A double-blind, two-period, placebo controlled cross-over study of the effects of the CB2 agonist GW842166 on pain and sensitisation in patients with osteoarthritis.

• Conditions: Osteoarthritis; MedDRA version: 8.1Level: LLTClassification code 10023476Term: Knee osteoarthritis

• Registration Number: EUCTR2006-003602-26-GB
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-09
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

A patient will be eligible for inclusion in this study only if all of the following criteria apply:
1. Male or female patients, 50 to 80 years of age.
2. 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 (more than 1 year since last menstrual cycle), had a tubal ligation or is surgical sterilised); or, b) child-bearing potential, has a negative pregnancy test (urine) at screen and baseline, and agrees to one of the following:
• Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject; or
• Implants of levonorgestral; or
• Injectable progestogen; or
• Oral contraception (combined or progestogen only); or
• Any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year; or
• Barrier method only if used with any of the above acceptable methods.
3. A diagnosis of primary osteoarthritis of the knee at least 3 months in symptom duration prior to screen. For patients with OA in both knees, an index knee will be specified.
4. Meets American College of Rheumatology (ACR) criteria for symptomatic osteoarthritis of the knee as defined by knee pain and radiographic evidence of osteophytes (Altman 1986)
5. Global functional status I, II or III according to ACR classification.
6. Patient has a minimum of 40mm on the 100mm VAS (WOMAC pain subscale) at baseline / randomisation. In addition, baseline pain must be stable for at least 72 hours prior to randomisation based on patient’s assessment.
7. Patient has a maximum of 80mm on the 100mm VAS (WOMAC pain subscale) at screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria – general:
1. Intolerance of paracetamol.
2. 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).
3. QTc =450msecs based on a 12-lead ECG obtained over a brief recording period. This applies to QTc intervals measured either by Bazzett’s or Fridericia’s formula
(machine or manual over-read, male or female subjects).
4. 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.
5. Chronic Hepatitis B and C, as evidenced by positive Hepatitis B surface antigen
(HbsAg) or Hepatitis C antibody
6. History of chronic alcoholic liver disease
7. Impaired renal function (estimated GFR<30mL/min)
8. Use of potent CYP3A4 inhibitors (e.g. amiodarone, cyclosporine, diltiazem, elfinavir, indinavir, ritonavir, cimetidine, clarithromycin, erythromycin, fluconazole,
itraconazole, ketoconazole, miconazole, nefazodone, verapamil)
9. Use of methotrexate.
10. Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents
(excluding low-dose aspirin) or a condition associated with decreased haemostasis
11. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
12. A history of clinically significant drug or alcohol abuse, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
13. Participation in another investigational drug or device study during the 3 months prior to the Baseline/Randomisation Visit
14. Inability or unwillingness to comply with study restrictions

Exclusion criteria related to OA:
1. Secondary causes of arthritis of the knee including septic arthritis, inflammatory
joint disease, articular fracture, major dysplasias or congenital abnormality,
ochronosis, acromegaly, hemochromatosis, Wilson’s disease, and primary
osteochondromatosis
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 musculoskeletal or arthritic condition that may affect the interpretation of clinical efficacy and/or safety data or otherwise contraindicates participation in this
clinical study (i.e., currently symptomatic fractures or any concurrent rheumatic
disease such as but not limited to fibromyalgia, rheumatoid arthritis, and Reiter’s
syndrome are excluded)
7. Use of any analgesic, COX-2 inhibitor or NSAID [including topical NSAIDs;
excluding low-dose aspirin (=325mg per day)], other than protoc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To investigate the effects of the CB2 agonist GW842166X on Pain Intensity and sensory endpoints in patients with painful osteoarthritis (OA) of one index knee<br>• To assess the value of experimental endpoints (capsaicin-evoked hyperalgesia, quantitative sensory testing, contact heat-evoked potentials and quantitative sensory tests) as markers of sensitisation in OA arthralgia and/or pharmacodynamic (PD) markers for CB2 agonists<br>;Secondary Objective: • To evaluate the safety and tolerability of GW842166X in patients with OA;Primary end point(s): • Change in Pain Intensity from baseline to the end of treatment using Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain subscore.