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

• WOMAC Osteoarthritis Index LK 3.1; total and non-pain subscales: [ Time Frame: At Screening, Baseline, Weeks 2, 4, 12, 26 and 27. ] [ Designated as safety issue: No ]
• Pain intensity will be assessed by asking the question 'What is the level of pain in your target knee right now? [ Time Frame: Daily ] [ Designated as safety issue: No ]
• Patient Global Impression of Change (PGIC) [ Time Frame: At weeks 12 and 26 ] [ Designated as safety issue: No ]
• Clinician Global Impression of Change (CGIC) [ Time Frame: At weeks 12 and 26 ] [ Designated as safety issue: No ]
• Use of rescue medication: The number of paracetamol tablets used each day will be recorded. [ Time Frame: Daily ] [ Designated as safety issue: No ]
• Incidence of Disease Flares: The number and extent of flares in osteoarthritis pain of the target knee between active and placebo groups during the course of treatment. [ Time Frame: At weeks 2, 4, 12, 26, and 27 ] [ Designated as safety issue: No ]

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.

• Pain
• Osteoarthritis

• Drug: strontium chloride hexahydrate
  Topical solution to be applied twice daily for 26 weeks. Dosage of up till 4 ml per application.
• Drug: Placebo
  Topical solution to be applied twice daily for 26 weeks. Dosage up till 4ml per application.

• Experimental: 2PX
  Pain medication
  Intervention: Drug: strontium chloride hexahydrate
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

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.