Testing APPA-1 in Healthy Subjects and Osteoarthritis Patients

NCT07429565 | Completed Phase 1 DMC

• 1 other identifier: UoL001261
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

To determine the safety and tolerability of ascending single and multiple oral doses of APPA-1 in healthy subjects and osteoarthritis patients. To determine the single and multiple oral dose pharmacokinetics of APPA-1 constituents (paeonol/apocynin) in healthy subjects and osteoarthritis patients. To determine the effect of food on the single oral dose pharmacokinetics of APPA-1 constituents (paeonol/apocynin) in healthy subjects. To determine the effect of gender on the single oral dose pharmacokinetics of APPA-1 constituents (paeonol/apocynin) in healthy subjects. To determine the multiple oral dose pharmacodynamics of APPA-1 in osteoarthritis patients.

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Safety of APPA-1 - Adverse Events will be collected and classified into standard terminology using MedDRA coding.

  Adverse events will be collected from consent until 28 days after treatment ends.

  Part A: 67 days (groups A1,2,4 and 5) and 75 days group A3. Part B: 77 days

Secondary Outcomes (14)

• Effect of food on pharmacokinetics of APPA-1 constituents

  14 days.

• Effect of food on pharmacokinetics of APPA-1 constituents

  14 days.

• Effect of gender on pharmacokinetics of APPA-1 constituents (paeonol/apocynin) in healthy subjects

  14 days.

• Effect of gender on pharmacokinetics of APPA-1 constituents (paeonol/apocynin) in healthy subjects

  14 days.

• Pharmacokinetics of APPA-1 constituents - plasma concentrations of apocynin and paeonol

  14 days

Study Arms (2)

APPA-1

EXPERIMENTAL

PART A: 16 healthy volunteers, oral capsule(s). One dose, except for group A3 (two treatment periods) Group A1: 400 mg, APPA-1 capsule A2 - 800 mg, 2 capsules A3 - 1600 mg, capsules A4 - 3200 mg, 8 capsules A5 - TBC - females Dose levels may change following review of safety and PK data from previous dose levels. PART B: 9 osteoarthritis, one dose to be determined following Part A.

Drug: APPA-1

Placebo

PLACEBO COMPARATOR

PART A: 4 healthy volunteers, oral capsule(s). One dose, except for group A3 (two treatment periods) Group A1: 400 mg, APPA-1 capsule A2 - 800 mg, 2 capsules A3 - 1600 mg, capsules A4 - 3200 mg, 8 capsules A5 - TBC - females Dose levels may change following review of safety and PK data from previous dose levels. PART B: 3 osteoarthritis, one dose to be determined following Part A.

Drug: Placebo Oral Tablet

Interventions

APPA-1 DRUG

APPA is an acronym for the combination of apocynin (AP) and its isomer, paeonol (PA). It is an orally administered synthetic combination of two compounds: * 4'-hydroxy-3'-methoxy-acteophenone (apocynin\[acetovanillone\]); * 2'-hydroxy -4'-methoxy acetophenone (paeonol). The intention is that the two actives will be available as a fixed combination product. The proposed ratio is 7:2 (paeonol:apocynin).

APPA-1

Placebo Oral Tablet DRUG

Identical to IMP apart from active substance.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Groups A1 to A4 will be male subjects only, Group A5 will consist of female subjects only to assess potential gender effects.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PART A:
• Written informed consent
• Between 18 and 75 years of age, inclusive
• Of any ethnic origin
• Healthy male subjects (groups A1 to A4)
• Healthy female subjects (group A5)
• BMI between 18.0 to 35.0 kg/m2
• In good health as defined by medical history (including confirmation from GP), physical examination, vital signs assessment, 12 lead ECG and clinical laboratory evaluation.
• PART B:
• Written informed consent
• Between 18 and 75 years of age inclusive
• Of any ethnic origin
• Male or female subjects with a diagnosis of osteoarthritis fulfilling the American College of Rheumatology (ACR) criteria for diagnosis
• BMI between 18.0 to 35.0 kg/m2

You may not qualify if:

• PART A:
• Male subjects who do not agree, or whose partners of childbearing potential do not agree, to use appropriate contraception or to refrain from donating sperm from the time of dosing until 3 months after the last dose of study drug.
• Female subjects of childbearing potential not in agreement to use two highly effective methods of contraception, or to refrain from donating ova, from the time of screening until 28 days after the Follow Up Visit.
• Female subjects who are pregnant or currently lactating
• Donated blood in the 3 months prior to screening, plasma in the 7 days prior to screening, platelets in the 6 weeks prior to screening
• Consume more than 28 units of alcohol per week if male, or 21 units of alcohol per week if female or any significant history of alcohol / substance misuse as determined by the investigator
• Unwilling to abstain from vigorous exercise for 48 hours prior to any study visit
• Unwilling to abstain from alcohol for 48 hours prior to any study visit
• Tobacco smoking within 30 days of first dose, including use of e-cigarettes and not willing to abstain from smoking until after study involvement.
• Received any medication, including St John's Wort, known to chronically alter drug absorption or elimination within 30 days prior to first dose administration unless in the opinion of the investigator it will not interfere with study procedures or compromise safety.
• Received any prescribed systemic or topical medication within 14 days prior to the first dose administration (with the exception of the OCP)
• Received any non-prescribed systemic or topical medication, herbal remedy or vitamin / mineral supplementation within 14 days prior to the first dose administration (with the exception of paracetamol).
• Subjects who have any abnormality of vital signs prior to the first dose administration that, in the opinion of the investigator, would increase the risk of participating in the study
• Subjects who have any clinically significant abnormal physical examination finding
• Subjects who have any clinically significant 12 lead ECG abnormality that, in the opinion of the investigator, would increase the risk of participating in the study

Sponsors & Collaborators

• University of Liverpool: lead
• AKL Research and Development: collaborator

Study Sites (2)

Royal Liverpool University Hospitals NHS Foundation Trust

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

University of Liverpool

Liverpool, L69 7ZB, United Kingdom

Location

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Rob Prof Moots, FRCP

  Universiy of Liverpool

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The randomisation code list will be generated by the LCTU trial statistician with the software package STATA. The trial is partially-blinded. Study participants will be allocated to treatment via block randomisation. The block size used in the randomisation will be kept blinded during the conduct of the study. An independent randomisation expert at the University of Liverpool will execute the randomisation program. Part A, group A1 will be partially blind and placebo controlled. Part A, groups A2, A3, A4 and A5 and Part B will be double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during their conduct.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In Part A, in each of Groups A1 to A5, 1 subject will be randomly assigned to receive placebo. For Group A1 sentinel dosing will occur whereby two subjects (1 active and 1 placebo) will be dosed on one day and, providing no safety concerns arise, the remaining subjects will be dosed the following day. Subjects in Group A3 (food-effect arm) will be randomised to the same treatment in Treatment Periods 1 and 2. In Part B, one subject per group will be randomly assigned to receive placebo. As the primary outcome is the observation of dose limiting toxicity, no formal sample size calculations were performed. Instead, a typical phase I design was adopted which will enrol 20 healthy subjects in the single-ascending part (part A) and 12 patients with osteoarthritis in the multiple ascending part (Part B) of the study. Patient allocation will be performed as shown in the study design schema.

Study Record Dates

• First Submitted: January 22, 2018
• First Posted: February 24, 2026
• Study Start: April 9, 2018
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: February 24, 2026

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)