Dialysis-dependent patients with hyperphosphatemia MedDRA version: 19.0 Level: LLT Classification code 10020712 Term: Hyperphosphatemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: Nicotinamid 250 mg retard Kapseln
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: NICOTINAMIDE
CAS Number: 98-92-0
Current Sponsor code: M111, nicotinamide MR
Ot
Sponsors
MEDICE Arzneimittel Pütter GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Males or females aged 18 years or older Patients with CKD stage 5 and on a stable haemodialysis regimen, 3 times a week for at least 6 months prior to screening Dialysis sessions must be conducted either on Sunday, Monday (morning, midday/afternoon, evening or overnight) or on Tuesday (morning or midday/afternoon) Dialysis regime must remain constant at least until visit W12 Unmodified phosphate binding therapy with one or two phosphate binders for at least 1 month prior to screening Serum phosphate concentration at screening 1.45 mmol/l (4.5 mg/dl) If the patient is on vitamin D replacement and/or active vitamin D therapy, the dose must have remained stable for at least 1 month prior to screening If the patient takes calcimimetics, the dose must have remained stable for at least 1 month prior to screening 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 315 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 385
Exclusion criteria
Exclusion criteria: Chronic heart failure NYHA III or IV in adequate volume state. Cardiac decompensation, which required hospital admission in the last 6 months Myocardial infarction in the last 3 months Uncontrolled hypertension although receiving 3 or more antihypertensive medications Patient with planned parathyroidectomy in the next year High urgency transplant candidate as defined at Eurotransplant at screening Peptic ulcers in the last 6 months Gastro-intestinal hemorrhage - except anal skin tags - in the last 6 month Patients with dysphagia or swallowing difficulties in the last 6 month Intestinal obstructions / ileus in the last 6 month Patients with impaired intestinal absorption (e.g. impaired intestinal motility, pseudo-obstructions, megacolon, short bowel syndrome, Crohn's or coeliac disease) Active gastroparesis, identifiable from nausea and vomiting Rhabdomyolysis Severely impaired vision (e.g. macular edema, maculopathy, severe nonproliferative retinopathy or proliferative retinopathy) Severe hepatic parenchymal diseases Hypersensitivity to nicotinamide or one of the other ingredients Absolute or severe lactose intolerance Simultaneous participation in another clinical trial within the last 2 months Patients who are legally incapacitated or are institutionalized by court or official order Patient with an inadequate command, or no command of written and spoken national language Failure to use highly-effective contraceptive methods in women of child-bearing age Poorly controlled diabetes (HbA1c > 9%) at screening Platelet count 2.65 mmol/l (10.6 mg/dl) at screening Pathological creatine kinase value may not be = 2 times the normal range (men > 380 U/l, women > 334 U/l) at screening; Elevated transaminases (AST or ALT) more than 3 times the normal level at screening Haemoglobin level 180 mmHg systolic or > 110 mmHg diastolic. Change of dialysis mode planned in the next year Pregnant women or positive pregnancy test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Nicotinamide MR compared to placebo as an add-on therapy to approved individual phosphate binders in the long term reduction of elevated phosphate levels in haemodialysis patients;Secondary Objective: not applicable;Primary end point(s): Serum phosphate concentration;Timepoint(s) of evaluation of this end point: 12 weeks post baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Serum phosphate concentration: end value 24 and 52 weeks post baseline Change from screening serum phosphate levels, end value 12, 24 and 52 weeks post baseline Number of responders/non-responder of all randomized patients belonging to the ITT-population. Patients will be considered as non-responders, if the phosphate value is missing at the specific measurement time point (week 12, 24, and 52) or if the study medication was discontinued before the time point. For the remaining cases, a response is defined according to the following 4 definitions separately for each of the 3 measurement time points at week 12, 24 and 52: 1. serum phosphate concentration = 1.78 mmol/l (5,5 mg/dl) 2. serum phosphate concentration = 1.45 mmol/l (4.5 mg/dl) 3. Individual serum phosphate target range achieved · (1.0 mmol/l (3.1 mg/dl) to 1.45 mmol/l (4.5 mg/dl) in patients with screening phosphate levels < 2.0 mmol/l (6.25 mg/dl) · 1.0 mmol/l (3.1 mg/dl) to 1.78 mmol/l (5.5 mg/dl) in patients with screening phosphate levels = 2.0 mmol/l (6.25 mg/dl 4. Individual serum phosphate concentration improved = 0.2mmol/l (0.6 mg/dl) compared to screening Number of responders applying the definition of responders above but limiting the analyses to patients under study medication at the end of the trial with no missing data at the concerning measurement time point. Serum calcium concentration 12, 24 and 52 weeks post baseline Intact parathormone (iPTH) 12, 24 and 52 weeks post baseline High and low density lipoproteins (HDL, LDL) and triglycerides 12, 24 and 52 weeks post baseline Number of patients receiving rescue therapy due to elevated serum phosphate ;Timepoint(s) of evaluation of this end point: different time points (see secondary end points) | — |
Countries
Austria, Germany, Hungary, Poland
Contacts
Public ContactMedizinische Abteilung
MEDICE Arzneimittel Pütter GmbH & Co. KG
Outcome results
None listed