MedPath

DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis

Phase 1
Completed
Conditions
Hyperphosphatemia
Interventions
Drug: DS-2330b PIB
Drug: Placebo
Drug: DS-2330b Tablet
Registration Number
NCT03305471
Lead Sponsor
Daiichi Sankyo
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part B: DS-2330b PIB + SevelamerDS-2330b PIBParticipants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily \[Treatment B3\]
Part A: DS-2330b Tablet, then PIBDS-2330b PIBOn a non-dialysis day, participants are given a single 250 mg dose of DS-2330b in tablet form \[Treatment A2\] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b PIB \[Treatment A1\] right after breakfast.
Part A: DS-2330b PIB, then TabletDS-2330b PIBOn a non-dialysis day, participants are given a single 250 mg dose of DS-2330b PIB \[Treatment A1\] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b in tablet form \[Treatment A2\] right after breakfast.
Part A: DS-2330b PIB, then TabletDS-2330b TabletOn a non-dialysis day, participants are given a single 250 mg dose of DS-2330b PIB \[Treatment A1\] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b in tablet form \[Treatment A2\] right after breakfast.
Part A: DS-2330b Tablet, then PIBDS-2330b TabletOn a non-dialysis day, participants are given a single 250 mg dose of DS-2330b in tablet form \[Treatment A2\] right after breakfast. At least 3 days will be allowed to let the first dose wash out. Then on a non-dialysis day the participants are given a single 250 mg dose of DS-2330b PIB \[Treatment A1\] right after breakfast.
Part B: PlaceboPlaceboParticipants are given placebo three times daily \[Treatment B1\]
Part B: DS-2330b PIBDS-2330b PIBParticipants are given 400 mg of DS-2330b PIB three times daily \[Treatment B2\]
Part B: Placebo + SevelamerPlaceboParticipants are given placebo along with 1.6 grams of sevelamer three times daily \[Treatment B4\]
Part C: DS-2330b Tablet + SevelamerDS-2330b TabletParticipants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily \[Treatment C\]
Part B: DS-2330b PIB + SevelamerSevelamerParticipants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily \[Treatment B3\]
Part B: Placebo + SevelamerSevelamerParticipants are given placebo along with 1.6 grams of sevelamer three times daily \[Treatment B4\]
Part C: DS-2330b Tablet + SevelamerSevelamerParticipants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily \[Treatment C\]
Primary Outcome Measures
NameTimeMethod
Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330aPeriod 1, Pre-dose to 48 hours post-dose
Part A, Period 2: Tmax of DS-2330aPeriod 2, Pre-dose to 48 hours post-dose
Part A, Period 1: Maximum concentration (Cmax) of DS-2330aPeriod 1, 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
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: Cmax of DS-2330aPeriod 2, Pre-dose to 48 hours post-dose
Parts B and C: Serum phosphate (Pi) levels before hemodialysiswithin 15 days
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-2330aPeriod 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-2330aPeriod 2, Pre-dose to 48 hours post-dose

Categories (with the same unit of measure ng\*hr/mL): AUClast, AUCinf

Secondary Outcome Measures
NameTimeMethod
Parts B and C: Tmax of DS-2330awithin 24 hours, Day 13
Parts B and C: AUCinf for DS-2330aDay 13
Parts B and C: Cmax of DS-2330awithin 24 hours on Day 13
Parts B and C: AUC-24 for DS-2330aDay 13
Parts B and C: Minimum concentration (Ctrough) of DS-2330awithin 11 days

Trough blood levels for DS-2330a will be collected before the morning dose (prior to breakfast)

Part B: Dialysis clearance of DS-2330aon Day 11

Trial Locations

Locations (3)

Orlando Clinical Research Center

🇺🇸

Orlando, Florida, United States

DaVita Clinical Research

🇺🇸

Minneapolis, Minnesota, United States

Prism Clinical Research

🇺🇸

Saint Paul, Minnesota, United States

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