An Exploratory Study of PRX167700 in Patients With Knee Osteoarthritis

A Double-Blind, Randomised, Exploratory Study to Investigate the Safety, Efficacy and Pharmacokinetics of PRX167700 in Subjects With Knee Osteoarthritis.

This is an exploratory study to evaluate a new anti-inflammatory drug, PRX167700, in subjects with painful osteoarthritis of the knee.

The purpose of this study is to investigate if PRX167700 improves the pain from osteoarthritis of the knee, and to assess its safety and tolerability. The study will also investigate PRX167700 pharmacokinetics.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Placebo; Drug: PRX167700

Detailed Description

Up to 74 subjects will receive either PRX167700 or placebo (a dummy treatment) for 15 days. Subjects will need to stop taking their usual pain reliever medicines for at least 7 days before starting treatment to induce a 'flare' in osteoarthritis symptoms (but they will be allowed to continue to use paracetamol for immediate pain relief as needed throughout the trial). The effect of PRX167700 or placebo on knee pain will be assessed before and after exercise on Days 1, 3, 7 and 14. On Day 15, blood samples will be collected to measure levels of PRX167700 and assess its activity.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • Proximagen Investigational Site
  • Lancashire, United Kingdom
    • Proximagen Investigational Site
  • Liverpool, United Kingdom
    • Proximagen Investigational Site
  • Manchester, United Kingdom
    • Proximagen Investigational Site
  • Reading, United Kingdom
    • Proximagen Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body Mass Index (BMI) between 20 and 35 kg/m2, inclusive.
• Symptomatic primary OA of the knee for at least 3 months prior to Screening according to the American College of Rheumatology (ACR) criteria.
• Diagnosis of OA of the knee based on ACR criteria with X-ray confirmation (a Kellgren-Lawrence X-ray grade of ≥2) in the target knee joint.
• Use of analgesics for the treatment of knee OA for at least 4 out of 7 days in each of the 4 weeks preceding the Screening visit.
• Willing and able to discontinue all current analgesic therapy, including over the counter (OTC) pain medications and topical analgesics for OA pain, for a period beginning at Screening and continuing for the entire duration of the study.
• Able to walk 100 metres on a flat course without rest and unaided.
• A self-rated Pain Intensity score in the target knee joint of between 3 and 8, inclusive, immediately after a timed 100 metres walk on a flat course.
• Able to provide written informed consent to participate in the study and, in the opinion of the investigator, able to read, comprehend and record information as required by the protocol.

Exclusion Criteria:

• Secondary causes of arthritis of the knee, disease of the spine or of lower extremity joints (other than OA), knee pain characteristic of neuropathic pain.
• Lower extremity surgery (including arthroscopy) within 6 months prior to Screening or scheduled for surgery of any kind during the study.
• Significant injury to the target knee joint within 12 months prior to Screening.
• Known history of hypersensitivity or intolerance to paracetamol or lactose.
• Oral corticosteroids within 1 month of Screening
• Therapeutic injections into the target knee joint within previous 3 months. Intra-articular corticosteroid injections into any other site within 1 month or intra-muscular corticosteroid injections within 3 months.
• Start or change in dosing regimen of other therapies for OA within 3 months of Screening.
• Start or change in an established physiotherapy programme within 2 weeks of Screening (Visit 1) or during the course of the study. An established physiotherapy program may be continued throughout the study period if unchanged in frequency and intensity.
• Any significant clinical or biological abnormality (other than those related to OA) which would preclude safe participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Oral capsule
EXPERIMENTAL: PRX167700	Drug: PRX167700; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity	Measured at rest and after exercise at 1, 2 and 3 hours post-dose. Measured using 11-point numerical rating scale (NRS)ranging from 0 to 10 where 0 represents no pain and 10 represents the worst possible pain	Study Days 0 [Baseline], 1, 3, 7 and 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy:	Western Ontario and McMaster Universities (WOMAC)Questionnaire total score and subscales;; Patient Global Impression of Change;; Time to complete exercise;; Serum C-reactive protein levels;; Rescue medication use.	Study Days 0 [Baseline], 1, 3, 7 and 14
Safety	Safety and tolerability will be evaluated by assessing adverse events (AEs), clinical laboratory data, physical examinations, vital signs, and electrocardiograms (ECGs).	15 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Plasma concentration-time profiles and pharmacokinetic parameters, including (but not limited to) Cmax, tmax, area under the plasma concentration vs. time curve from time zero over the dosing interval, area under the concentration-time curve over the dose interval and to infinity, and, if possible, t½.will be determined.	Day 15
Pharmacodynamics	Biomarker activity following dosing	Day 15

Collaborators and Investigators

• Sponsor: Proximagen Limited
• Investigators: Study Director: Medical Monitor, Proximagen Limited

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 13, 2013
• First Posted (ESTIMATE): September 18, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 26, 2015
• Last Update Submitted That Met QC Criteria: August 25, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Osteoarthritis; PRX167700
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 167700-002CL