A Phase I, Single-Centre, Randomized, Double-Blind, Placebo Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ARA 290 Administered Intravenously to Healthy Subjects, and extension in renal patients

1. Subjects must be 18-65 years of age (inclusive);
2. Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive) and body weight between 50 kg and 90 kg (inclusive);
3. History of good physical and mental health;
4. Subject has no clinically significant abnormality on the electrocardiogram performed;
5. Subject is a non-smoker or has not used nicotine/nicotine-containing products for at least 3 months;
6. Subject is able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff;
7. Subject is willing to comply with study restrictions.;Renal patients: creatinin clearance between 30 and 60 mL/min, other criteria comparable to healthy volunteers.

1. Clinically relevant abnormal laboratory results, ECG, vital signs, or physical findings;
2. Subject has a semi recumbent systolic blood pressure of >150 mmHg and or diastolic blood pressure of > 90 mmHg;
3. Subject has an estimated creatinin clearance <80 mL/min based on the Cockcroft-Gault equation.
4. Positive test for hepatitis B, C or HIV;
5. Positive pregnancy test;
6. Male subjects must consent to use a medically acceptable method of contraception throughout the entire study period and for 3 months after the study is completed. Female subjects must be either post-menopausal (last menstrual period > 2 years ago and FSH > 25 IU/L), surgically sterilized (> 6 months ago), or hysterectomized;
7. History of alcoholism or substance abuse within three years prior to screening;
8. Positive drug or alcohol test;
9. Male subjects habitually using more than 21 units of alcohol per week and female subjects using more than 14 units of alcohol per week;
10. Subject is unable to refrain from or anticipates the use of prescription medication in the period beginning one week prior to administration of the initial dose of the study drug until the post study visit;
11. Subject has a history of severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food;
12. Subjects that received a vaccination or immunization within the last month;
13. Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug;
14. Subject who has undergone major surgery within three months prior to screening;
15. Donation or loss of blood (> 500 mL) within 3 months prior to screening;
16. Subjects who have a reaction to the negative control of the histamine test when tested on Day -1;
17. Any abnormalities on the back of the subject which would interfere with the histamine skin prick test as judged by the investigator (e.g. persons with dermatographism, eczema, tattoos or with dark skin-tones which would inhibit clear determination of wheal and flare for histamine assay);
18. Inadequate venous accessibility as judged by clinicians (physician or nurse).
19. Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.;Renal patients: criteria comparable with healthy volunteers, except for conditions related to chronic kidney disease.