Clinical trial NCT04077879: Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP1617 in Healthy Adult Non-Asian and Japanese Subjects Including Assessment of a Food Effect
Official title: A Phase 1 Combined Single and Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP1617 in Healthy Adult Non-Asian and Japanese Subjects Including an Assessment of a Food Effect
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: ASP1617
Food Effect
Pharmacokinetics
Healthy Volunteers
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2019-09-04
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the safety and tolerability of single ascending oral doses of ASP1617 in healthy adult non-Asian and Japanese male and female participants.

This study also evaluate the pharmacokinetics and determine the effect of food on the pharmacokinetics of a single oral dose of ASP1617.

Detailed description: After a screening period of up to 28 days prior to study drug administration, eligible participants will be residential for a single period of 8 days/7 nights in Part 1: single ascending dose, and 21 days/20 nights in Part 2 multiple ascending dose.

Eligibility criteria: Inclusion Criteria:

* For cohorts that enroll non-Asian subjects, subject does not have East Asian (China, Hong Kong, Macau, Japan, Mongolia, North Korea, South Korea and Taiwan) ancestries.
* For cohorts that enroll Japanese subjects, subject is first generation Japanese, born in Japan with 4 grandparents of Japanese descent, and must have resided outside of Japan for ≤ 10 years.
* Subject has a body mass index (BMI) range of 18.5 to 32.0 kg/m2, inclusive and weighs at least 50 kg at screening.
* Female subject is not pregnant and at least 1 of the following conditions apply:

  * Not a woman of childbearing potential (WOCBP)
  * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final investigational product (IP) administration.
* Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
* Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.
* Male subject with female partner(s) of child-bearing potential (including breastfeeding partner\[s\]) must agree to use contraception throughout the treatment period and for 30 days after final IP administration.
* Male subject must not donate sperm during the treatment period and for 30 days after final IP administration.
* Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.
* Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

* Subject has received any investigational therapy 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 ASP1617 or any components of the formulation used.
* Subject has had previous exposure with ASP1617.
* Subject has any of the liver function tests (alkaline phosphatase \[ALP\], ALT, AST, gamma glutamyl transferase and TBL) above the upper linit of normal (ULN) on day -1. In such a case, the assessment may be repeated once.
* Subject has creatinine level outside normal limits on day -1. In such a case, the assessment may be repeated once.
* 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 first IP 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 or fungal infection within 1 week prior to day -1.
* Subject has any clinically significant abnormality following the physical examination, 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) on day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate may be taken.
* Subject has a mean QTcF of \> 430 msec (for male subjects) and \> 450 msec (for female subjects) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG may be taken.
* Subject has used any prescribed or nonprescribed drugs in the 2 weeks prior to first IP administration, except for occasional use of acetaminophen (up to 2 g/day) topical dermatological products, including corticosteroid products, hormonal contraceptives or hormone replacement therapy (HRT).
* Subject has smoked, used tobacco-containing products and nicotine or nicotine-containing products (e.g., electronic vapes) within 6 months prior to screening.
* Subject has a history of consuming \> 14 units for male subjects or \> 7 units for female subjects of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within 2 years prior to screening or the subject tests positive for alcohol at screening or on day -1.
* Subject has used any drugs of abuse within 3 months prior to day -1 or the subject tests positive for drugs of abuse at screening or on day -1.
* Subject has used any inducer of metabolism in the 3 months prior to day -1.
* Subject has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within 7 days prior to day -1 and/or received a transfusion of any blood or blood products within 60 days.
* Subject has a positive serology test for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
* Subject is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
* Subject has received any Coronavirus Disease 2019 (COVID-19) vaccines within 14 days prior to first IP administration.
* Subject has received any Coronavirus Disease 2019 (COVID-19) vaccines within 14 days prior to first IP administration.

Primary outcomes:
measure: Number of participants with adverse events (AEs) in Part 1
timeFrame: Up to Day 16
measure: Number of participants with laboratory value abnormalities and/or AEs in Part 1
timeFrame: Up to Day 16
measure: Number of participants with vital sign abnormalities and/or AEs in Part 1
timeFrame: Up to Day 16
measure: Number of participants with electrocardiogram (ECG) abnormalities and/or AEs in Part 1
timeFrame: Up to Day 16
measure: Number of participants with AEs in Part 2
timeFrame: Up to Day 29
measure: Number of participants with laboratory value abnormalities and/or AEs in Part 2
timeFrame: Up to Day 29
measure: Number of participants with vital sign abnormalities and /or AEs in Part 2
timeFrame: Up to Day 29
measure: Number of participants with 12-ECG abnormalities and/or AEs in Part 2
timeFrame: Up to Day 29
Secondary outcomes:
measure: Part 1: Pharmacokinetics (PK) of ASP1617 in plasma: area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
timeFrame: Up to Day 7
measure: Part 1: PK of ASP1617 in plasma: AUC from the time of dosing to the last measurable concentration (AUClast)
timeFrame: Up to Day 7
measure: Part 1: PK of ASP1617 in plasma: maximum concentration (Cmax)
timeFrame: Up to Day 7
measure: Part 2 (first dose): PK of ASP1617 in plasma: AUC from the time of dosing to 12 hours (AUC12)
timeFrame: Up to 12 hours
measure: Part 2 (first dose and last dose): PK of ASP1617 in plasma: Cmax
timeFrame: Up to Day 17
measure: Part 2 (last dose): PK of ASP1617 in plasma: AUC during a dosing interval, where tau(τ) is the length of the dosing interval (AUCtau)
timeFrame: Up to Day 17
measure: Part 2 (last dose): PK of ASP1617 in plasma: accumulation ratio calculated using AUC (Rac(AUC))
timeFrame: Up to Day 17
measure: PK of ASP1617 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Up to Day 17
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Group / Parexel
state: California
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Senior Director
role: STUDY_DIRECTOR
References: