A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MA-0211 in Healthy Adult Subjects Including a Food Effect Cohort

Exclusion Criteria

• •Subject participated in any clinical study or has been treated with any investigational drugs within 28 days prior to screening.
• •Subject has any condition which makes the subject unsuitable for clinical 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 MA-0211, or any components of the formulation used.
• •Subject has had previous exposure with MA-0211.
• •Subject has any of the liver function tests (aspartate aminotransferase \[AST\], alanine amino-transferase \[ALT\], alkaline phosphatase \[ALP\], gamma-glutamyl transferase \[GGT\] and total bilirubin \[TBL\]) above the upper limit of normal at day -2. In such a case, the assessment may be repeated once.
• •Subject has total creatine kinase greater than 1.5 times the upper limit of normal or troponin I above the upper limit of normal at day -2.
• •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, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, psychiatric, dermatologic, 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 -2).
• •Subject has any clinically significant abnormality following the investigator's review of the physical examination, ECG and protocol-defined clinical safety laboratory tests at screening or day 2.
• •Subject has a mean heart rate \< 45 or \> 90 beats per minute; mean Systolic blood pressure (SBP) \> 140 mmHg; mean diastolic blood pressure (DBP) \> 90 mmHg at day -2 (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; heart rate will be measured automatically). If the mean heart rate, SBP or DBP exceeds the limits above, 1 additional triplicate can be taken (day -2).
• •Subject has a mean QT interval using Fridericia's correction (QTcF) \> 430ms (for males) and \>450ms (for females) at day 2 or if the subject has any family history of long QT syndrome (LQTS). If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken (day -2).
• •Subject has used any prescribed or nonprescribed drugs (including vitamins, calcium and iron supplements, natural and herbal remedies \[e.g., St. John's Wort\]) in the 2 weeks (or 5 elimination half-lives, whichever is longer) prior to study drug administration, except for occasional use of acetaminophen (up to 2 g/day \[prn\]). In addition, subject has used any peroxisome proliferator-activated receptor (PPAR) ligands such as fibrates and thiazolidinediones in the 4 weeks prior to day -2.
• •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 more than 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 the 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 at screening or day -2 (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates).
• •Subject has used any drugs of abuse within 3 months prior to day -2.
• •Subject has used any inducer of metabolism (e.g., barbiturates, rifampin) in the 3 month prior to day -2.
• •Subject has had significant blood loss, donated 1 unit (500 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 -2.
• •Subject has a positive serology test for hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc), hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies (anti-HCV) or antibodies to human immunodeficiency virus (HIV) type 1 and/or type 2 at screening.
• •Subject anticipates an inability to abstain from caffeine-, xanthine- or grapefruit/Seville orange containing products from at least 24 hours (longer for grapefruit/Seville orange containing products: 72 hours) before screening, and from at least 24 hours (longer for grapefruit/Seville orange containing products: 72 hours) before admission to the clinical unit on day -2 up to and including the End of Study Visit (ESV).
• •Subject is an employee of the Astellas Group or Clinical Research Organization (CRO).