DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis

Daiichi Sankyo

Status and phase: Completed; Phase 1

Conditions: Hyperphosphatemia

Treatments: Drug: DS-2330b Tablet; Drug: DS-2330b PIB; Drug: Placebo; Drug: Sevelamer

Study type: Interventional

Funder types: Industry

Identifiers

NCT03305471

DS2330-A-U103

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

40 participants in 7 patient groups, including a placebo group

Part A: DS-2330b PIB, then Tablet

Experimental group

Description:

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.

Treatment:

Drug: DS-2330b PIB

Drug: DS-2330b Tablet

Part A: DS-2330b Tablet, then PIB

Experimental group

Description:

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.

Treatment:

Drug: DS-2330b PIB

Drug: DS-2330b Tablet

Part B: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Part B: DS-2330b PIB

Experimental group

Description:

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

Treatment:

Drug: DS-2330b PIB

Part B: DS-2330b PIB + Sevelamer

Experimental group

Description:

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

Treatment:

Drug: DS-2330b PIB

Drug: Sevelamer

Part B: Placebo + Sevelamer

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Sevelamer

Part C: DS-2330b Tablet + Sevelamer

Experimental group

Description:

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

Treatment:

Drug: DS-2330b Tablet

Drug: Sevelamer