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

NCT04578028 | Completed Phase 1

• 2 other identifiers: ONO-2808-012019-004693-26
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurodegenerative Diseases

Keywords

Neurodegenerative Diseases

Outcome Measures

Primary Outcomes (8)

• Treatment emergent adverse events (TEAEs) by severity.

  Number of participants with TEAEs. An adverse event is any untoward medical occurrence in a participant who receive study drug without regard to possible causal relationship.

  Part A and B: up to day 7; Part C: up to 17 days.

• Serious adverse events (SAEs)

  Number of participants with SAEs. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged hospitalization, life-threatening experience or persistent disability.

  Part A and B: up to day 7; Part C: up to 17 days.

• Vital signs

  Summary statistics of vital signs and number of participants with clinically significant changes in vital signs including pulse/heart rate, respiratory rate, and blood pressure

  Part A and B: up to day 7; Part C: up to 17 days

• ECG parameters

  Number of participants with ECG abnormalities

  Part A and B: up to day 7; Part C: up to 17 days.

• Clinical laboratory tests

  Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis)

  Part A and B: up to day 7; Part C: up to 17 days

• Physical examination

  Number of participants with physical examination abnormalities

  Part A and B: up to day 7; Part C: up to 17 days

• Neurological examination

  Number of participants with neurological examination abnormalities

  Part A and B: up to day 7; Part C: up to 17 days.

• Number of participants with suicidal behaviour

  Treatment-emergent suicidal ideation and behaviour will be monitored by using the Columbia Suicide Severity Rating Scale (C-SSRS) and reported.

  Part C: up to 17 days

Secondary Outcomes (12)

• Pharmacokinetics (Cmax)

  Part A & B: Day 1 through Day 7, Part C: Day 1 and 14

• Pharmacokinetics (Tmax)

  Part A & B: Day 1 through Day 7, Part C: Day 1 and 14

• Pharmacokinetics (AUClast)

  Part A & B: Day 1 through Day 7

• Pharmacokinetics (AUCinf)

  Part A & B: Day 1 through Day 7

• Pharmacokinetics (AUCtau)

  Part C: Day 1 and Day 14

Study Arms (8)

ONO-2808 Part A - Fasted

EXPERIMENTAL

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.

Drug: ONO-2808

ONO-2808 Placebo Part A- Fasted

PLACEBO COMPARATOR

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

Drug: Placebo

ONO-2808 Part A - Fed

EXPERIMENTAL

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

Drug: ONO-2808

ONO-2808 Placebo Part A - Fed

PLACEBO COMPARATOR

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

Drug: Placebo

ONO-2808 Part B

EXPERIMENTAL

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

Drug: ONO-2808

ONO-2808 Placebo Part B

PLACEBO COMPARATOR

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

Drug: Placebo

ONO-2808 Part C

EXPERIMENTAL

Multiple ascending doses of ONO-2808 or placebo orally

Drug: ONO-2808

ONO-2808 Placebo Part C

PLACEBO COMPARATOR

Multiple ascending doses of ONO-2808 or placebo orally

Drug: Placebo

Interventions

ONO-2808 DRUG

Investigational drug

ONO-2808 Part A - Fasted; ONO-2808 Part A - Fed; ONO-2808 Part B; ONO-2808 Part C

Placebo DRUG

Placebo drug

ONO-2808 Placebo Part A - Fed; ONO-2808 Placebo Part A- Fasted; ONO-2808 Placebo Part B; ONO-2808 Placebo Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide fully informed written consent.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead
• Parexel: collaborator

Study Sites (1)

Parexel International Early Phase Clinical Unit (EPCU)

London, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Neurodegenerative Diseases

Condition Hierarchy (Ancestors)

Nervous System Diseases

Study Officials

• Pablo F Soto, MD,MSc, PhD

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study. A sentinel dosing approach will be used in the study at each new ascending dose level in Part A, B, and C. To maintain the blinded nature of the study, the sentinel participants will be randomised to drug or placebo in a 1:1 ratio.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: August 19, 2020
• Primary Completion: August 26, 2021
• Study Completion: October 7, 2021
• Last Updated: December 30, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)