Moderate to Severe Knee Pain Due to Osteoarthritis in subjects who are Inappropriate for Oral Non steroidal Anti inflammatory Therapy MedDRA version: 20.0 Level: PT Classification code 10031161 Term: Osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 20.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 20.0 Level: LLT Class
Conditions
Interventions
Product Name: PRX167700
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: PRX167700
Other descriptive name: PRX167700
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
Proximagen Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Participants who have symptomatic primary knee OA for at least 3 months prior to Screening. Participants must have had pain in the target knee for = 14 days per month in the 3 months preceding screening. 2. A diagnosis of knee OA based on American College of Rheumatology criteria with X ray confirmation (a Kellgren Lawrence X ray grade 2 or 3) in the target joint. The investigator is allowed to grade the x-ray if Kellgren-Lawrence grading is not provided in the original interpretation. One knee should be designated as the target joint. The pain in the target knee joint should exceed the pain experienced in other joints (including the contralateral knee joint and/or ipsilateral hip joint) and pain experienced from any concomitant medical condition. 3. Participants must be deemed inappropriate for oral NSAID therapy by their physician. Acceptable reasons for considering a participant inappropriate for oral NSAIDs include, but are not limited to, history of GI bleeding or GI intolerance of oral NSAIDs despite proton pump inhibitor treatment; inflammatory bowel disease; diverticular disease;hepatic or mild renal dysfunction; anticoagulation; presence of cardiovascular risk factors or disease; history of increased blood pressure with oral NSAID use; or asthma. 4. A moderate to severe pain score of = 8 and = 16 in the target knee joint evaluated by the WOMAC Pain Score at the Screening Visit (Visit 1), start of the single blind Placebo Run in (Visit 2), and at Baseline (Visit 3, Day 0). 5. The same or worse pain at Baseline (Visit 3, Day 0) compared to their WOMAC Pain Score at the start of the single blind Placebo Run in (Visit 2). 6. Body Mass Index (BMI) between 18 and 40 kg/m2, inclusive. 7. Male or female participants between 50 and 75 years of age, inclusive. 8. Female participants are eligible to participate in the study if they meet one of the following criteria: a.They are not of child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is postmenopausal as defined in Appendix 5) b.They are of child bearing potential, are not pregnant or lactating, are sexually active, and have a negative pregnancy test at Screening (Visit 1, serum test from central lab), Visit 2 (urine dipstick method in the clinic), and Baseline (Visit 3, urine dipstick method in the clinic). WOCBP who are sexually active must agree to use a highly effective contraception method during the study. A highly effective contraception method is defined as: i.Established use of oral, injected or implanted hormonal methods of contraception. ii.Placement of an intrauterine device (IUD) or intrauterine system (IUS). iii.Sole male partner is vasectomized. iv.Bilateral tubal occlusion. c.They are of childbearing potential, are not pregnant or lactating, are sexually abstinent, and have a negative pregnancy test at Screening (Visit 1, serum test from central lab), Visit 2 (urine dipstick method in the clinic), and Baseline (Visit 3, urine dipstick method in the clinic). WOCBP who are sexually abstinent at the start of the study must agree to remain abstinent for the duration of the study. 9. 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. 10. Participants who have been on a stable dose of analgesic therapy with agents other than the following for 30 days prior to screening:
Exclusion criteria
Exclusion criteria: 1. Causes of secondary knee arthritis, including septic arthritis, autoimmune joint disease, crystalline diseases, gout, articular fracture, and inherited disorders. 2. Pain relating to the target joint that has characteristics of neuropathic pain (eg, shooting or burning pain, pins and needles, allodynia and reflex sympathetic dystrophy). 3. Disease of the spine or of lower extremity joints (other than OA) which contribute to the pain the target joint. 4. Lower extremity surgery (including arthroscopy) within 6 months prior to Screening (Visit 1) or scheduled for surgery of any kind during the study. 5. Significant injury to the target joint within 12 months prior to Screening (Visit 1). 6. Use of a handicap assistance device (ie, cane, walker) > 50% of the time. 7. Active autoimmune disease or conditions requiring chronic immunosuppressive therapy, including as rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, organ transplant recipient. 8. Participants with epilepsy, those with a history of seizures (with the exception of febrile childhood seizures) and participants with a recognized risk for seizure. 9. Drug or alcohol abuse or dependence in the past 10 years. 10. Participants at risk of suicide in the assessment of the investigator, including those who disclose any suicidal behavior or suicide attempt in the year prior to screening. 11. Participants who suffer from emotional disturbance or depression as judged by the investigator at screening. 12. Known history of hypersensitivity or intolerance to paracetamol, tramadol or opioids, or a history of anaphylactic reactions to codeine or other opioids. 13. Participants at risk of respiratory depression, or any other situation where opioids are contraindicated. 14. Clinically significant illness other than OA within 3 months prior to Screening (Visit 1) which might interfere with the conduct of the trial. 15. History of malignancy within past 5 years (except for basal cell carcinoma or carcinoma in situ of the cervix treated with curative intent). 16. A personal or family history of long QTc syndrome, sudden cardiac death or known mutations of the Human Ether à go go Related Gene (hERG) channel or any other significant cardiovascular disease. 17. Poorly controlled hypertension at Screening (Visit 1), defined as systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg after 5 minutes rest in the supine position. 18. Presence of congestive heart failure (New York Heart Association Functional Classification, Class III-IV, inclusive). 19. Substantial renal dysfunction, defined as creatinine clearance < 60 mL/min; calculated by the Cockroft Gault method. 20. Clinically significant known infections including human immunodeficiency virus (HIV) infection. 21.Chronic liver disease. 22.Pregnant or breastfeeding. 23.Participants with any active medical condition or previous major abdominal surgery or procedure that might, in the investigator’s opinion, have a significant effect on drug absorption, distribution, metabolism, or excretion. 24.Participants who have failed prior therapy with oral NSAIDs due to lack of efficacy. 25.Use of tramadol at doses greater than 150 mg/day or other opioid analgesics at any dose for more than 4 days a week in the 30 days preceding screening (Visit 1). 26.Use of moderate or strong CYP3A4 or CYP2D6 inhibitors within 5 half lives prior to Visit 3. 27. Need for concomitant use of seroton
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of 6 weeks of PRX167700 treatment, as monotherapy, on the WOMAC Pain Score in participants with moderate to severe knee pain due to OA who are inappropriate for oral NSAID therapy;Secondary Objective: To assess the safety of 6 weeks of PRX167700 treatment. To assess additional measures of efficacy of PRX167700 treatment, versus placebo, at Day 42.;Timepoint(s) of evaluation of this end point: at every visit;Primary end point(s): To assess the effect of 6 weeks of PRX167700 treatment, as monotherapy, on the WOMAC Pain Score in participants with moderate to severe knee pain due to OA who are inappropriate for oral NSAID therapy, assessed by WOMAC Pain Score change from Baseline (Day 0) to End of Treatment (Day 42) in participants treated with PRX167700 versus placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence and severity of treatment emergent adverse events (TEAEs) throughout the dosing period • Incidence of TEAEs leading to withdrawal • Change in physical examination findings at each visit • Incidence of clinically significant changes on triplicate 12 lead electrocardiograms (ECGs) at each visit • Incidence and severity of treatment emergent changes in laboratory values at each visit • Change from Baseline in vital signs at each visit • Change from Baseline to Day 42 in the WOMAC Total Score • Change from Baseline to Day 42 in the WOMAC Stiffness Score • Change from Baseline to Day 42 in the WOMAC Function Score • Change from Baseline to Day 42 in the Patient Global Assessment (PGA) • Clinical Global Impression of Change (CGI C) at Day 42 • Proportion of participants with a response at Day 42 as defined by the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trial Response Criteria Initiative (OMERACT OARSI) Response Criteria • Proportion of participants with a reduction in the WOMAC Pain Score of = 50% at Day 42 • Withdrawal for lack of efficacy;Timepoint(s) of evaluation of this end point: at every visit | — |
Countries
Australia, New Zealand, United Kingdom
Outcome results
None listed