Single and Multiple Dosing Study in Hemodialysis Patients With Hyperphosphatemia in Japan

A Phase 1, Single and Multiple Dosing Study to Evaluate Pharmacokinetics and Pharmacodynamics of ASP3325 in Patients With Chronic Kidney Disease and Hyperphosphatemia Undergoing Hemodialysis

The objective of this study is to assess PK, safety and tolerability of a single oral dose of ASP3325 and to assess PD, PK and safety of repeated oral doses of ASP3325 administered t.i.d. before or just after each meal

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Hyperphosphatemia Undergoing Hemodialysis
• Intervention / Treatment: Drug: ASP3325

Detailed Description

[Part 1] This part is an open-label, uncontrolled study to evaluate PK and safety with single dosing of ASP3325 in hemodialysis patients. After washout period of therapeutic medication for hyperphosphatemia, six subjects will receive single oral administration of ASP3325 (Tablet A) on a non-dialysis day (Day 1).

[Part 2] This part is a 2-arm, open-label, uncontrolled study to evaluate PD, PK and safety with dosing ASP3325 Tablet B t.i.d. before or just after each meal.

Eligible subjects at screening will be entered into the washout period for stopping their phosphate-binding treatment. 20 subjects with serum inorganic phosphorus (Pi) level between ≥6.0 and <10.0 mg/dL during the washout period (washout period week 1 or washout period week 2) will be randomized to each treatment group and ASP3325 will be administered for 2 weeks until Day 14.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Site: 4
  • Aichi, Japan
    • Site: 5
  • Ibaraki, Japan
    • Site: 1
  • Ibaraki, Japan
    • Site: 2
  • Shizuoka, Japan
    • Site: 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject who has received maintenance hemodialysis 3 times a week for at least 12 weeks (84 days) prior to the scheduled first day of the washout period.
• Subject who can receive morning dialysis from the start of the washout period to the end of follow-up period. (Part 2)
• Subject with pre-dialysis serum Pi level between ≥6.0 and <10.0 mg/dL and be confirmed increase in serum Pi of ≥1.5 mg/dL after the maximum dialysis interval at the washout period week 1 or 2. (Part 2)
• Subject who did not change the type or dose of any phosphate binder(s), any nutritional supplements or any other drugs with phosphorus reducing action for at least 4 weeks (28 days) prior to the scheduled first day of the washout period.
• Subject who did not receive calcimimetics (e.g., cinacalcet HCl) for at least 12 weeks (84 days) prior to the scheduled first day of the washout period.
• Subject taking native or active vitamin D (including vitamin D analogues), calcitonin agents or PTH agents must be on stable dose for at least 4 weeks (28 days) prior to the scheduled first day of the washout period.

Exclusion Criteria:

• Subject who has a history of severe gastrointestinal disorder, major gastrointestinal surgery, malabsorption considered influential on the absorption of the drug and nutrition in the gastrointestinal tract.
• Subject who has a history of parathyroid intervention (e.g., parathyroidectomy [PTx], percutaneous ethanol injection therapy [PEIT]).
• Subject whose dry weight loss >5% within 12 weeks (84 days) prior to the scheduled start day of the washout period.
• Confirmed serum intact PTH >1000 pg/mL at the start of the washout period (only applicable for Part 2).
• Subject whose last 3 measurement values at the separate day of pre-dialysis systolic/diastolic blood pressure before the scheduled start day of the washout period or during the washout period are all 180 mmHg or higher and 120 mmHg or higher.
• Subject who has severe congestive heart failure (i.e., NYHA cardiac function classification Class III or severer).
• Subject who experienced a myocardial infarction or major surgery excluding vascular access surgery within 12 weeks (84 days) prior to the informed consent signing.
• Subject who has any of liver function tests (ALT, AST, T-Bil) out of range as indicated below at the screening (Part 1) or during the washout period, or patients with a complication of serious hepatic disease (e.g., acute and active chronic hepatitis, liver cirrhosis). AST: >2×ULN, ALT: >2×ULN, T-Bil: >1.25×ULN
• Subject with history or complication of malignant tumor (considered eligible if recurrence has not been observed for at least 5 years).
• Subject with history of serious drug hypersensitivity, such as anaphylactic shock.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part1, ASP3325 Tablet A; ASP3325 tablets A will be orally administered with 150 mL of water in fasting condition on non-dialysis day in Day 1	Drug: ASP3325; oral
Experimental: Part2, ASP3325 Tablet B group 1; ASP3325 tablets B will be orally administered t.i.d. 30 minutes before each meal for 2 weeks	Drug: ASP3325; oral
Experimental: Part2, ASP3325 Tablet B group 2; ASP3325 tablets B will be orally administered t.i.d. 30 minutes just after each meal for 2 weeks	Drug: ASP3325; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessed by adverse events: Part 1		Up to Day 7
Safety assessed by adverse events: Part 2		Up to Day 22
Safety assessed by vital signs: Part 1	Vital signs include body temperature, blood pressure and pulse rate)	Up to Day 7
Safety assessed by vital signs: Part 2	Vital signs include body temperature, blood pressure and pulse rate)	Up to Day 22
Safety assessed by clinical laboratory test: Part 1	Clinical laboratory tests include hematology and biochemistry	Up to Day 7
Safety assessed by clinical laboratory test: Part 2	Clinical laboratory tests include hematology and biochemistry	Up to Day 22
Safety assessed by 12-Lead ECG: Part 1	ECG: electrocardiogram	Up to Day 7
Safety assessed by 12-Lead ECG: Part 2	ECG: electrocardiogram	Up to Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of unchanged ASP3325	Cmax:maximum plasma concentration	Part 1 Before administration, Day 1, 2, 4, 5 and 7
tmax of unchanged ASP3325	tmax = time to reach maximum plasma concentration	Part 1 Before administration, Day 1, 2, 4, 5 and 7
AUClast of ASP3325	AUClast: Area under the Curve of plasma concentration during observation period in each observational day	Part 1 Before administration, Day 1, 2, 4, 5 and 7
AUCinf of ASP3325	AUCinf: Area under the Curve of plasma concentration	Part 1 Before administration, Day 1, 2, 4, 5 and 7
t1/2 of ASP3325	t1/2 = apparent terminal elimination half-life	Part 1 Before administration, Day 1, 2, 4, 5 and 7
Vz/F of ASP3325	Vz/F = apparent volume of distribution	Part 1 Before administration, Day 1, 2, 4, 5 and 7
CL/F of ASP3325	CL/F = oral clearance	Part 1 Before administration, Day 1, 2, 4, 5 and 7
Ctrough of ASP3325	Ctrough = observed trough concentration	Part 2 Before administration, Day 3, 5, 8, 10, 12, 15 and 22
Serum Pi of ASP3325	Serum Pi: serum phosphate concentration before dialysis	Part 2 Day -21, -14, and -7 in washout period, Day 1, 8, 15 and 22
Serum Calcium (adjusted for albumin)	Corrected value of Calcium (Ca) (mg/dL) = Observed value of Ca (mg/dL) + [4-albumin (g/dL)	Part 2 Day -21, -14, and -7 in washout period, Day 1, 8, 15 and 22
Serum concentration of intact PTH before dialysis	PTH = parathyroid hormone	Part 2 Day -21 in washout period, Day 1, 8, 15 and 22
Serum concentration of FGF23	FGF23 = fibroblast growth factor 23	Part 2 Day -21 in washout period, Day 1, 8, 15 and 22

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Medical Director, Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2014
• Primary Completion (Actual): November 4, 2014
• Study Completion (Actual): November 4, 2014

Study Registration Dates

• First Submitted: July 8, 2015
• First Submitted That Met QC Criteria: July 27, 2015
• First Posted (Estimated): July 29, 2015

Study Record Updates

• Last Update Posted (Actual): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: pharmacokinetics; Chronic Kidney Disease; pharmacodynamics; Hyperphosphatemia; ASP3325
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Phosphorus Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia
• Other Study ID Numbers: 3325-CL-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.