A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of ASP8232 in Subjects With Renal Impairment and in Type 2 Diabetes Mellitus Subjects With Chronic Kidney Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02218099
• Date of registration: 14/08/2014
• Prospective Registration: No
• Primary sponsor: Astellas Pharma Europe B.V.
• Public title: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of ASP8232 in Subjects With Renal Impairment and in Type 2 Diabetes Mellitus Subjects With Chronic Kidney Disease
• Scientific title: 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)
• Date of first enrolment: September 16, 2013
• Target sample size: 55
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02218099
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

Bulgaria, Moldova, Republic of, Romania

Contacts

• Name: Central contact
• Affiliation: Astellas Pharma Europe B.V.

Key inclusion & exclusion criteria

Main Inclusion: Part 1

- Independent Ethics Committee (IEC)-approved written Informed Consent and privacy
language as per national regulations must be obtained from the subject or legally
authorized representative prior to any study-related procedures (including withdrawal
of prohibited medication, if applicable).

- Male subject and his female spouse/partner who is of childbearing potential must be
using highly effective contraception consisting of 2 forms of birth control (1 of
which must be a barrier method) starting at screening and continue throughout the
study period and for 28 days (or 5 half-lives of the study drug whichever is longer)
after final study drug administration.

- Male subject must not donate sperm starting at screening and throughout the study
period and for at least 90 days after final study drug administration.

- Female subject must be either:

- post-menopausal (defined as at least one year without any menses) prior to
screening, or

- premenarchal prior to screening, or

- documented surgically sterile or status post hysterectomy (at least 1 month
before screening), or

- if of childbearing potential, must have a negative urine pregnancy test at
screening and must be using highly effective contraception. All females of
childbearing potential will be required to use highly effective contraception
consisting of 2 forms of birth control (1 of which must be a barrier method)
starting at screening and throughout the study period and for 28 days (or 5
half-lives of the study drug whichever is longer) after final study drug
administration.

- Female subject must not be lactating, and must not be breast feeding at screening or
during the study period and for 28 days [or 5 half-lives of the study drug whichever
is longer] after final study drug administration.

- Female subject must not donate ova starting at screening and throughout the study
period and for 28 days [or 5 half-lives of the study drug whichever is longer] after
final study drug administration.

- Subject agrees not to participate in another interventional study while on treatment.

Healthy Subjects:

- Subject must have pre dose eGFR values (based on the MDRD method) at screening and day
-1 higher or equal to 80 mL/min/1.73 m2.

Renal Impaired Subjects:

- Subject must have pre dose eGFR values (based on the MDRD method) at screening and day
-1 of 15 to < 30 mL/min/1.73 m2, 30 to

< 60 mL/min/1.73 m2 or 60 to < 80 mL/min/1.73 m2 for severe, moderate or mild renal
impaired subjects, respectively.

Part 2 Inclusion:

- Independent Ethics Committee (IEC)-approved written Informed Consent and privacy
language as per national regulations must be obtained from the subject or legally
authorized representative prior to any study-related procedures (including withdrawal
of prohibited medication, if applicable).

- Subject has either known or confirmed T2DM with CKD for at least 1 year [screening].

- Subject is = 35 and = 80 years of age.

- Male subject and his female spouse/partner who is of childbearing potential must be
using highly effective contraception consisting of 2 forms of birth control (1 of
which must be a barrier method) starting at screening and continue throughout the
study period and for 28 days (or 5 half-lives of the study drug whichever is longer)
after final study drug administration.

- Male subject must not donate sperm starting at screening and throughout the study
period and for at least 90 days after final study drug administration.

- Female subject must be either

- post-menopausal (defined as at least one year without any menses) prior to
Screening, or

- premenarchal prior to screening, or

- documented surgically sterile or status post hysterectomy (at least 1 month
before screening), or

- if of childbearing potential, must have a negative urine pregnancy test at
screening and must be using highly effective contraception1. All females of
childbearing potential will be required to use highly effective contraception
consisting of 2 forms of birth control (1 of which must be a barrier method)
starting at screening and throughout the study period and for 28 days (or 5
half-lives of the study drug whichever is longer) after final study drug
administration.

- Female subject must not be lactating, and must not be breast feeding at screening or
during the study period and for 28 days (or 5 half-lives of the study drug whichever
is longer) after final study drug administration.

- Female subject must not donate ova starting at screening and throughout the study
period and for 28 days (or 5 half-lives of the study drug whichever is longer] after
final study drug administration.

- Subject is on a stable therapy with ACE inhibitors or ARB for at least 3 months
[screening].

- Subject is on a stable anti-hyperglycaemia therapy, e.g. with Metformin, SUD, TZD or
DPP-4 inhibitor.

- Subject's eGFR is between 15-60 mL/min/1.73 m2 (based on the MDRD method).

- Subject's HbA1c level is lower than 7.5% at clinic admission on day -2.

- Subject has a stable blood pressure for at least 3 to 6 months prior to enrolment.

- Subject's UACR is higher than 30 mg/g at clinic admission on day -2.

Part 1 Exclusion:

All Subjects:

- Female subject who has been pregnant within 6 months before screening or breast
feeding within 3 months before screening.

- Subject has a known or suspected hypersensitivity to ASP8232, or any components of the
formulation used.

- Subject has any clinically significant history of allergic conditions (including drug
allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated,
asymptomatic, seasonal allergies at time of dosing).

- Subject has Gilbert's syndrome.

- Subject has/had febrile illness or symptomatic, viral, bacterial (including upper
respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to
clinic check in.

- Subject has a history of smoking more than 10 cigarettes (or equivalent amount of
tobacco) per day within 3 months prior to admission to the Clinical Unit.

- Subject has a history of drinking more than 21 units of alcohol per week (1 unit = 10
g pure alcohol = 250


Age minimum: 35 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pharmacokinetics of ASP8232

Type 2 Diabetes Mellitus (T2DM)

Chronic Kidney Disease (CKD)

Healthy Subjects

Pharmacodynamics of ASP8232

Intervention(s)

Drug: ASP8232

Drug: Placebo

Primary Outcome(s)

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 maximum concentration, unbound fraction (Cmax,u) [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 AUC from zero up to last time point of observation, unbound fraction (AUClast,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)]

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 maximum concentration (Cmax) [Time Frame: Day 1 to Day 56]

Secondary Outcome(s)

Part 2: PK profile of ASP8232 in plasma [Time Frame: Day 1 to Day 29]

Part 1: PK profile of ASP8232 in plasma [Time Frame: Day 1 to Day 56]

Part 2: PD of TAS in serum [Time Frame: Day -2 to Day 21 and Day 28 to ESV]

Part 1: Safety and tolerability of ASP8232 [Time Frame: Screening to Day 56]

Part 2: PK profile of ASP8232 in urine [Time Frame: Day 1 to Day 8 and Day 28 to Day 29]

Part 1: PD of Vascular adhesion protein-1 (VAP-1) activity in plasma [Time Frame: Day -1 to Day 56]

Part 1: PK profile of ASP8232 in urine [Time Frame: Day -1 to Day 8]

Part 1: PD of Total antioxidant status (TAS) in serum [Time Frame: Day -1 to Day 56]

Part 2: 24-hour urinary albumin excretion rate (UAER) [Time Frame: Day -1, Day 7 and Day 28]

Part 2: PD of VAP-1 activity in plasma [Time Frame: Day -2 to Day 21 and Day 28 to ESV]

Secondary ID(s)

8232-CL-0002

2013-000680-89

Source(s) of Monetary Support

Please refer to primary and secondary sponsors