Patients with chronic kidney disease stage 5D (CKD-5D) and evidence of mineral and bone disorder as judged by low serum intact PTH levels according to KDIGO guidelines
Conditions
Interventions
Product Code: BPS804
Pharmaceutical Form: Powder for solution for infusion
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Written informed consent must be obtained before any assessment is performed. •Males and females aged 18 to 80 years included, with CKD-5D (GFR 3 months before screening with a stable dialysis prescription, as defined by no change in material (i.e., dialyzer, filter/ membrane) type and dialysis duration for = 4 weeks before screening. • 2 evaluable consecutive vertebral bodies for DXA (no fractures, no sclerosis). • Pre-dialysis serum calcium, adjusted for serum albumin, =2.55 mmol/L and pre-dialysis serum phosphate =1.8 mmol/L for = 80% of samples over 2 months prior to screening. • Low BMD, defined as a T-score for the lumbar spine or femoral neck or total hip between -1.0 and =- 4.0 as determined by DXA at time of screening. • If patient is currently being treated with calcimimetics, prescribed dose must be constant for at least 30 days prior to screening • If patient is currently being treated with vitamin D, the prescribed dose must be constant for at least 30 days prior to screening •Screening body mass index (BMI) between >18.5 and = 35 kg/m2 and weigh of at least 50 kg. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients who are on peritoneal dialysis. • Patients who had a parathyroidectomy within 3 months prior to screening or patients who have a parathyroidectomy scheduled during the course of the study. • Patients who have a kidney transplant scheduled during the study. • Patients who have an increased baseline risk of osteosarcoma: Paget's disease of the bone or unexplained and clinically significant elevations of alkaline phosphatase and/or patients who have received radiation therapy involving the skeleton. • Patients with clinically symptomatic spinal stenosis. • Patients with a history of an osteoporotic fracture (e.g., low trauma, fragility fracture of vertebrae, wrist, radius, humerus, or hip). • Women who are pregnant or nursing (lactating). • Women of child-bearing potential who are planning a pregnancy during the course and duration of the study. • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and for 5 half-lives (i.e., around 10 weeks) after stopping treatment. Highly effective contraception is defined as either: a. Total abstinence: When this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]. b. Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. c. Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female study patients, the vasectomised male partner should be the sole partner for that patient]. d. Use of a combination of any two of the following (1+2 or 1+3 or 2+3): 1) Use of oral, injected or implanted hormonal methods of contraception. 2) Placement of an intrauterine device (IUD) or intrauterine system (IUS). 3) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. • Liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), ?-GT. • Hemoglobin of = 9 g/dL in male, and = 8 g/dL in female patients. (Note: Treatment with erythropoietin-stimulating agents (ESA) is allowed). • Patients who are regularly using or have regularly used agents affecting bone metabolism
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary objective of the study is to evaluate the safety and tolerability of BPS804 when administered as a single i.v. infusion in patients with late stage CKD (stage 5D). Adverse events will be counted within each treatment and study part, corresponding percentages will be tabulated. Data from patients receiving placebo will be pooled within each part of the study. The numbers and percentages will be tabulated by body system, preferred term, and severity. Safety analysis of other safety assessments will be carried out descriptively. ;Main Objective: The primary objective is to assess the safety and tolerability following administration of a single dose of BPS804 in patients with CKD-5D.;Secondary Objective: To determine the pharmacokinetic (PK) profile of BPS804 in serum and dialysate. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of this trial is to determine the PK profile of BPS804 in serum and dialysate. Concentrations of BPS804 will be measured at predose, 2 hrs, 24 hrs, 44 hrs (pre-dialysis), 48 hrs (post-dialysis PK samples and dialysate), 168 hrs, and 15, 22, 29, 57, and 85 days following administration of BPS804. The following pharmacokinetic parameters will be determined using non compartmental methods for AUClast, AUCinf, Cmax, Tmax, and T1/2 to evaluate concentration of BPS804. | — |
Countries
United Kingdom
Contacts
Public ContactMedical Information Services
Novartis Pharmaceuticals UK Limited
Outcome results
None listed