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

Inclusion Criteria:

• 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.

• A sexually active male subject with female partner(s) who is(are) of childbearing potential is eligible for the study if:

  • Agree to use a male condom starting at screening and continue throughout study treatment and for 28 days after the final study drug administration.
  • If the male subject has not had a vasectomy or is not sterile, their female partner(s) is(are) utilizing 1 form of highly effective birth control starting at screening and continue throughout study treatment and for 28 days after the male subject receives their 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 condom for the duration of the pregnancy or time partner(s) is(are) 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 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.
• Subject has used any peroxisome proliferator-activated receptor (PPAR) ligands such as fibrates and thiazolidinediones, including self-medication obtained via the internet, in the 4 weeks prior to study drug administration.
• 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 consuming > 14 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) at screening or on 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 used any inducer of metabolism (e.g., barbiturates and rifampin) in the 3 months prior to day -1.
• Subject has had significant blood loss, donated ≥ 1 unit (450 mL) of blood 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 (HBsAg), hepatitis B core (HBc) antibodies, hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM]), 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, Mitobridge or designated contract research organization (CRO).