DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis

NCT03305471 | Completed Phase 1 FDA Drug

• 1 other identifier: DS2330-A-U103
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

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.

Conditions

Hyperphosphatemia

Keywords

Chronic hemodialysis; Investigational drug

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (10)

• 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

Study Arms (7)

Part A: DS-2330b PIB, then Tablet

EXPERIMENTAL

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

Part A: DS-2330b Tablet, then PIB

EXPERIMENTAL

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

Part B: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Part B: DS-2330b PIB

EXPERIMENTAL

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

Drug: DS-2330b PIB

Part B: DS-2330b PIB + Sevelamer

EXPERIMENTAL

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

Part B: Placebo + Sevelamer

EXPERIMENTAL

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

Drug: Placebo; Drug: Sevelamer

Part C: DS-2330b Tablet + Sevelamer

EXPERIMENTAL

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

DS-2330b PIB DRUG

DS-2330b as powder in bottle with stock solution (PIB)

Part A: DS-2330b PIB, then Tablet; Part A: DS-2330b Tablet, then PIB; Part B: DS-2330b PIB; Part B: DS-2330b PIB + Sevelamer

Placebo DRUG

Placebo matching stock solution in bottle

Part B: Placebo; Part B: Placebo + Sevelamer

Sevelamer DRUG

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

Part B: DS-2330b PIB + Sevelamer; Part B: Placebo + Sevelamer; Part C: DS-2330b Tablet + Sevelamer

DS-2330b Tablet DRUG

DS-2330b as tablet formulation

Part A: DS-2330b PIB, then Tablet; Part A: DS-2330b Tablet, then PIB; Part C: DS-2330b Tablet + Sevelamer

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Has protocol-specified acceptable serum Pi levels at Screening and in serum Pi after up to 3 weeks of washout from all Pi binders
• Has protocol-specified acceptable serum Ca\^2+ level and intact parathyroid hormone (iPTH) level at screening

You may not qualify if:

• 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:
• safety of the participant or their children
• safety of study staff
• analysis of study results
• For Parts B and C only:
• Is not able to take sevelamer carbonate
• Has had partial or total parathyroidectomy within the last six months

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (4)

DaVita Clinical Research

Lakewood, Colorado, 80228, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Prism Clinical Research

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.

  PMID: 40576086 DERIVED

MeSH Terms

Conditions

Hyperphosphatemia

Interventions

Sevelamer

Condition Hierarchy (Ancestors)

Phosphorus Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Masking description is for Part B only - Parts A and C are Open Label, so have no masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 10, 2017
• Study Start: August 17, 2017
• Primary Completion: January 3, 2019
• Study Completion: January 3, 2019
• Last Updated: March 25, 2019

Record last verified: 2019-03

Locations

US (4)