Hyperphosphatemia
Conditions
Keywords
Chronic hemodialysis, Investigational drug
Brief summary
This three-part study will be performed with participants on chronic hemodialysis. * Part A will assess plasma pharmacokinetics of DS2330a (free form of DS2330b) after a single dose of powder in bottle (PIB) or tablet formulations of DS2330b * Part B will test the safety, tolerability, and effects on serum phosphate (Pi) of 14-day repeated oral doses of DS-2330b PIB when given alone and when given along with sevelamer carbonate three times a day * Part C is optional, and will test the effects on serum phosphate (Pi) of 14-day repeated oral doses of DS-2330b tablets when given with sevelamer carbonate After screening, participants should expect the study to last about 21 days for Part A, and 46 days for Parts B and C.
Interventions
DRUGDS-2330b PIB
DS-2330b as powder in bottle with stock solution (PIB)
DRUGPlacebo
Placebo matching stock solution in bottle
DRUGSevelamer
Sevelamer is a phosphate binder. It is used to decrease serum phosphate (Pi) level in people with chronic kidney disease who are on dialysis.
DRUGDS-2330b Tablet
DS-2330b as tablet formulation
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Masking description is for Part B only - Parts A and C are Open Label, so have no masking
Intervention model description
Part A has a 2-period, open-label, randomized, 2-way crossover design with a single dose of Treatments A1 and A2 Part B participants are randomized with a 2:3:3:3 ratio to Treatment B1, B2, B3, and B4, respectively, using a double-blind, repeated dose, parallel design Part C is an optional, single-arm, open label, repeated dose design
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Has a body mass index (BMI) of 18 kg/m\^2 to 40 kg/m\^2 (inclusive) * Is on prescribed maintenance hemodialysis (three times a week) for at least 3 months before Screening with adequacy demonstrated by a dialysis clearance within 3 months before the first dose of the investigational medicinal product * Has permanent vascular access \[arteriovenous (A-V) fistula or graft\] * Is willing to comply with protocol-specified methods for family planning * For Parts B and C only: 1. Has protocol-specified acceptable serum Pi levels at Screening and in serum Pi after up to 3 weeks of washout from all Pi binders 2. Has protocol-specified acceptable serum Ca\^2+ level and intact parathyroid hormone (iPTH) level at screening
Exclusion criteria
* Is employed by the clinic or the sponsor * Has family relationship with another study participant * Has any history, current condition, or drug use that per protocol or in the opinion of the investigator might compromise: 1. safety of the participant or their children 2. safety of study staff 3. analysis of study results * For Parts B and C only: 1. Is not able to take sevelamer carbonate 2. Has had partial or total parathyroidectomy within the last six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All Parts: Number of trial participants with treatment-emergent adverse events (TEAEs) | through trial completion (about 15 months) | TEAEs are adverse events (side effects) associated with taking an investigational product, whether or not they were caused by the investigational product. Clinically significant changes in physical exam findings, vital signs, electrocardiograms, clinical lab tests and thyroid function are recorded as TEAEs. |
| Part A, Period 2: Tmax of DS-2330a | Period 2, Pre-dose to 48 hours post-dose | — |
| Part A, Period 1: Area under the drug concentration curve (AUC) for DS-2330a over 24 hours (AUC-24) | Period 1, Pre-dose to 24 hours post-dose | — |
| Part A, Period 2: AUC for DS-2330a for DS-2330a over 24 hours (AUC-24) | Period 2, Pre-dose to 24 hours post-dose | — |
| Part A, Period 1: AUC at the last observable concentration (AUClast) and to infinity (AUCinf) for DS-2330a | Period 1, Pre-dose to 48 hours post-dose | Categories (with the same unit of measure ng\*hr/mL): AUClast, AUCinf |
| Part A, Period 2: AUClast and AUCinf for DS-2330a | Period 2, Pre-dose to 48 hours post-dose | Categories (with the same unit of measure ng\*hr/mL): AUClast, AUCinf |
| Parts B and C: Serum phosphate (Pi) levels before hemodialysis | within 15 days | — |
| Part A, Period 1: Maximum concentration (Cmax) of DS-2330a | Period 1, Pre-dose to 48 hours post-dose | — |
| Part A, Period 2: Cmax of DS-2330a | Period 2, Pre-dose to 48 hours post-dose | — |
| Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a | Period 1, Pre-dose to 48 hours post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts B and C: Tmax of DS-2330a | within 24 hours, Day 1 | — |
| Parts B and C: AUC-24 for DS-2330a | Day 1 | — |
| Parts B and C: AUCinf for DS-2330a | Day 1 | — |
| Parts B and C: Minimum concentration (Ctrough) of DS-2330a | within 11 days | Trough blood levels for DS-2330a will be collected before the morning dose (prior to breakfast) |
| Part B: Dialysis clearance of DS-2330a | on Day 11 | — |
| Parts B and C: Cmax of DS-2330a | within 24 hours on Day 1 | — |
Countries
United States
Outcome results
None listed