DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperphosphatemia
• Intervention / Treatment: Drug: DS-2330b PIB; Drug: DS-2330b Tablet; Drug: Placebo; Drug: Sevelamer

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; DS-2330b as powder in bottle with stock solution (PIB); Drug: DS-2330b Tablet; DS-2330b as tablet formulation
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; DS-2330b as powder in bottle with stock solution (PIB); Drug: DS-2330b Tablet; DS-2330b as tablet formulation
Placebo Comparator: Part B: Placebo; Participants are given placebo three times daily [Treatment B1]	Drug: Placebo; Placebo matching stock solution in bottle
Experimental: Part B: DS-2330b PIB; Participants are given 400 mg of DS-2330b PIB three times daily [Treatment B2]	Drug: DS-2330b PIB; DS-2330b as powder in bottle with stock solution (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; DS-2330b as powder in bottle with stock solution (PIB); Drug: Sevelamer; Sevelamer is a phosphate binder. It is used to decrease serum phosphate (Pi) level in people with chronic kidney disease who are on dialysis.; Other Names: Sevelamer carbonate
Experimental: Part B: Placebo + Sevelamer; Participants are given placebo along with 1.6 grams of sevelamer three times daily [Treatment B4]	Drug: Placebo; Placebo matching stock solution in bottle; Drug: Sevelamer; Sevelamer is a phosphate binder. It is used to decrease serum phosphate (Pi) level in people with chronic kidney disease who are on dialysis.; Other Names: Sevelamer carbonate
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: DS-2330b Tablet; DS-2330b as tablet formulation; Drug: Sevelamer; Sevelamer is a phosphate binder. It is used to decrease serum phosphate (Pi) level in people with chronic kidney disease who are on dialysis.; Other Names: Sevelamer carbonate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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	Categories (with the same unit of measure ng*hr/mL): AUClast, AUCinf	Period 1, Pre-dose to 48 hours post-dose
Part A, Period 2: AUClast and AUCinf for DS-2330a	Categories (with the same unit of measure ng*hr/mL): AUClast, AUCinf	Period 2, Pre-dose to 48 hours post-dose
Parts B and C: Serum phosphate (Pi) levels before hemodialysis		within 15 days
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.	through trial completion (about 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts B and C: Cmax of DS-2330a		within 24 hours on Day 1
Parts B and C: Cmax of DS-2330a		within 24 hours on Day 13
Parts B and C: Tmax of DS-2330a		within 24 hours, Day 1
Parts B and C: Tmax of DS-2330a		within 24 hours, Day 13
Parts B and C: AUC-24 for DS-2330a		Day 1
Parts B and C: AUC-24 for DS-2330a		Day 13
Parts B and C: AUCinf for DS-2330a		Day 1
Parts B and C: AUCinf for DS-2330a		Day 13
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)	within 11 days
Part B: Dialysis clearance of DS-2330a		on Day 11

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2017
• Primary Completion (Actual): January 3, 2019
• Study Completion (Actual): January 3, 2019

Study Registration Dates

• First Submitted: October 4, 2017
• First Submitted That Met QC Criteria: October 9, 2017
• First Posted (Actual): October 10, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Chronic hemodialysis; Investigational drug
• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperphosphatemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: DS2330-A-U103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No