A Phase 1 Study of ONO-2020 in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this FIH study is to evaluate the safety, tolerability and pharmacokinetics of ONO-2020 in healthy adult participants. This FIH study consists of five parts (Parts A-E) to study single or multiple doses of ONO-2020 in healthy participants, including elderly and Japanese participants, as well as the food effect on the PK of ONO-2020. These data will support the clinical development program and help inform dose selection in future studies.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Five-part Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of ONO-2020 in Healthy Participants

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ONO-2020
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 55 years of age (Parts A, B, C, and E) or ≥65 years of age (Part D) inclusive at the time of informed consent. Male and female participants of non-Japanese ethnicity (Parts A, B, C, and D) or of Japanese ethnicity (Part E). 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 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. Agree to use an effective method of contraception. Able and willing to give informed consent after reading the information and consent form and after having the opportunity to discuss the study with the Investigator or designee. Estimated creatinine clearance (CrCL, Cockcroft-Gault equation) ≥90 mL/min at Screening. In Part D only, an estimated ≥60 mL/min at Screening. Fully vaccinated for SARS-CoV-2 (received primary series of COVID-19 vaccine) prior to Screening. Exclusion Criteria: Mentally or legally incapacitated or has 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 or disease that in the opinion of the Investigator or Sponsor Medical Monitor might confound the results of the study or pose an additional risk to the participant by their participation in the study. hypersensitivity or idiosyncratic reaction to the study interventions, excipients or related compounds, or severe food allergies. alcoholism or drug/chemical/substance abuse within the past 2 years prior to the first dosing. Use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements, including St. John's Wort, within 14 days or five half-lives (whichever is longer) of first dosing and throughout the study. Use of any drugs known to be significant inducers or inhibitors of cytochrome P450 (CYP) enzymes and/or drug transporter substrates for 28 days prior to the first dosing and throughout the study. Participation in another clinical study within 120 days (or five half-lives of the study intervention, whichever is longer) prior to the first dosing. Liver function test values are in the abnormal range before inclusion. Positive urine drug, alcohol, or cotinine results at Screening or check in. Positive results at Screening for active viral infection that include HIV, HBV, HCV, and SARS-CoV-2. Seated resting blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at Screening. Seated resting pulse rate is lower than 40 beats per minute (bpm) or higher than 100 bpm at Screening. Clinically significant history or presence of ECG findings. The participant is a current smoker or has smoked within 3 months of Screening or has a positive urine cotinine at Screening or admission. Female who is pregnant or lactating. Donation of blood or significant blood loss of 400 mL or more within 90 days prior to the first dosing, or blood donation of 200 mL or more within 30 days prior to the first dosing, or blood plasma or platelet donation within 14 days prior to the first dosing, or blood transfusion within 90 days prior to the first dosing. Participants who, in the opinion of the Investigator, are considered unsuitable for any other reason. Exclusion criteria, applicable to all participants taking part in the food effect Cohort in Part A: Participants who are vegetarian or vegan or not willing to eat a high-fat breakfast. Exclusion criteria, applicable to all participants undergoing lumbar puncture for CSF collection (Part C): History of significant back pain, significant kyphosis, and or scoliosis or other spinal column deformities. History of poor venous access. History of hypersensitivity for local anesthetics (Lidocaine). History or evidence or fundoscopic findings suggestive of raised intracranial pressure. History or evidence of laboratory abnormalities for coagulation parameters or the use of medications that may increase the risk of bleeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Cohort A1 ONO-2020 or Placebo - fasted<br>Single ascending doses of ONO-2020 orally under fasted conditions | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part A: Cohort A2 ONO-2020 or Placebo - fasted and fed<br>Single ascending doses of ONO-2020 orally under fasted and fed conditions | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part A: Cohort A3 ONO-2020 or Placebo - fasted<br>Single ascending doses of ONO-2020 orally under fasted conditions | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part A: Cohort A4 ONO-2020 or Placebo - fasted and fed<br>Single ascending doses of ONO-2020 orally under fasted and fed conditions | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part A: Cohort A5 ONO-2020 or Placebo - fasted<br>Single ascending doses of ONO-2020 orally under fasted conditions | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part A: Cohort A6 ONO-2020 or Placebo - fasted<br>Single ascending doses of ONO-2020 orally under fasted conditions | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part B: Cohort B1 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part B: Cohort B2 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part B: Cohort B3 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part B: Cohort B4 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part B: Cohort B5 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part C: Cohort C1 ONO-2020<br>Single dose of ONO-2020 orally for CSF sampling | Drug: ONO-2020<br>* ONO-2020 tablets<br>|
| Experimental: Part C: Cohort C2 ONO-2020<br>Single dose of ONO-2020 orally for CSF sampling | Drug: ONO-2020<br>* ONO-2020 tablets<br>|
| Experimental: Part D: Cohort D1 ONO-2020 or Placebo<br>Single dose of ONO-2020 orally in elderly healthy volunteers | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part E: Cohort E1 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days in Japanese healthy volunteers | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|
| Experimental: Part E: Cohort E2 ONO-2020 or Placebo<br>Multiple ascending doses of ONO-2020 orally for 14 days in Japanese healthy volunteers | Drug: ONO-2020<br>* ONO-2020 tablets<br>Drug: Placebo<br>* Placebo tablets matching ONO-2020 tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity, and type of treatment emergent adverse events (TEAEs) | Incidence of TEAEs will be summarized overall, and by study part and dose group using frequency and percentage. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Vital signs (blood pressure) | Observed values and change from baseline results will be summarized by analysis time point, and summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Vital signs (pulse rate) | Observed values and change from baseline results will be summarized by analysis time point, and summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Vital signs (body temperature) | Observed values and change from baseline results will be summarized by analysis time point, and summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Vital signs (respiratory rate) | Observed values and change from baseline results will be summarized by analysis time point, and summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| 12-lead electrocardiograms (ECGs) parameters, such as but not limited to heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF) | The number and percentage of subjects with normal, abnormal not clinically significant and abnormal clinically significant of ECG results will be tabulated at each time point. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Clinically significant abnormal telemetry electrocardiograms (ECGs) | The number and percentage of subjects with normal, abnormal not clinically significant and abnormal clinically significant of telemetry ECGs results will be tabulated at each time point. | Part A and D: Day 1 | 
| Clinically significant abnormal physical examination findings | The number and percentage of subjects with normal, abnormal not clinically significant and abnormal clinically significant of physical examination results will be tabulated at each time point. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Clinical laboratory abnormalities (hematology, clinical chemistry, coagulation, and urinalysis) | The number and percentage of subjects with abnormal laboratory results at any time during the study will be tabulated. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Ophthalmologic examination findings (pupil size and pupillary light reflex) | The number and percentage of subjects with miosis will be summarized by laterality at each time point. | Part A, C and D: From Day 1 up to Day 7, Part B and E: From Day 1 up to Day 21 | 
| Clinically abnormal findings in Mini-International Neuropsychiatric Interview Screen (M.I.N.I.-Screen) | Responses to the M.I.N.I.-Screen will be listed. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 
| Clinically abnormal findings in Columbia Suicide Severity Rating Scale (C-SSRS) | Responses to the suicidality assessment scale (C-SSRS) will be listed. | Part A, C and D: From screening up to Day 7, Part B and E: From screening up to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (Cmax in plasma) |  | Part A, C and D: Day 1 through Day 4, Part B and E: Day 1 through Day 19 | 
| Pharmacokinetics (Tmax in plasma) |  | Part A, C and D: Day 1 through Day 4, Part B and E: Day 1 through Day 19 | 
| Pharmacokinetics (AUClast in plasma) |  | Part A, C and D: Day 1 through Day 4, Part B and E: Day 1 through Day 19 | 
| Pharmacokinetics (AUCinf in plasma) |  | Part A, C and D: Day 1 through Day 4, Part B and E: Day 1 through Day 19 | 
| Pharmacokinetics (T1/2 in plasma) |  | Part A, C and D: Day 1 through Day 4, Part B and E: Day 1 through Day 19 | 
| Pharmacokinetics (CL/F in plasma) |  | Part A, C and D: Day 1 through Day 4, Part B and E: Day 1 through Day 19 | 
| Pharmacokinetics (Aet in urine) |  | Part A and D: Day 1 through Day 4 | 
| Pharmacokinetics (fe/F in urine) |  | Part A and D: Day 1 through Day 4 | 
| Pharmacokinetics (CLR in urine) |  | Part A and D: Day 1 through Day 4 | 
| Pharmacokinetics (Ctrough in plasma) |  | Part B and E: Day 2 through Day 13 | 
| Pharmacokinetics (ONO-2020 concentration in CSF) |  | Part C: Day 2 |