DS2330b Alone and With Sevelamer in Patients on Chronic Hemodialysis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hyperphosphatemia

Intervention / Treatment
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* Drug: DS-2330b PIB
* Drug: Placebo
* Drug: Sevelamer
* Drug: DS-2330b Tablet


Participation Criteria
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Eligibility Criteria
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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: 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 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: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hemodialysis, Investigational drug