A Phase 1 Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics and Safety of ASP8232 (Part 1) and a Multiple Dose, Placebo-controlled Exploratory Safety, Pharmacokinetic and Pharmacodynamic Study in Type 2 Diabetes Mellitus Subjects With Chronic Kidney Disease (Part 2)
Overview
- Phase
- Phase 1
- Intervention
- ASP8232
- Conditions
- Healthy Subjects
- Sponsor
- Astellas Pharma Europe B.V.
- Enrollment
- 55
- Locations
- 3
- Primary Endpoint
- Part 1: PK of ASP8232 in plasma measured by Area Under the concentration-time Curve (AUC) from zero to infinity with extrapolation of the terminal phase (AUCinf)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study consists of two parts.
Part 1 evaluates the effect of renal impairment on the PK and PD of a single dose of ASP8232. In addition, the safety and tolerability will be assessed.
Part 2 evaluates the PK, PD, and safety and tolerability of multiple doses of ASP8232 compared with placebo in Type 2 Diabetes Mellitus (T2DM) subjects with Chronic Kidney Disease (CKD).
Detailed Description
This is a two-part study. Part 1 compares the pharmacokinetics (PK), pharmacodynamics (PD) and safety and tolerability of ASP8232 in healthy subjects with subjects with different degrees of renal impairment; Part 2 is a multiple-dose, placebo-controlled study to evaluate the PK, PD and safety and tolerability of multiple doses of ASP8232 in T2DM subjects with CKD. Part 1: Subjects reside in the clinic for 9 days, receiving a single oral dose of ASP8232 on Day 1 under fasted conditions followed by a 168-hours blood and urine PK/PD sampling period. Subjects are discharged on Day 8 and return to the clinic on Days 10, 12, 14, 21, 28, and 42 for the collection of blood PK/PD samples. An End of Study Visit (ESV) takes place after the last PK sample is collected on Day 56. Part 2: Subjects are admitted to the clinic on Day -2 in order to collect PD urine samples before dosing begins on Day 1. Subjects receive multiple oral doses of ASP8232 or placebo for 28 days. They are discharged on Day 8 and return to the clinic on Days 14 and 21, and Days 27 to 29 for blood PK/PD and urine PD samples. An ESV takes place 14 to 28 days after the last PK/PD sample is collected.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
1: Single dose of ASP8232
Subjects receive a single oral dose of ASP8232
Intervention: ASP8232
2: Multiple doses of ASP8232 or placebo
Subjects receive multiple oral doses of ASP8232 or placebo
Intervention: ASP8232
2: Multiple doses of ASP8232 or placebo
Subjects receive multiple oral doses of ASP8232 or placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1: PK of ASP8232 in plasma measured by Area Under the concentration-time Curve (AUC) from zero to infinity with extrapolation of the terminal phase (AUCinf)
Time Frame: Day 1 to Day 56
Part 1: PK of ASP8232 in plasma measured by AUC from zero up to last time point of observation (AUClast)
Time Frame: Day 1 to Day 56
Part 1: PK of ASP8232 in plasma measured by AUC from 0 to infinity with extrapolation of the terminal phase, unbound fraction (AUCinf,u)
Time Frame: Day 1 to Day 56
Part 1: PK of ASP8232 in plasma measured by maximum concentration (Cmax)
Time Frame: Day 1 to Day 56
Part 1: PK of ASP8232 in plasma measured by AUC from zero up to last time point of observation, unbound fraction (AUClast,u)
Time Frame: Day 1 to Day 56
Part 1: PK of ASP8232 in plasma measured by maximum concentration, unbound fraction (Cmax,u)
Time Frame: Day 1 to Day 56
Part 2: Safety and tolerability of ASP8232 measured by nature, frequency and severity of AEs, vital signs, safety laboratory tests, routine ECG
Time Frame: Screening to End of Study Visit (ESV)
Secondary Outcomes
- Part 1: PD of Vascular adhesion protein-1 (VAP-1) activity in plasma(Day -1 to Day 56)
- Part 1: PD of Total antioxidant status (TAS) in serum(Day -1 to Day 56)
- Part 2: PD of VAP-1 activity in plasma(Day -2 to Day 21 and Day 28 to ESV)
- Part 2: PD of TAS in serum(Day -2 to Day 21 and Day 28 to ESV)
- Part 1: PK profile of ASP8232 in plasma(Day 1 to Day 56)
- Part 1: PK profile of ASP8232 in urine(Day -1 to Day 8)
- Part 2: 24-hour urinary albumin excretion rate (UAER)(Day -1, Day 7 and Day 28)
- Part 1: Safety and tolerability of ASP8232(Screening to Day 56)
- Part 2: PK profile of ASP8232 in urine(Day 1 to Day 8 and Day 28 to Day 29)
- Part 2: PK profile of ASP8232 in plasma(Day 1 to Day 29)