A Study of MA-0217 (ASP1128) in Healthy Adult Subjects and Healthy Elderly Subjects

NCT04742517 | Completed Phase 1 FDA Drug

• 1 other identifier: 1128-CL-0101
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of single ascending intravenous doses of ASP1128 in healthy adult male and female subjects and multiple ascending intravenous doses of ASP1128 in healthy adult male and female subjects and healthy elderly male and female subjects. This study will also evaluate the pharmacokinetics and the effect on the QT interval using Fridericia's correction formula (QTcF) in these subjects.

Conditions

Healthy Volunteers

Keywords

MA-0217; Healthy Volunteers; Pharmacokinetics; ASP1128

Outcome Measures

Primary Outcomes (9)

• Number of participants with Adverse Events (AEs) in Part 1

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. In order to identify any events that may be associated with study procedures and could lead to a change in the conduct of the study, AEs will be collected even if the subject has not received study drug treatment.

  Up to Day 16

• Number of participants with laboratory value abnormalities and/or AEs in Part 1

  Number of participants with potentially clinically significant laboratory values.

  Up to Day 16

• Number of participants with vital sign abnormalities and/or AEs in Part 1

  Number of participants with potentially clinically significant vital sign values.

  Up to Day 16

• Number of participants with electrocardiogram (ECG) abnormalities and/or AEs in Part 1

  Number of participants with potentially clinically significant 12-ECG values.

  Up to Day 16

• Number of participants with real-time cardiac monitoring (cardiac telemetry) abnormalities and/or AEs in Part 1

  Number of participants with potentially clinically significant cardiac telemetry values.

  On Day 1

• Number of participants with AEs in Part 2

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. In order to identify any events that may be associated with study procedures and could lead to a change in the conduct of the study, AEs will be collected even if the subject has not received study drug treatment.

  Up to Day 19

• Number of participants with laboratory value abnormalities and/or AEs in Part 2

  Number of participants with potentially clinically significant laboratory values.

  Up to Day 19

• Number of participants with vital sign abnormalities and /or AEs in Part 2

  Number of participants with potentially clinically significant vital sign values.

  Up to Day 19

• Number of participants with ECG abnormalities and/or AEs in Part 2

  Number of participants with potentially clinically significant 12-ECG values.

  Up to Day 19

Secondary Outcomes (29)

• Part 1: Pharmacokinetics (PK) of ASP1128 in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)

  Up to 72 hours post-dose on Day 1

• Part 1: PK of ASP1128 in plasma: AUC from the time of dosing to the last measurable concentration (AUClast)

  Up to 72 hours post-dose on Day 1

• Part 1: PK of ASP1128 in plasma: percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf(%extrap))

  Up to 72 hours post-dose on Day 1

• Part 1: PK of ASP1128 in plasma: maximum concentration (Cmax)

  Up to 72 hours post-dose on Day 1

• Part 1: PK of ASP1128 in plasma: total systemic clearance after intravenous dosing (CL)

  Up to 72 hours post-dose on Day 1

Study Arms (4)

Single ascending dose of ASP1128

EXPERIMENTAL

Participants (6 for each cohort) will receive a single dose of ASP1128.

Drug: ASP1128

Single ascending dose of Placebo

PLACEBO COMPARATOR

Participants (2 for each cohort) will receive a single dose of matching Placebo.

Drug: Placebo

Multiple ascending dose of ASP1128

EXPERIMENTAL

Participants (9 for each cohort) will receive daily doses of ASP1128 for 7 consecutive days.

Drug: ASP1128

Multiple ascending dose of Placebo

PLACEBO COMPARATOR

Participants (3 for each cohort) will receive matching Placebo for 7 consecutive days.

Drug: Placebo

Interventions

ASP1128 DRUG

Intravenous

Also known as: MA-0217

Multiple ascending dose of ASP1128; Single ascending dose of ASP1128

Placebo DRUG

Intravenous

Multiple ascending dose of Placebo; Single ascending dose of Placebo

Eligibility Criteria

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

You may qualify if:

• For adult subjects (cohorts 1.1 to 1.8 and cohorts 2.1 to 2.5):
• Subject is a healthy adult male or female subject 18 to 55 years of age, inclusive at screening.
• Subject has a body mass index (BMI) range of 18.5 to 32.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• For elderly subjects (cohort 2.6):
• Subject is a healthy elderly male or female subject ≥ 65 years of age at screening.
• Subject has a BMI range of 18.5 to 32.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Subject is considered an adult according to local regulation at the time of signing informed consent.
• Female subject must either be of nonchildbearing potential:
• Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or
• Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy or bilateral oophorectomy), OR, if of childbearing potential:
• Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
• Have a negative blood pregnancy test at screening and a negative urine pregnancy test on day -1
• If heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study period and for 28 days after the final study drug administration
• Female subject must agree not to breastfeed starting at screening and throughout the study period and for 28 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.

You may not qualify if:

• Subject has received investigational drug within 28 days or 5 half-lives, whichever is longer, prior to screening.
• Subject has any condition which makes the subject unsuitable for study participation.
• Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP1128 or any components of the formulation used.
• Subject has had previous exposure with ASP1128.
• Subject has unsuitable or difficult venous access to support the intravenous infusion(s) and/or required blood draws.
• Subject has any of the liver function tests (LFTs; aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], gamma-glutamyl transferase and total bilirubin \[TBL\]) above the upper limit of normal (ULN) at screening or on day -1. In such a case, the assessment may be repeated once.
• Subject has total creatine kinase (CK) \> 1.5 × ULN or cardiac troponin I above the ULN at day -1.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to study drug administration.
• Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal and/or other major disease or malignancy.
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to day -1.
• Subject has any clinically significant abnormality following the physical examination, electrocardiogram (ECG) and protocol-defined clinical laboratory tests at screening or on day -1.
• Subject has a mean pulse \< 45 or \> 90 bpm; mean systolic blood pressure (SBP) \> 140 mmHg; mean diastolic blood pressure (DBP) \> 90 mmHg (measurements taken in triplicate after subject has been resting in the supine position for at least 5 minutes; pulse will be measured automatically) at screening or on day -1. For elderly subjects the following criteria apply: SBP \> 160 mmHg, DBP \> 100 mmHg. If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
• Subject has a mean QT interval using Fridericia's correction formula (QTcF) interval of \> 430 msec (for males) and \> 450 msec (for females) at screening or on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
• Subject has used any prescribed or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks prior to study drug administration, except for occasional use of acetaminophen (up to 2 g/day), hormonal contraceptives and hormone replacement therapy.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Parexel Early Phase Clinical Unit - Los Angeles

Glendale, California, 91206, United States

Location

Related Publications (1)

• Taniuchi Y, van Till JWO, Wojtkowski T, Toyoshima J, Koibuchi A, Sargent B, Han D. Single- and Multiple-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP1128, a Novel Peroxisome Proliferator-activated Receptor delta Modulator, in Healthy Participants. Clin Pharmacol Drug Dev. 2023 Aug;12(8):810-818. doi: 10.1002/cpdd.1236. Epub 2023 Mar 21.

  PMID: 36942507 DERIVED

MeSH Terms

Interventions

ASP1128

Study Officials

• Medical Director

  Astellas Pharma Europe BV (APEB)

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 8, 2021
• Study Start: November 20, 2017
• Primary Completion: September 7, 2018
• Study Completion: September 7, 2018
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)