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

NCT02218099 | Completed Phase 1

• 2 other identifiers: 8232-CL-00022013-000680-89
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 3

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).

Conditions

Healthy Subjects; Pharmacokinetics of ASP8232; Pharmacodynamics of ASP8232; Chronic Kidney Disease (CKD); Type 2 Diabetes Mellitus (T2DM)

Keywords

ASP8232; Multiple doses; Phase 1; Single dose

Outcome Measures

Primary Outcomes (7)

• 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)

  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)

  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)

  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)

  Day 1 to Day 56

• Part 1: PK of ASP8232 in plasma measured by maximum concentration (Cmax)

  Day 1 to Day 56

• Part 1: PK of ASP8232 in plasma measured by maximum concentration, unbound fraction (Cmax,u)

  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

  Screening to End of Study Visit (ESV)

Secondary Outcomes (10)

• 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 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 1: Safety and tolerability of ASP8232

  Screening to Day 56

Study Arms (2)

1: Single dose of ASP8232

EXPERIMENTAL

Subjects receive a single oral dose of ASP8232

Drug: ASP8232

2: Multiple doses of ASP8232 or placebo

EXPERIMENTAL

Subjects receive multiple oral doses of ASP8232 or placebo

Drug: ASP8232; Drug: Placebo

Interventions

ASP8232 DRUG

Oral

1: Single dose of ASP8232; 2: Multiple doses of ASP8232 or placebo

Placebo DRUG

Oral

2: Multiple doses of ASP8232 or placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) (\> 14 units of alcohol for female subjects) within 3 months prior to admission to the Clinical Unit.
• Subject uses drugs of abuse within 3 months prior to admission to the Clinical Unit.
• Subject regularly uses any inducer of metabolism (e.g. barbiturates, rifampin ) in the 3 months prior to admission to the Clinical Unit.
• Subject had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on day -1.
• Subject has positive serology test for Hepatitis B Surface Antigen (HBsAg), anti-Hepatitis A virus (anti-HAV \[IgM\]), anti-Hepatitis C virus (anti-HCV) or anti- Human immunodeficiency virus 1 + 2 (anti-HIV 1+2).
• Subject participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives whichever is longer, prior to the initiation of screening.
• Subject is an employee of the Astellas Group or Clinical Research Organization (CRO) involved in the study.
• Healthy Subjects:

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (3)

Site: 35901

Sofia, 1612, Bulgaria

Location

Site: 37301

Chisinau, Moldova

Location

Site: 40001

Bucharest, 10731, Romania

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2

Interventions

ASP8232

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Central contact

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 15, 2014
• Study Start: September 16, 2013
• Primary Completion: September 9, 2014
• Study Completion: September 9, 2014
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1); BU (1); MO (1)