A Study of the Efficacy and Safety of 2PX in Patients With Pain Due to Osteoarthritis of the Knee

The purpose of the study is to demonstrate the superiority of topically administered 2PX versus placebo (vehicle) control in terms of reduction in pain intensity and physical function.

Primary objective: To demonstrate the superiority of topically administered 2PX versus placebo (vehicle) control in terms of reduction in pain intensity and physical function.

Secondary objectives: To prospectively measure other efficacy variables of topically administered 2PX in pain associated with osteoarthritis of the knee. To evaluate the safety and tolerability of topically administered 2PX.

Eligibility Criteria:
Inclusion Criteria:

* Male and female out-patients, 40 years or older.
* Subjects with documented OA of either one or both knees, as defined by the American College of Rheumatology (ACR) criteria (\[Altman R, Asch E, Bloch D, et al (1986)\]); i.e.knee pain and at least 3 out of the following 6 criteria in the target joint:

  * age \>50 years
  * stiffness \< 30 minutes
  * crepitus
  * bony tenderness
  * bony enlargement
  * no palpable warmth
* Radiological evidence of joint space narrowing in the target joint within 8 weeks prior to randomisation.
* Subjects with chronic, moderate to severe OA pain of the target knee:

  * present for more than 3 months, and for ≥ 20 days per month.
  * not controlled by, or intolerant of, oral NSAIDs, paracetamol, COX-2 inhibitors or weak opioids.
  * intensity at least moderate (i.e., actual WOMAC (pain questions 1-5) ≥ 10) on WOMAC OA index LK 3.1 at Visit 1, in the target knee, as recalled over the last 24 hours.

Exclusion Criteria:

* Subjects with any moderate to severe pain of other origin (e.g., fibromyalgia) which could confound assessment or self-evaluation of pain due to OA in the target knee.
* Subjects with any prosthesis fitted to the target knee.
* Subjects requiring treatment with any of the following agents/therapies within the specified periods or at any time during the study are excluded from participation:
* Any potent/strong opioid in the 4 weeks prior to randomisation (i.e., an opioid assumed to cause withdrawal symptoms upon abrupt discontinuation).
* Any topical or subcutaneously applied analgesic agents (e.g., capsaicin, NSAIDs) applied to the target knee within 7 days prior to randomisation.
* Any treatment which could alter the degree or nature of baseline OA pain planned within the study period.
* Intra-articular injections of corticosteroids in the target knee within the 2 months prior to randomisation.
* Intra-articular injections of hyaluronan in the target knee within 6 months prior to randomisation.
* Avascular necrosis in the target knee within 6 months prior to randomisation.
* Arthrosynthesis of the target knee within 12 months prior to randomisation.
* Arthroscopy of the target knee within 6 months prior to randomisation.
* Major trauma to the target knee within 6 months prior to randomisation.
* Infection in the target knee within 6 months prior to randomisation.
* Subjects who have previously been treated with 2PX.
* Subjects who have received an investigational drug or used an investigational device within the 30 days prior to randomisation.
* Subjects with a significant psychiatric disorder, in the opinion of the investigator, or subjects receiving strong anti-psychotic medication.
* Subjects with documented or suspected alcohol or drug abuse.
* Any ongoing or past history of malignant disease within the 5 years immediately prior to randomisation (with the exception of basal cell carcinoma).
* Pregnancy or ongoing lactation
* Female subjects of childbearing potential unwilling to use adequate contraceptive measures throughout the duration of the study. For the purpose of this study, adequate contraception is defined as:

  * oral, injected or implanted hormonal methods of contraception; OR
  * placement of an intrauterine device (IUD) or intrauterine system (IUS); OR
  * barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository Note: Male sterilisation or abstinence are not acceptable methods of birth control and would preclude enrolment in the study.

Note: For post-menopausal women: less than 12 months since the last spontaneous menstrual bleeding will exclude the patient unless they are willing to utilise acceptable methods of contraception for the duration of the study.

* Male subjects able to conceive, who are unwilling to use barrier methods of contraception throughout the duration of the study
* Subjects unable to comply with the study assessments.