.2 mmol/L at baseline (Day 1 pre-dose). 4. Evidence of active urinary tract infection at screening. 5. Subjects who had acute kidney injury (AKI) within 3 months prior to baseline (Day 1 pre dose) or have undergone renal dialysis at any time prior to randomisation. 6. Subjects with a history of renal transplant. 7. Subjects diagnosed with non-diabetic kidney disease significantly impacting on albuminuria. 8. Subjects who are on both ARB and ACE-I. XML File Identifier: Dj9dIaFdGVyD2UXRfP8TdwvNOO4= Page 19/32 9. Subjects with a persistent DBP 20 mmHg decrease in SBP and/or >10 mmHg decrease in DBP associated with clinical manifestations at screening. 11. =3 × upper limit of normal (ULN) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening or Week -2. 12. Clinically significant abnormalities of the thyroid (hypo- or hyperthyroidism measured by TSH, FT3 and FT4) at screening or Week - 2, or subjects on thyroxine replacement therapy. 13. Subjects with evidence of acute ischaemia on 12-lead ECG at screening or baseline (Day 1 pre-dose). 14. Presence, history or known family history of long QT syndrome or Torsades de Pointes. 15. History of clinically significant multiple or severe drug allergies, allergy to MT-3995 or to any excipients (mannitol, carmellose calcium, light anhydrous silicic acid, talc and magnesium stearate) in the MT- 3995 and matching placebo capsule. 16. Excessive consumption of food or drink containing high levels of potassium such as orange juice, melon and bananas, defined by local practice. 17. History of hospitalisation for hyperkalemia or AKI induced by previous RAAS blocker treatment. 18. Subjects who are taking any of the prohibited drugs, supplements or herbal remedies at screening or baseline (Day 1 pre-dose) (see Section 6.3.2). Any other medications will be allowed to continue unless in the opinion of the Sponsor and the Investigator, the medication will interfere with the objective of the study or compromise the subject's safety. 19. Subjects who had general laser eye surgery 3 months prior to baseline (Day 1 pre-dose) or plan general laser eye surgery during the time the subject is expected to participate in the study. 20. Stroke, acute limb ischaemia, coronary and peripheral revascularisation procedure or myocardial infarction in the 6 months prior to baseline (Day 1 pre-dose). 21. Subjects with heart failure New York Heart Association Class III-IV at screening. 22. Body mass index (BMI) >45 kg/m2 at screening. 23. Subjects who are suffering from any disease which, in the opinion of the Investigator, is sufficiently severe to render the subject unfit, or affect the subject's ability to participate in the study. Subjects with evidence of any malignancy within the last 5 years prior to screening, with the exception of history of basal cell skin cancer. 24. Subjects who participated in a clinical study of any IMP (other tha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To evaluate the safety and tolerability of multiple oral doses of MT-3995 in subjects with Type II diabetic nephropathy with albuminuria.;Secondary Objective: -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.;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.;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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;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 | — |
Countries
Bulgaria, Czech Republic, Hungary, Poland, Slovakia
Contacts
Public ContactRA Manager
Mitsubishi Pharma Europe Ltd (MPE)
Outcome results
None listed