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CompletedNCT03305471Updated Mar 25, 2019

DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis

A Phase 1 interventional study of DS-2330b PIB and Placebo in Hyperphosphatemia, sponsored by Daiichi Sankyo. Completed at 4 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2019-03-25.

Sponsored by Daiichi Sankyo · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Hyperphosphatemia

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Keywords

  • Chronic hemodialysis
  • Investigational drug
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Part A: DS-2330b PIB, then Tablet

    On 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.

    Drug: DS-2330b PIB · Drug: DS-2330b Tablet

  • Experimental
    Part A: DS-2330b Tablet, then PIB

    On 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.

    Drug: DS-2330b PIB · Drug: DS-2330b Tablet

  • Placebo comparator
    Part B: Placebo

    Participants are given placebo three times daily \[Treatment B1\]

    Drug: Placebo

  • Experimental
    Part B: DS-2330b PIB

    Participants are given 400 mg of DS-2330b PIB three times daily \[Treatment B2\]

    Drug: DS-2330b PIB

  • Experimental
    Part B: DS-2330b PIB + Sevelamer

    Participants are given 400 mg of DS-2330b PIB along with 1.6 grams of sevelamer three times daily \[Treatment B3\]

    Drug: DS-2330b PIB · Drug: Sevelamer

  • Experimental
    Part B: Placebo + Sevelamer

    Participants are given placebo along with 1.6 grams of sevelamer three times daily \[Treatment B4\]

    Drug: Placebo · Drug: Sevelamer

  • Experimental
    Part C: DS-2330b Tablet + Sevelamer

    Participants are given one 250 mg dose of DS-2330b in tablet form along with 1.6 grams of sevelamer three times daily \[Treatment C\]

    Drug: Sevelamer · Drug: DS-2330b Tablet

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.

    Also known as: Sevelamer carbonate

  • DrugDS-2330b Tablet

    DS-2330b as tablet formulation

05

What researchers measure

Primary outcomes

  1. Part A, Period 1: Maximum concentration (Cmax) of DS-2330a

    Time frame: Period 1, Pre-dose to 48 hours post-dose

  2. Part A, Period 2: Cmax of DS-2330a

    Time frame: Period 2, Pre-dose to 48 hours post-dose

  3. Part A, Period 1: Time to maximum concentration (Tmax) of DS-2330a

    Time frame: Period 1, Pre-dose to 48 hours post-dose

  4. Part A, Period 2: Tmax of DS-2330a

    Time frame: Period 2, Pre-dose to 48 hours post-dose

  5. Part A, Period 1: Area under the drug concentration curve (AUC) for DS-2330a over 24 hours (AUC-24)

    Time frame: Period 1, Pre-dose to 24 hours post-dose

  6. Part A, Period 2: AUC for DS-2330a for DS-2330a over 24 hours (AUC-24)

    Time frame: Period 2, Pre-dose to 24 hours post-dose

  7. Part A, Period 1: AUC at the last observable concentration (AUClast) and to infinity (AUCinf) for DS-2330a

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

    Time frame: Period 1, Pre-dose to 48 hours post-dose

  8. Part A, Period 2: AUClast and AUCinf for DS-2330a

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

    Time frame: Period 2, Pre-dose to 48 hours post-dose

  9. Parts B and C: Serum phosphate (Pi) levels before hemodialysis

    Time frame: within 15 days

  10. All Parts: Number of trial participants with treatment-emergent adverse events (TEAEs)

    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.

    Time frame: through trial completion (about 15 months)

Secondary outcomes

  1. Parts B and C: Cmax of DS-2330a

    Time frame: within 24 hours on Day 1

  2. Parts B and C: Cmax of DS-2330a

    Time frame: within 24 hours on Day 13

  3. Parts B and C: Tmax of DS-2330a

    Time frame: within 24 hours, Day 1

  4. Parts B and C: Tmax of DS-2330a

    Time frame: within 24 hours, Day 13

  5. Parts B and C: AUC-24 for DS-2330a

    Time frame: Day 1

  6. Parts B and C: AUC-24 for DS-2330a

    Time frame: Day 13

  7. Parts B and C: AUCinf for DS-2330a

    Time frame: Day 1

  8. Parts B and C: AUCinf for DS-2330a

    Time frame: Day 13

  9. Parts B and C: Minimum concentration (Ctrough) of DS-2330a

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

    Time frame: within 11 days

  10. Part B: Dialysis clearance of DS-2330a

    Time frame: on Day 11

06

Study locations

4 sites
  • DaVita Clinical Research
    Lakewood, Colorado 80228, United States
  • Orlando Clinical Research Center
    Orlando, Florida 32809, United States
  • DaVita Clinical Research
    Minneapolis, Minnesota 55404, United States
  • Prism Clinical Research
    Saint Paul, Minnesota 55114, United States
07

Registry details

Key details

Study ID
NCT03305471
Lead sponsor
Daiichi Sankyo
Responsible party
Sponsor
First posted
Oct 10, 2017
Start date
Aug 17, 2017
Primary completion
Jan 3, 2019
Completion
Jan 3, 2019
Last update
Mar 25, 2019

Study contacts

Global Clinical Leader
study director · Daiichi Sankyo

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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