A Study Of The Effects Of CB2 Compound Of GW842166 In Patients With Osteoarthritis

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00479427
First received: May 24, 2007
Last updated: July 22, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Osteoarthritis
Drug: GW842166
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo Controlled Cross-over Study of the Effects of the CB2 Compound of GW842166 in Patients With Osteoarthritis

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change in Pain Scores from baseline to the end of treatment using WOMAC on the pain subscore for 6-8 weeks. [ Time Frame: for 6-8 weeks ]

Secondary Outcome Measures:
  • -Change in pain score from baseline to the end of treatment by using Physician's and Patients Global assessments of arthritis condition for 6-8 weeks. [ Time Frame: for 6-8 weeks ]
  • -To use Quantitative Sensory Testing rating heat pain threshold and tolerance for 6-8 weeks. [ Time Frame: for 6-8 weeks ]
  • Change in Pain Intensity from baseline to the end of treatment in WOMAC pain subscore of question 1 (pain walking on a flat surface, Appendix 2)
  • Change from baseline to the end of treatment in WOMAC stiffness subscore (Appendix 2)
  • Change from baseline to the end of treatment in WOMAC physical function subscore
  • Change from baseline to the end of treatment in WOMAC composite score
  • Change from baseline to the end of treatment in Patient's Global assessment of arthritis condition (section 6.6.3)
  • Change from baseline to the end of treatment in Physician's Global assessment of arthritis condition (section 6.6.4)
  • Time and pain intensity (100mm Visual Analogue Scale, VAS) from the 40m self-paced walk test (section 6.6.5, optional)
  • Time and pain intensity (100mm VAS) from the 11 step stair climb test (section 6.6.6, optional)
  • Percentage of patients discontinuing due to lack of efficacy
  • Average total daily use of rescue medication

Estimated Enrollment: 45
Study Start Date: July 2007
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GW842166
    Other Name: GW842166
  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00479427

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, W12 0NN
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, PhD GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00479427     History of Changes
Other Study ID Numbers: CBA106191
Study First Received: May 24, 2007
Last Updated: July 22, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
osteoarthritis pain assessments

Additional relevant MeSH terms:
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on August 28, 2014