A First in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of ONO-2808-01 in Healthy Participants
- Registration Number
- NCT04578028
- Lead Sponsor
- Ono Pharmaceutical Co. Ltd
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 94
Not provided
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Mentally or legally incapacitated or with significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
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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.
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Liver chemistry values above the upper limit of normal (ULN) at Screening or admission.
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Sensitivity to the study drug.
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Female who is pregnant or lactating or of childbearing potential.
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History or presence of alcoholism or drug/chemical/substance abuse.
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Evidence of poor venous access as assessed by PI.
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Use of any medication which may affect ONO-2808 pharmacokinetics or pharmacodynamics
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Current smoker or has smoked (including use of tobacco and/or nicotine-containing products) in the previous 3 months
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Positive urine drugs of abuse, cotinine or alcohol results at Screening or admission.
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Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
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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).
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Supine resting pulse rate lower than 40 beats per minute (bpm) or higher than 100 bpm.
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Clinically significant history or presence of ECG findings at screening.
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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.
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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.
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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.
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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.
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Objection by PI
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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):
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History of significant back pain, significant kyphosis and or scoliosis or other spinal column deformities.
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History or evidence of fundoscopy suggestive of raised intracranial pressure.
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History or presence of any allergy or contraindication to the local anaesthetic required for participants undergoing lumbar puncture.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ONO-2808 Placebo Part B Placebo Single dose of ONO-2808 or placebo in elderly female or elderly male healthy volunteers ONO-2808 Placebo Part A - Fed Placebo Single ascending doses of ONO-2808 or placebo orally under fed conditions ONO-2808 Placebo Part A- Fasted Placebo Single ascending doses of ONO-2808 or placebo orally under fasted conditions ONO-2808 Part C ONO-2808 Multiple ascending doses of ONO-2808 or placebo orally ONO-2808 Placebo Part C Placebo Multiple ascending doses of ONO-2808 or placebo orally ONO-2808 Part A - Fasted ONO-2808 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. ONO-2808 Part A - Fed ONO-2808 Single ascending doses of ONO-2808 or placebo orally under fed conditions ONO-2808 Part B ONO-2808 Single dose of ONO-2808 or placebo in elderly female or elderly male healthy volunteers .
- Primary Outcome Measures
Name Time Method Treatment emergent adverse events (TEAEs) by severity. Part A and B: up to day 7; Part C: up to 17 days. 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.
ECG parameters Part A and B: up to day 7; Part C: up to 17 days. Number of participants with ECG abnormalities
Serious adverse events (SAEs) Part A and B: up to day 7; Part C: up to 17 days. 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.
Vital signs Part A and B: up to day 7; Part C: up to 17 days 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
Physical examination Part A and B: up to day 7; Part C: up to 17 days Number of participants with physical examination abnormalities
Neurological examination Part A and B: up to day 7; Part C: up to 17 days. Number of participants with neurological examination abnormalities
Clinical laboratory tests Part A and B: up to day 7; Part C: up to 17 days Number of participants with clinical laboratory abnormalities (including haematology, clinical chemistry and urinalysis)
Number of participants with suicidal behaviour Part C: up to 17 days Treatment-emergent suicidal ideation and behaviour will be monitored by using the Columbia Suicide Severity Rating Scale (C-SSRS) and reported.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (AUClast) Part A & B: Day 1 through Day 7 Assessment of the area under the concentration-time curve of ONO-2808 to last measurable concentration
Pharmacokinetics (AUCinf) Part A & B: Day 1 through Day 7 Assessment of the area under the concentration-time curve of ONO-2808 extrapolated to infinite time in plasma
Pharmacokinetics (CL/F) Part A & B: Day 1 through Day 7 Assessment of the apparent clearance of ONO-2808 from plasma
Pharmacokinetics (Cmax) Part A & B: Day 1 through Day 7, Part C: Day 1 and 14 Assessment of the maximum observed plasma concentration of ONO-2808
Pharmacokinetics (Tmax) Part A & B: Day 1 through Day 7, Part C: Day 1 and 14 Assessment of the time to reach Tmax for ONO-2808
Pharmacokinetics (AUCtau) Part C: Day 1 and Day 14 Assessment of the area under the concentration-time curve of ONO-2808 during the dosing interval in plasma
Pharmacokinetics (Vz/F) Part A & B: Day 1 through Day 7 Assessment of the apparent volume of distribution of ONO-2808 during terminal elimination phase
Pharmacokinetics (Aetz) Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14 Assessment of the amount of ONO-2808 excreted in urine over the period of sample collection
Pharmacokinetics (CLR) Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14. Assessment of the renal clearance of ONO-2808 from plasma
Pharmacokinetics (T1/2) Part A & B: Day 1 through Day 7 Assessment of the terminal elimination half-time of ONO-2808 in plasma
Pharmacokinetics (Percentage fe) Part A & B: Day 1 through Day 5, Part C: Day 1, 8 & 14 Assessment of the cumulative percentage of orally administered ONO-2808 excreted into urine
Distribution of ONO-2808 to the brain in Part A Part A (in selected fasted cohorts): Day 1 and 2, Part C: Day 1 and Day 14 Assessment of ONO-2808 brain distribution by measuring drug concentration in the cerebro spinal fluid (CSF)
Trial Locations
- Locations (1)
Parexel International Early Phase Clinical Unit (EPCU)
🇬🇧London, United Kingdom