A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacology of ONO-4474 in Healthy Volunteers

Study Overview
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Brief Summary
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A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacology of ONO-4474 in healthy volunteers.

Detailed Description
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A Double-blind, Multi-centre, Single Dose, Single and Multiple Ascending Dose, Four-part, Randomised, Placebo-controlled Study in Healthy Adult and Elderly Subjects Exploring the Safety, Tolerability, Pharmacokinetics of ONO-4474 in Fed and Fasted Conditions, and Pharmacology of ONO-4474 in NGF-hyperalgesia.

Official Title
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A Double-blind, Single and Multiple Ascending Dose, Randomised, Placebo-controlled Study, in Healthy Adult and Elderly Subjects Exploring Safety, Tolerability, Pharmacokinetics of ONO-4474 and Pharmacology of ONO-4474 in NGF-hyperalgesia

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: ONO-4474 Part A1
* Drug: Placebo Part A1
* Drug: ONO-4474 Part A2
* Drug: Placebo Part A2
* Drug: ONO-4474 Part B
* Drug: Placebo Part B
* Drug: ONO-4474 Part C
* Drug: Placebo Part C
* Drug: ONO-4474 Part D
* Drug: Placebo Part D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 18-55 years inclusive (Parts A and C); healthy male and female subjects aged 18-55 years inclusive (Part B); healthy male and female subjects aged 65 and over (Part D) Subjects with a body mass index of 18.0-30.0 kg/m2 inclusive Exclusion Criteria: Subjects who have a clinically relevant history or presence of any clinically significant disease or disorder Current smokers or those that have smoked or used nicotine products within 6 months of the Screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: ONO-4474 Part A1<br>Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: ONO-4474 Part A1<br>* Healthy volunteers<br>* Other names: ONO-4474;|
| Placebo Comparator: Experimental: ONO-4474 Placebo Part A1<br>Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: Placebo Part A1<br>* Healthy volunteers<br>* Other names: Placebo;|
| Experimental: Experimental: ONO-4474 Part A2<br>Single doses (2 periods) of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: ONO-4474 Part A2<br>* Healthy volunteers<br>* Other names: ONO-4474;|
| Placebo Comparator: Experimental: ONO-4474 Placebo Part A2<br>Single doses (2 periods) of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: Placebo Part A2<br>* Healthy volunteers<br>* Other names: Placebo;|
| Experimental: Experimental: ONO-4474 Part B<br>Multiple ascending doses of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: ONO-4474 Part B<br>* Healthy volunteers<br>* Other names: ONO-4474;|
| Placebo Comparator: Experimental: ONO-4474 Placebo Part B<br>Multiple ascending doses of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: Placebo Part B<br>* Healthy volunteers<br>* Other names: Placebo;|
| Experimental: Experimental: ONO-4474 Part C<br>NGF hyperalgesia and single or multiple doses of ONO-4474, randomized 1 active: 1 placebo in cross over design | Drug: ONO-4474 Part C<br>* Healthy volunteers<br>* Other names: ONO-4474;|
| Placebo Comparator: Experimental: ONO-4474 Placebo Part C<br>NGF hyperalgesia and single or multiple doses of ONO-4474, randomized 1 active: 1 placebo in cross over design | Drug: Placebo Part C<br>* Healthy volunteers<br>* Other names: Placebo;|
| Experimental: Experimental: ONO-4474 Part D<br>Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: ONO-4474 Part D<br>* Healthy volunteers<br>* Other names: ONO-4474;|
| Placebo Comparator: Experimental: ONO-4474 Placebo Part D<br>Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo | Drug: Placebo Part D<br>* Healthy volunteers<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of ONO-4474 across ascending single and multiple doses using number of adverse events |  | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration of ONO-4474 (Cmax) |  | Day 1 and at Day 7 | 
| ONO-4474 Plasma Area Under the Curve from Time Zero to 24 hour after dosing (AUC24) |  | Day 1 and at Day 7 | 
| Time to Reach Maximum Observed Plasma concentration (Tmax) of ONO-4474 |  | Day 1 and at Day 7 | 
| Plasma Decay half life (T1/2) of ONO-4474 |  | Day 1 and at Day 7 | 
| Part C only - Evaluation of ONO-4474 vs. placebo on walking soreness using a Likert scale |  | 3hr and 24hr after NGF injection | 
| Part C only: Assessment of pharmacology of ONO-4474 using change in pressure pain threshold after NGF injection. | Pressure algometry at site of NGF injection (anterior tibialis) | 3hr and 24hr after NGF injection |