A First in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of ONO-2808-01 in Healthy Participants

Inclusion criteria

• Able to provide fully informed written consent.
• 18-55 years (Part A & C) or ≥65 years (Part B).
• Male and female participants (Women of non-child bearing potential (WONCBP)).
• Agree to use an effective method of contraception.
• No clinically significant medical history and no abnormal physical examination, laboratory profiles, vital signs or ECG abnormalities, based on the Screening examination.
• Body mass index (BMI) of ≥18.5 to <30 kg/m2 and a body weight of at least 50 kg for males and 45 kg for females to a maximum of 100 kg, at the time of screening.
• Estimated Creatinine Clearance (CrCL, Cockcroft-Gault equation) ≥90 mL/min at Screening. In Part B only, an estimated CrCL of ≥60mL/min at Screening.

Exclusion criteria

• Mentally or legally incapacitated or with significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical, surgical or psychiatric condition (including history of suicidal behaviour) or objection by General Practitioner (GP) to participant entering trial.
• Liver chemistry values above the upper limit of normal (ULN) at Screening or admission.
• Sensitivity to the study drug.
• Female who is pregnant or lactating or of childbearing potential.
• History or presence of alcoholism or drug/chemical/substance abuse.
• Evidence of poor venous access as assessed by PI.
• Use of any medication which may affect ONO-2808 pharmacokinetics or pharmacodynamics
• Current smoker or has smoked (including use of tobacco and/or nicotine-containing products) in the previous 3 months
• Positive urine drugs of abuse, cotinine or alcohol results at Screening or admission.
• Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Supine resting blood pressure less than 90/40 millimeter of mercury (mmHg) or greater than 140/90 mmHg (Part A& C) and less than 90/40 mmHg or greater than 160/90 mmHg (Part B).
• Supine resting pulse rate lower than 40 beats per minute (bpm) or higher than 100 bpm.
• Clinically significant history or presence of ECG findings at screening.
• Use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days or five half-lives (whichever is longer) of first dosing and throughout the study.
• Consumption or intake of compounds, food or fluids that are known to be a substrate, inducer or inhibitor of CYP450 for 28 days prior to the first dosing and throughout the study.
• Donation of blood or significant blood loss within 56 days prior to the first dosing, or plasma donation within 7 days prior to the first dosing.
• Participation in another clinical study within the last 3 months (or 5 half-lives of the study drug, whichever is longer) prior to the first dosing.
• Objection by PI
• Participants who are not willing to eat a high fat breakfast

Exclusion criteria

, applicable to all participants undergoing lumbar puncture for CSF collection (Part A & C):

• History of significant back pain, significant kyphosis and or scoliosis or other spinal column deformities.
• History or evidence of fundoscopy suggestive of raised intracranial pressure.
• History or presence of any allergy or contraindication to the local anaesthetic required for participants undergoing lumbar puncture.