A Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP7713 in Healthy Non-Japanese Adult and Elderly Subjects and Healthy Japanese Adult Subjects

NCT ID: NCT03108755

Last Updated: 2018-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-23
• Study Completion Date: 2017-08-25

Brief Summary

This is a combined Single and Multiple Ascending Oral Dose Study. Part 1 is a Single Ascending Dose (SAD) and Part 2 is Multiple Ascending Dose (MAD).

The purpose of the study is to evaluate the safety and tolerability of single and multiple ascending oral doses of ASP7713 in healthy non-Japanese (Part 1) and Japanese (Part 2) adult participants and non-Japanese elderly participants (Part 2).

This study will also evaluate the pharmacokinetics of single and multiple ascending oral doses of ASP7713 in non-Japanese (Part1) and Japanese (Part 2) adult participants and non-Japanese elderly participants (Part 2) as well as the effect of a single and multiple oral dose of ASP7713 on the QT interval using Fridericia's Correction (QTcF).

In addition, this study will evaluate a potential racial difference in safety, tolerability and pharmacokinetics of multiple oral doses of ASP7713 in healthy non-Japanese and Japanese adult participants (Part 2).

Detailed Description

There will be a residential period for Parts 1 and 2. Part 1: Eligible participants will be residential for a single period of 5 days and 4 nights. Participants will be discharged on day 4 on the condition that all required assessments have been performed and that there are no medical reason for a longer stay in the clinical unit.

Part 2: Eligible participants will be residential for a single period of 18 days and 17 nights. Participants will be discharged on day 17 on the condition that there are no medical reason for a longer stay in the clinical unit.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

ASP7713 Single Ascending Dose

Successive cohorts of 8 non-Japanese participants (6 ASP7713/ 2 Placebo / 1-7 cohorts) will be started on a fixed single dose of ASP7713 or matching Placebo. The first two participants will receive either ASP7713 or matching placebo. If no safety issues are observed in the first 24 hours in the first two participants, then the remaining six participants will be dosed. Safety, tolerability and available Pharmacokinetic data from proceeding cohorts will be assessed for dose escalation.

Group Type: EXPERIMENTAL

ASP7713

Intervention Type: DRUG

oral

Placebo Single Ascending Dose

Successive cohorts of 8 non-Japanese participants (6 ASP7713/ 2 Placebo / 1-7 cohorts) will each be started on a single fixed dose of ASP7713 or matching Placebo. The first two participants will receive either ASP7713 or matching placebo. If no safety issues are observed in the first 24 hours in the first two participants, then the remaining six participants will be dosed. Safety, tolerability and available Pharmacokinetic data from proceeding cohorts will be assessed for dose escalation.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral

ASP7713 Multiple Ascending Dose (Adults: 18-55 years)

Successive cohorts of 16 participants consisting of 8 non-Japanese and 8 Japanese (12 ASP7713/ 4 Placebo /1-3 cohorts) will each be started on a fixed multiple dose of ASP7713 or matching Placebo twice or three times daily for 14 days. Safety, tolerability and available Pharmacokinetic data from proceeding cohorts will be assessed for dose escalation.

Group Type: EXPERIMENTAL

ASP7713

Intervention Type: DRUG

oral

Placebo Multiple Ascending Dose (Adults: 18-55 years)

Successive cohorts of 16 participants consisting of 8 non-Japanese and 8 Japanese (12 ASP7713/ 4 Placebo /1-3 cohorts) will each be started on a fixed multiple dose of ASP7713 or matching Placebo twice or three times daily for 14 days. Safety, tolerability and available Pharmacokinetic data from proceeding cohorts will be assessed for dose escalation.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral

ASP7713 Multiple Ascending Dose (Elderly: 65 years or older)

Dosing of the non-Japanese elderly cohort will commence after having established the safety and tolerability of corresponding dose in adults male and female participants.

Group Type: EXPERIMENTAL

ASP7713

Intervention Type: DRUG

oral

Placebo Multiple Ascending Dose (Elderly: 65 years or older)

Dosing of the non-Japanese elderly cohort will commence after having established the safety and tolerability of corresponding dose in adults male and female participants.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral

Interventions

ASP7713

oral

Intervention Type: DRUG

Placebo

oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject is a healthy non-Japanese adult male or female subject between 18 to 55 years of age, inclusive, at screening or subject is a healthy non-Japanese elderly male or female subject, ≥ 65 years of age and has a body mass index (BMI) range of 18.5 to 30.0 kg/m2, inclusive and weighs at least 50 kg at screening and day -1 OR Subject is a healthy Japanese adult male or female subject between 20 to 55 years of age, inclusive, at screening and has a BMI range of 18.0 to 28.0 kg/m2, inclusive and weighs at least 45 kg at screening and day -1.
• In case of Japanese subject: subject is from Japanese origin. Both parents and all 4 grandparents should be Japanese. The subject should have been born in Japan and should not have lived outside of Japan for more than 10 years.
• Female subject must either:

• Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year without any menses) prior to screening, or Documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, 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, And have a negative pregnancy test at day -1, And if heterosexually active, agree to consistently use 2 forms of birth control (1 of which is a highly effective method and 1 must be a barrier method) 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.
• A sexually active male subject with female partner(s) who are of childbearing potential is eligible if:

• Male subject agrees to use a male condom starting at screening and continue throughout study treatment and for 28 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period and for 28 days after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a male condom for the duration of the pregnancy or for the time the partner is breastfeeding throughout the study period and for 28 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria

• Subject has received 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 assessment or breast feeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP7713, or any components of the formulation used.
• Subject has had previous exposure with ASP7713.
• Subject has any of the liver function tests (LFTs) (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, gamma-glutamyl transferase and total bilirubin [TBL]) above the upper limit of normal (ULN) at day -1. In such a case, the assessment may be repeated once.
• Subject has any of the cardiac troponins (cardiac troponin T [cTnT] and cardiac troponin I [cTnI]) above the ULN at 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 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 investigator's review of the physical examination, electrocardiogram (ECG) and protocol-defined safety laboratory tests at screening or day -1.
• Subject has a mean pulse < 45 or > 90 bpm; mean systolic blood pressure < 90 or > 140 mmHg; mean diastolic blood pressure < 50 or > 90 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) at screening or day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
• Subject has a mean QTcF interval of > 430 msec (for males) and > 450 msec (for females) at screening or day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
• Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of long QT syndrome.
• 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 paracetamol (up to 2 g/day) and except for use of hormonal contraceptives and hormone replacement therapy.
• Subject has smoked or has used tobacco-containing products and nicotine or nicotine-containing products in the past 6 months prior to screening.
• 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 day -1 or the subject tests positive for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or day -1.
• Subject has used any drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) within 3 months prior to day -1.
• Subject has consumed grapefruit/Seville oranges, grapefruit-containing products or Seville orange-containing products within 72 hours prior to admission to the clinical unit.
• Subject has used any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to day -1.
• Subject has had significant blood loss, donated 1 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 day -1.
• Subject has a positive serology test for hepatitis B surface antigen, hepatitis B core antibody, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies, or antibodies to human immunodeficiency virus type 1 and/or type 2 at screening.
• Subject is an employee of the Astellas Group or contract research organization.
• Subject has a history of orthostatic hypotension or a positive orthostatic challenge test which is based on the measurements 3 minutes after standing:

• Systolic blood pressure (SBP) ≥ 20 mmHg decrease from supine and/or
• Diastolic blood pressure (DBP) ≥ 10 mmHg decrease from supine at screening or day -1.
• Subject has any clinically significant abnormalities on cardiac imaging at screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Locations

Site GB44001

Harrow, Middlesex, United Kingdom

Countries

United Kingdom

Other Identifiers

2016-004845-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7713-CL-0001

Identifier Type: -

Identifier Source: org_study_id