Clinical trial NCT03305471: DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis
Official title: A Phase 1b Study, to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Repeated Doses of DS-2330b Alone and When Co-administered With Sevelamer in Patients on Chronic Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperphosphatemia
Keywords: Chronic hemodialysis
Investigational drug
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2017-10-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A, Period 1: Maximum concentration (Cmax) of DS-2330a
timeFrame: Period 1, Pre-dose to 48 hours post-dose
measure: Part A, Period 2: Cmax of DS-2330a
timeFrame: Period 2, Pre-dose to 48 hours post-dose
measure: Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a
timeFrame: Period 1, Pre-dose to 48 hours post-dose
measure: Part A, Period 2: Tmax of DS-2330a
timeFrame: Period 2, Pre-dose to 48 hours post-dose
measure: Part A, Period 1: Area under the drug concentration curve (AUC) for DS-2330a over 24 hours (AUC-24)
timeFrame: Period 1, Pre-dose to 24 hours post-dose
measure: Part A, Period 2: AUC for DS-2330a for DS-2330a over 24 hours (AUC-24)
timeFrame: Period 2, Pre-dose to 24 hours post-dose
measure: Part A, Period 1: AUC at the last observable concentration (AUClast) and to infinity (AUCinf) for DS-2330a
timeFrame: Period 1, Pre-dose to 48 hours post-dose
measure: Part A, Period 2: AUClast and AUCinf for DS-2330a
timeFrame: Period 2, Pre-dose to 48 hours post-dose
measure: Parts B and C: Serum phosphate (Pi) levels before hemodialysis
timeFrame: within 15 days
measure: All Parts: Number of trial participants with treatment-emergent adverse events (TEAEs)
timeFrame: through trial completion (about 15 months)
Secondary outcomes:
measure: Parts B and C: Cmax of DS-2330a
timeFrame: within 24 hours on Day 1
measure: Parts B and C: Cmax of DS-2330a
timeFrame: within 24 hours on Day 13
measure: Parts B and C: Tmax of DS-2330a
timeFrame: within 24 hours, Day 1
measure: Parts B and C: Tmax of DS-2330a
timeFrame: within 24 hours, Day 13
measure: Parts B and C: AUC-24 for DS-2330a
timeFrame: Day 1
measure: Parts B and C: AUC-24 for DS-2330a
timeFrame: Day 13
measure: Parts B and C: AUCinf for DS-2330a
timeFrame: Day 1
measure: Parts B and C: AUCinf for DS-2330a
timeFrame: Day 13
measure: Parts B and C: Minimum concentration (Ctrough) of DS-2330a
timeFrame: within 11 days
measure: Part B: Dialysis clearance of DS-2330a
timeFrame: on Day 11
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: DaVita Clinical Research
state: Colorado
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
city: Saint Paul
country: United States
facility: Prism Clinical Research
state: Minnesota
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: