Clinical trial NCT04578028: A First in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of ONO-2808-01 in Healthy Participants
Official title: A Randomised, Double Blind, Placebo Controlled, Single Centre, Three-Part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of ONO-2808 in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neurodegenerative Diseases
Keywords: Neurodegenerative Diseases
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2020-10-08
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a single centre, three-part study conducted at a specialised Phase I centre to evaluate the safety, tolerability and pharmacokinetics of ONO-2808. This study consists of: Part A single ascending dose (including an assessment of potential food effects), Part B an assessment of age, and Part C multiple ascending dose. All parts of the study are conducted in healthy male and female (women of non-child bearing potential) participants. All parts of the study will have a 28-day screening period followed by admission to the clinical unit at least one day prior to dosing (Day -1) for baseline assessments. For all Parts of the study, a sentinel dosing approach is used to mitigate the overall safety risk with at least 1 day stagger to the rest of the cohort.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment emergent adverse events (TEAEs) by severity.
timeFrame: Part A and B: up to day 7; Part C: up to 17 days.
measure: Serious adverse events (SAEs)
timeFrame: Part A and B: up to day 7; Part C: up to 17 days.
measure: Vital signs
timeFrame: Part A and B: up to day 7; Part C: up to 17 days
measure: ECG parameters
timeFrame: Part A and B: up to day 7; Part C: up to 17 days.
measure: Clinical laboratory tests
timeFrame: Part A and B: up to day 7; Part C: up to 17 days
measure: Physical examination
timeFrame: Part A and B: up to day 7; Part C: up to 17 days
measure: Neurological examination
timeFrame: Part A and B: up to day 7; Part C: up to 17 days.
measure: Number of participants with suicidal behaviour
timeFrame: Part C: up to 17 days
Secondary outcomes:
measure: Pharmacokinetics (Cmax)
timeFrame: Part A & B: Day 1 through Day 7, Part C: Day 1 and 14
measure: Pharmacokinetics (Tmax)
timeFrame: Part A & B: Day 1 through Day 7, Part C: Day 1 and 14
measure: Pharmacokinetics (AUClast)
timeFrame: Part A & B: Day 1 through Day 7
measure: Pharmacokinetics (AUCinf)
timeFrame: Part A & B: Day 1 through Day 7
measure: Pharmacokinetics (AUCtau)
timeFrame: Part C: Day 1 and Day 14
measure: Pharmacokinetics (T1/2)
timeFrame: Part A & B: Day 1 through Day 7
measure: Pharmacokinetics (CL/F)
timeFrame: Part A & B: Day 1 through Day 7
measure: Pharmacokinetics (Vz/F)
timeFrame: Part A & B: Day 1 through Day 7
measure: Pharmacokinetics (Aetz)
timeFrame: Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14
measure: Pharmacokinetics (Percentage fe)
timeFrame: Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14
measure: Pharmacokinetics (CLR)
timeFrame: Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14.
measure: Distribution of ONO-2808 to the brain in Part A
timeFrame: Part A (in selected fasted cohorts): Day 1 and 2, Part C: Day 1 and Day 14
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Parexel International Early Phase Clinical Unit (EPCU)
Study officials:
affiliation: Parexel
name: Pablo F Soto, MD,MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References: