Clinical trial NCT00479427: A Study Of The Effects Of CB2 Compound Of GW842166 In Patients With Osteoarthritis
Official title: A Double-blind, Placebo Controlled Cross-over Study of the Effects of the CB2 Compound of GW842166 in Patients With Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis
Keywords: osteoarthritis pain assessments
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-05-28
Enrollment: 1
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a double-blind, two-period, placebo controlled cross-over Phase IIa study. This study is to use CB2 compound of GW842166 in patients with osteoarthritis. The pain assessments and WOMAC questionnaires will be used in the study after the repeated dose to evaluate the efficacy of CB2 compound of GW842166.


Eligibility criteria: Inclusion Criteria:

* Male or female patients, 50 to 80 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 (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.
* 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.
* 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)
* Global functional status I, II or III according to ACR classification (see Appendix 5).
* 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.

Patient has a maximum of 80mm on the 100mm VAS (WOMAC pain subscale) at screening.

Exclusion Criteria:

* Intolerance of paracetamol.
* 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).
* 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).
* 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.
* Chronic Hepatitis B and C, as evidenced by positive Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody
* History of chronic alcoholic liver disease
* Impaired renal function (estimated GFR\<30mL/min)
* Use of potent CYP3A4 inhibitors (e.g. amiodarone, cyclosporine, diltiazem, elfinavir, indinavir, ritonavir, cimetidine, clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole, miconazole, nefazodone, verapamil)
* Use of methotrexate.
* Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents (excluding low-dose aspirin) or a condition associated with decreased haemostasis
* 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.
* A history of clinically significant drug or alcohol abuse, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria \[Hochberg, 1991\]
* Participation in another investigational drug or device study during the 3 months prior to the Baseline/Randomisation Visit
* Inability or unwillingness to comply with study restrictions
* An unwillingness of male subjects to use a condom/spermicide, in addition to having their female partner use another form of contraception, such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if engaging in sexual intercourse with a female partner who could become pregnant. This criterion must be followed from the time of the first dose of study medication until three months after the last dose of study medication.

Exclusion criteria related to OA:

* 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
* Had lower extremity surgery (including arthroscopy) within 6 months prior to screening or scheduled for surgery of any kind during the study period
* Significant prior injury to the index knee within 12 months prior to screen
* Use of lower extremity assistive devices other than a cane or knee brace (use of a 'shoe lift' is permitted)
* Disease of the spine or other lower extremity joints of sufficient degree to affect the index knee
* 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)
* Use of any analgesic, COX-2 inhibitor or NSAID \[including topical NSAIDs; excluding low-dose aspirin (≤325mg per day)\], other than protocol defined rescue therapy (paracetamol), within 5× half-life (in hours) prior to the first dosing day or during the study
* Corticosteroid use prior to baseline as follows:

  * Intra-articular injection of steroids to the index knee within the previous 3 months
  * Intra-articular steroid injections into any site other than the index knee within the
  * Intra-muscular corticosteroid injections within the previous 3 months
  * Oral corticosteroids within the previous 1 month
* Received hyaluronan injections into index knee within the previous six months prior to baseline
* Initiation of or change to an established physiotherapy program within 2 weeks prior to baseline or during the study period. An established physiotherapy program may be continued throughout the study period if unchanged in frequency and intensity Recent start or change in dose regimen (≤3 months prior to baseline) of any OA-specific therapies (i.e., nutraceutical products) including but not limited to chondroitin or keratin sulfate, s-adenosyl methionine (SAMe) and glucosamine preparations

Primary outcomes:
measure: Change in pain scores from Baseline to the end of treatment Western Ontario and McMasters University Osteoarthritis Index (WOMAC) using on the pain subscore for 6-8 weeks
timeFrame: Baseline (Day 1 pre-dose) and up to Day 14 of each treatment period (approximately up to 8 weeks)
Secondary outcomes:
measure: Quantitative Sensory Testing (QST) rating heat pain threshold and tolerance for 6-8 weeks
timeFrame: Up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Change from Baseline to the end of treatment in WOMAC stiffness subscore
timeFrame: Up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Change from baseline to the end of treatment in WOMAC physical function subscore
timeFrame: Baseline (Day 1 pre-dose) and up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Change from baseline to the end of treatment in participants' and Physician's Global assessment of arthritis condition
timeFrame: Baseline (Day 1 pre-dose) and up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Time for the 40 meter self-paced walk test and 11 step stair climb test
timeFrame: Up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Pain intensity (100mm VAS) for the 40 meter self-paced walk test and for 11 step stair climb test
timeFrame: Up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Percentage of participants discontinuing due to lack of efficacy
timeFrame: Up to Day 14 of each treatment period (approximately up to 8 weeks)
measure: Average total daily use of rescue medication
timeFrame: Up to Day 14 of each treatment period (approximately up to 8 weeks)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: