Osteoarthritis of the knee MedDRA version: 16.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: PRX167700
Product Code: PRX167700
Pharmaceutical Form: Capsule
INN or Proposed INN: PRX167700
Current Sponsor code: PRX167700
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Proximagen Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study inclusion criteria are: 1. Male or female subjects aged between 45 and 75 years inclusive. Female subjects are eligible to participate in the study if they are not of child-bearing potential or, if of child-bearing potential, are not pregnant or lactating; agree to use an acceptable method of contraception during the study. Female subjects should have a negative pregnancy test at Screening and Visit 2. 2. Body Mass Index (BMI) between 20 and 35 kg/m2, inclusive. 3. Symptomatic primary OA of the knee for at least 3 months prior to Screening according to the American College of Rheumatology (ACR) criteria. 4. 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. 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. ACR Clinical and radiographic diagnostic criteria consist of knee pain plus osteophytes, plus at least 1 of the following 3 criteria: i. Age >50 years ii. Morning stiffness =65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: 1. Secondary causes of arthritis of the knee, including septic arthritis, inflammatory joint disease, crystalline diseases, articular fracture, and inherited disorders. 2. Disease of the spine or of lower extremity joints (other than OA) which may affect the assessment of pain in the target knee joint. 3. Pain relating to target knee joint that has characteristics of neuropathic pain (e.g. shooting or burning pain, pins and needles, allodynia). 4. Has had lower extremity surgery (including arthroscopy) within 6 months prior to Screening or scheduled for surgery of any kind during the study. 5. Significant injury to the target knee joint within 12 months prior to Screening. 6. Known history of hypersensitivity or intolerance to paracetamol or lactose. 7. Corticosteroid injections before Screening: i. Intra-articular into the target knee joint within 3 months ii. Intra-articular into any site other than the target knee joint within 1 month iii. Intra-muscular within 3 months 8. Oral corticosteroids within 1 month of Screening. 9. Other therapeutic injections into the target knee joint within previous 3 months. 10. Use of any anti-inflammatory biological therapy within 12 months or methotrexate within 1 month prior to Visit 2. 11. Start or change in dosing regimen of other therapies for OA within 3 months of Screening. 12. Start or change in an established physiotherapy programme within 2 weeks of Screening or during the course of the study. An established physiotherapy program may be continued throughout the study period if unchanged in frequency and intensity. 13. Any clinical or biological abnormality found at screening (other than those related to OA) which, in the opinion of the investigator, is clinically significant and would preclude safe participation in this study (e.g. current malignancy, human immunodeficiency virus (HIV) infection, significant mental illness). 14. Clinically significant illness other than OA within 3 months prior to Screening. 15. History of malignancy within past 5 years (except for basal cell carcinoma or carcinoma-in-situ of the cervix treated with curative intent). Subjects with a history of melanoma, leukaemia, lymphoma, or myeloproliferative disease are ineligible for the study regardless of the time since treatment. 16. QTc =450 msec or, for subjects with bundle branch block, QTc >480 msec. 17. Uncontrolled hypertension at Screening: systolic blood pressure (SBP) >160 mmHg and/or sitting diastolic blood pressure (DBP) >90 mmHg. Hypertension controlled by medications is acceptable, as long as stable for at least one month prior to Screening. 18. Presence of congestive heart failure (New York Heart Association [NYHA] functional class II-IV). 19. Bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 times the upper limit of normal (ULN) or two or more of bilirubin, ALT or AST above the ULN at Screening. 20. Chronic Hepatitis B or C, as evidenced by positive Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody at Screening. 21. History of chronic alcoholic liver disease, drug or alcohol dependence. 22. Renal dysfunction at Screening, defined as estimated glomerular filtration rate <30 ml/min. 23. Use of potent inducers or inhibitors of CYP3A4 or inhibitors of CYP2D6 within 48 hours or 5 half-lives prior to Visit 2. 24. Receipt of an investigational product within 30 days or 5 half-lives or twice th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of PRX167700 treatment on Pain Intensity after walking and at rest in subjects with moderate to severe pain caused by osteoarthritis (OA) of the knee.;Secondary Objective: To assess the safety of PRX167700 over a 15 day dosing period. To investigate the pharmacokinetics of PRX167700 in male and female subjects with OA. To investigate the inhibition of plasma semicarbazide-sensitive amine oxidase (SSAO) activity by PRX167700. ;Primary end point(s): The primary endpoint is pain at rest and after walking 100 m on a flat course, measured using the 11-point numerical rating scale (NRS).;Timepoint(s) of evaluation of this end point: Study days 0, 1, 3, 7 and 14. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: WOMAC total score and subscales; Patient Global Impression of Change, time to complete walks, serum CRP levels, and rescue medication use. Safety: Safety and tolerability will be evaluated by assessing adverse events (AEs), clinical laboratory data, physical examinations, vital signs, and electrocardiograms (ECGs). Pharmacokinetics: The plasma concentration-time profile and pharmacokinetics (PK) parameters of PRX167700 will be determined from plasma samples collected on Day 15 (Visit 7) and from the single plasma sample collected at the end of each visit. Plasma concentration-time profiles and PK parameters, including (but not limited to) Cmax, tmax, area under the plasma concentration vs. time curve from time zero over the dosing interval to 6 hours post-dose (AUC0 tau), AUC0 8, and, if possible, t½.will be determined. Pharmacodynamics: The inhibition of plasma SSAO activity will be determined and the relationship between plasma drug concentrations, SSAO activity and clinical effects of PRX167700 will be investigated, as data permit. ;Timepoint(s) of evaluation of this end point: Study days 0, 1, 3, 7, 14 and 15. | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Information
Proximagen Limited
Outcome results
None listed