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

NCT03108755 | Completed Phase 1

• 2 other identifiers: 7713-CL-00012016-004845-10
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Volunteers

Keywords

ASP7713

Outcome Measures

Primary Outcomes (9)

• Safety as assessed by nature, frequency and severity of Adverse Events (Part 1 and Part 2)

  Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). Treatment Emergent Adverse Event (TEAE) is defined as any AE starting or worsening at any time from first dosing until last scheduled procedure.

  Part 1: Up to Day 16 / Part 2: Up to Day 29

• Number of Participants with Vital Sign Abnormalities and/or Adverse Events (Part 1 and Part 2)

  Number of participants with potentially clinically significant vital sign values.

  Part 1: Up to Day 16 / Part 2: Up to Day 29

• Number of Participants with Laboratory Value Abnormalities and/or Adverse Events (Part 1 and Part 2)

  Number of participants with potentially clinically significant laboratory values.

  Part 1: Up to Day 16 / Part 2: Up to Day 29

• Safety assessed by routine 12-Lead Electrocardiogram (ECG) (Part 1 and Part 2)

  Any clinically significant adverse changes on the ECG will be reported as an AE.

  Part 1: Up to Day 16 / Part 2: Up to Day 29

• Safety assessed by continuous 12-Lead Electrocardiogram (ECG) (Part 1 and Part 2)

  Any clinically significant adverse changes on the ECG will be reported as an AE.

  Part 1: Up to Day 2 / Part 2: Up to Day 17

• Safety assessed by Real-time cardiac monitoring (telemetry) (Part 1)

  Number of participants with potentially clinically significant telemetry abnormalities.

  Part 1: Up to Day 1

• Safety assessed by Cardiac troponin T (cTnT) (Part 1 and Part 2)

  Number of participants with potentially clinically significant cTnT abnormalities. Cardiac troponin T is a component of the contractile apparatus of myocardial cells and is expressed almost exclusively in the heart.

  Part 1: Up to Day 16 / Part 2: Up to Day 29

• Safety assessed by Cardiac troponin I (cTnI) (Part 1 and Part 2)

  Number of participants with potentially clinically significant cTnI abnormalities. Cardiac troponin I is a component of the contractile apparatus of myocardial cells and is expressed almost exclusively in the heart.

  Part 1: Up to Day 16 / Part 2: Up to Day 29

• Safety assessed by Orthostatic challenge test (OCT) (Part 1 and Part 2)

  Number of participants with potentially clinically significant OCT changes will be reported as an AE.

  Part 1: Up to Day 1 / Part 2: Up to Day 14

Secondary Outcomes (31)

• Part 1: Pharmacokinetics (PK) of ASP7713 in plasma: area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf)

  Up to Day 7

• Part 1: PK of ASP7713 in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

  Up to Day 7

• Part 1: PK of ASP7713 in plasma: percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf(%extrap))

  Up to Day 7

• Part 1: PK of ASP7713 in plasma: maximum concentration (Cmax)

  Up to Day 7

• Part 1: PK of ASP7713 in plasma: apparent total systemic clearance after extravascular dosing (CL/F)

  Up to Day 7

Study Arms (6)

ASP7713 Single Ascending Dose

EXPERIMENTAL

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.

Drug: ASP7713

Placebo Single Ascending Dose

PLACEBO COMPARATOR

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.

Drug: Placebo

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

EXPERIMENTAL

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.

Drug: ASP7713

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

PLACEBO COMPARATOR

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.

Drug: Placebo

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

EXPERIMENTAL

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.

Drug: ASP7713

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

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

ASP7713 DRUG

oral

ASP7713 Multiple Ascending Dose (Adults: 18-55 years); ASP7713 Multiple Ascending Dose (Elderly: 65 years or older); ASP7713 Single Ascending Dose

Placebo DRUG

oral

Placebo Multiple Ascending Dose (Adults: 18-55 years); Placebo Multiple Ascending Dose (Elderly: 65 years or older); Placebo Single Ascending Dose

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (1)

Site GB44001

Harrow, Middlesex, HA 1 3UJ, United Kingdom

Location

Study Officials

• Medical Monitor

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 11, 2017
• Study Start: May 23, 2017
• Primary Completion: August 25, 2017
• Study Completion: August 25, 2017
• Last Updated: March 7, 2018

Record last verified: 2018-03

Locations

GB (1)