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

Ono Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Neurodegenerative Diseases

Treatments: Drug: ONO-2808; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04578028

ONO-2808-01

2019-004693-26 (EudraCT Number)

Details and patient eligibility

About

This is a first in human study to determine the safety, tolerability and pharmacokinetics of ONO-2808 in healthy adult participants. The study will be conducted in 3 parts: Part A, a single-ascending dose part with an assessment of the potential food effects in non-Japanese adult participants; Part B, a single dose part to assess the effect of age in non-Japanese elderly participants; and Part C, a multiple-ascending dose part with ONO-2808 administered to healthy subjects.

Enrollment: 94 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Able to provide fully informed written consent.
2. 18-55 years (Part A & C) or ≥65 years (Part B).
3. Male and female participants (Women of non-child bearing potential (WONCBP)).
4. Agree to use an effective method of contraception.
5. No clinically significant medical history and no abnormal physical examination, laboratory profiles, vital signs or ECG abnormalities, based on the Screening examination.
6. 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.
7. 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

1. Mentally or legally incapacitated or with significant emotional problems at the time of the Screening visit or expected during the conduct of the study.

2. 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.

3. Liver chemistry values above the upper limit of normal (ULN) at Screening or admission.

4. Sensitivity to the study drug.

5. Female who is pregnant or lactating or of childbearing potential.

6. History or presence of alcoholism or drug/chemical/substance abuse.

7. Evidence of poor venous access as assessed by PI.

8. Use of any medication which may affect ONO-2808 pharmacokinetics or pharmacodynamics

9. Current smoker or has smoked (including use of tobacco and/or nicotine-containing products) in the previous 3 months

10. Positive urine drugs of abuse, cotinine or alcohol results at Screening or admission.

11. Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).

12. 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).

13. Supine resting pulse rate lower than 40 beats per minute (bpm) or higher than 100 bpm.

14. Clinically significant history or presence of ECG findings at screening.

15. 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.

16. 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.

17. 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.

18. 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.

19. Objection by PI

20. 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):

21. History of significant back pain, significant kyphosis and or scoliosis or other spinal column deformities.

22. History or evidence of fundoscopy suggestive of raised intracranial pressure.

23. History or presence of any allergy or contraindication to the local anaesthetic required for participants undergoing lumbar puncture.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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94 participants in 8 patient groups, including a placebo group

ONO-2808 Part A - Fasted

Experimental group

Description:

Single ascending doses of ONO-2808 or placebo orally under fasted conditions. Additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial.

Treatment:

Drug: ONO-2808

ONO-2808 Placebo Part A- Fasted

Placebo Comparator group

Description:

Single ascending doses of ONO-2808 or placebo orally under fasted conditions

Treatment:

Drug: Placebo

ONO-2808 Part A - Fed

Experimental group

Description:

Single ascending doses of ONO-2808 or placebo orally under fed conditions

Treatment:

Drug: ONO-2808

ONO-2808 Placebo Part A - Fed

Placebo Comparator group

Description:

Single ascending doses of ONO-2808 or placebo orally under fed conditions

Treatment:

Drug: Placebo

ONO-2808 Part B

Experimental group

Description:

Single dose of ONO-2808 or placebo in elderly female or elderly male healthy volunteers .

Treatment:

Drug: ONO-2808

ONO-2808 Placebo Part B

Placebo Comparator group

Description:

Single dose of ONO-2808 or placebo in elderly female or elderly male healthy volunteers

Treatment:

Drug: Placebo

ONO-2808 Part C

Experimental group

Description:

Multiple ascending doses of ONO-2808 or placebo orally

Treatment:

Drug: ONO-2808

ONO-2808 Placebo Part C

Placebo Comparator group

Description:

Multiple ascending doses of ONO-2808 or placebo orally

Treatment:

Drug: Placebo