Osteoarthritis of the knee MedDRA version: 9.1 Level: LLT Classification code 10031165 Term: Osteoarthritis knee
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria – general 1. Subject is male or female outpatient, = 40 years of age. A female is eligible to participate in this study if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, b. Child-bearing potential, has a negative pregnancy test and is not lactating at the Screening and Baseline/Randomisation Visits and agrees to satisfy one of the requirements listed in Appendix 1: Acceptable Methods of Contraception. 2. Subject is able and willing to give written informed consent 3. Subject is able to read, comprehend and record information required in the protocol e.g. complete assessments using an electronic device. Inclusion criteria – related to OA 1. Meets ACR clinical and radiographic criteria for classification of idiopathic (primary) osteoarthritis of the knee as defined by: knee pain and radiographic osteophytes and at least one of the following: i. Age > 50 years ii. Morning stiffness =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria – general: 1. Known history of hypersensitivity or intolerance to NSAIDs or aspirin, unless subject has subsequently taken at least two separate NSAIDs for at least 1 month without reaction. History of aspirin/NSAID-sensitive asthma, rhinitis, urticaria or nasal polyps. 2. Intolerance to paracetamol. 3. Any clinical or biological abnormality found at screening (other than those related to the disease under investigation) 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). 4. QTc =450msecs or QTc >480msecs for subjects with bundle branch block (based on a 12-lead ECG); single or average QTc value of triplicate ECGs, obtained over a brief recording period. This applies to QTc intervals measured either by Bazett’s or Fridericia’s formula (machine or manual over-read, male or female subjects). 5. Uncontrolled hypertension at screen SBP >160mmHg and/or sitting diastolic blood pressure DBP >90mmHg). Hypertension controlled by medications is acceptable, as long as stable for at least one month prior to screening (view protocol). 6. Presence of congestive heart failure (NYHA functional class II-IV) 7. History or presence of the following gastrointestinal disorders: a peptic ulceration b gastrointestinal bleeding Note: (view protocol) 8. Subjects with any one of creatinine, bilirubin, alanine aminotransferase (ALT) or aspartate aminotransfarase (AST) > 1.5 times the upper limit of normal (ULN) at screen are excluded. Subjects with two or more of bilirubin, ALT or AST above the ULN are excluded 9. Chronic Hepatitis B and C, as evidenced by positive Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody 10. History of chronic alcoholic liver disease 11. Renal dysfunction, defined as estimated glomerular filtration rate <30 ml/min (calculated by central laboratory from the 4-variable Modification of Diet in Renal Disease (MDRD) formula 12. Use of potent CYP3A4 inhibitors (please view protocol). 13. Use of methotrexate is prohibited. For other substrates for the organic anion transporting peptide (OATP1B1) (see protocol section 5.6.2.1 Prohibited medications) 14. Use of a combination of a diuretic with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). Please view protocol. 15. Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents (excluding low-dose aspirin) or a condition associated with decreased haemostasis 16. A history of clinically significant drug or alcohol abuse, as defined by Diagnostic and Statistical Manual of Mental Disorders, (please view protocol). 17. Participation in another investigational drug or device study during the 3 months prior to the Baseline/Randomisation Visit, (please view protocol). Exclusion criteria related to OA: 1. Secondary causes of arthritis of the knee, please view protocol. 2. Had lower extremity surgery (including arthroscopy) within 6 months prior to screening or scheduled for surgery of any kind during the study period 3. Significant prior injury to the index knee within 12 months prior to screen. 4. Use of lower extremity assistive devices other than a cane or knee brace (use of a ‘shoe lift’ is permitted) 5. Disease of the spine or other lower extremity joints of sufficient degree to affect the index knee. 6. Any other arthritic condition th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the clinical efficacy of GW842166 versus placebo in the treatment of pain associated with osteoarthritis of the knee.;Secondary Objective: • To evaluate the safety and tolerability of GW842166 administered orally to subjects with osteoarthritis of the knee. • To evaluate the dose response of GW842166 (incorporating 2 dose levels) and placebo in the primary efficacy endpoint. • To explore the clinical efficacy of GW842166 versus naproxen 500mg BID in the treatment of pain associated with osteoarthritis of the knee. • To evaluate the pharmacokinetic (PK) parameters of GW842166 in subjects with osteoarthritis of the knee. • To characterise the relationship between plasma concentrations and analgesic effect of GW842166 (PK-PD).;Primary end point(s): • Change from baseline to Day 28 LOCF in Western Ontario and McMasters Universities OA Index (WOMAC) pain subscale score. | — |
Countries
Denmark, Germany, Spain, Sweden
Outcome results
None listed