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

NCT00479427 | Completed Phase 2

• 1 other identifier: CBA106191
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis

Keywords

osteoarthritis pain assessments

Outcome Measures

Primary Outcomes (1)

• 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

  The index consisted of 24 questions (5 for pain, 2 for stiffness and 17 for physical and composite functions). The visual analog scale (VAS; 0-100 millimeter \[mm\]) was utilized in this study and participants were asked to rate joint pain they had in last 24 hours in the 5 pain items. Participants were asked to rate pain while performing following activities: walking on a flat surface, going up or down stairs; at night while in bed; sitting or lying and standing upright. Higher score (100) indicates extreme pain and lower score (0) indicates no pain. It was assessed on Day 1 pre-dose (Baseline), Day 1 (1 hour post-dose) and Day 14 (2-4 hours post-dose). Change from Baseline was planned to be calculated by subtracting Baseline value from post-Baseline value. Due to the early termination of this study, no formal statistical analysis was performed. Only summarized data is available.

  Baseline (Day 1 pre-dose) and up to Day 14 of each treatment period (approximately up to 8 weeks)

Secondary Outcomes (8)

• Quantitative Sensory Testing (QST) rating heat pain threshold and tolerance for 6-8 weeks

  Up to Day 14 of each treatment period (approximately up to 8 weeks)

• Change from Baseline to the end of treatment in WOMAC stiffness subscore

  Up to Day 14 of each treatment period (approximately up to 8 weeks)

• Change from baseline to the end of treatment in WOMAC physical function subscore

  Baseline (Day 1 pre-dose) and up to Day 14 of each treatment period (approximately up to 8 weeks)

• Change from baseline to the end of treatment in participants' and Physician's Global assessment of arthritis condition

  Baseline (Day 1 pre-dose) and up to Day 14 of each treatment period (approximately up to 8 weeks)

• Time for the 40 meter self-paced walk test and 11 step stair climb test

  Up to Day 14 of each treatment period (approximately up to 8 weeks)

Study Arms (1)

Overall study

EXPERIMENTAL

overall study population

Drug: GW842166; Drug: Placebo

Interventions

GW842166 DRUG

100 mg once daily

Overall study

Placebo DRUG

once daily

Overall study

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, W12 0NN, United Kingdom

Location

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2007
• First Posted: May 28, 2007
• Study Start: July 6, 2007
• Primary Completion: October 9, 2007
• Study Completion: October 9, 2007
• Last Updated: July 11, 2017

Record last verified: 2017-07

Locations

GB (1)