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

Phase 1

Completed

• Conditions: Osteoarthritis
• Interventions: Drug: ONO-4474 Part A1; Drug: ONO-4474 Part A2; Drug: Placebo Part A2; Drug: Placebo Part B; Drug: Placebo Part A1; Drug: Placebo Part C; Drug: ONO-4474 Part B; Drug: ONO-4474 Part D; Drug: Placebo Part D; Drug: ONO-4474 Part C

• Registration Number: NCT02454387
• Lead Sponsor: Ono Pharmaceutical Co. Ltd

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2015-04-29
• Study Start: 2015-05
• Study First Submitted QC: 2015-05-22
• Study First Posted: 2015-05-27
• Status Verified: 2016-01
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Last Update Submitted: 2016-06-29
• Last Update Posted: 2016-06-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

1. 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)
2. Subjects with a body mass index of 18.0-30.0 kg/m2 inclusive

Exclusion Criteria

1. Subjects who have a clinically relevant history or presence of any clinically significant disease or disorder
2. Current smokers or those that have smoked or used nicotine products within 6 months of the Screening visit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Experimental: ONO-4474 Part A1	ONO-4474 Part A1	Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Part A2	ONO-4474 Part A2	Single doses (2 periods) of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Placebo Part A2	Placebo Part A2	Single doses (2 periods) of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Placebo Part B	Placebo Part B	Multiple ascending doses of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Placebo Part A1	Placebo Part A1	Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Placebo Part C	Placebo Part C	NGF hyperalgesia and single or multiple doses of ONO-4474, randomized 1 active: 1 placebo in cross over design
Experimental: ONO-4474 Part B	ONO-4474 Part B	Multiple ascending doses of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Part D	ONO-4474 Part D	Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Placebo Part D	Placebo Part D	Single doses of ONO-4474 or placebo, randomized 3 active: 1 placebo
Experimental: ONO-4474 Part C	ONO-4474 Part C	NGF hyperalgesia and single or multiple doses of ONO-4474, randomized 1 active: 1 placebo in cross over design

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of ONO-4474 across ascending single and multiple doses using number of adverse events	Up to Day 28

Secondary Outcome Measures

Name	Time	Method
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.	3hr and 24hr after NGF injection	Pressure algometry at site of NGF injection (anterior tibialis)

Trial Locations

Locations (2)

Aalborg Clinical Site; 🇩🇰 Aalborg, Denmark

Nottingham Clinical SIte; 🇬🇧 Nottingham, United Kingdom