E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pain associated with osteoarthritis of the knee |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031161 |
E.1.2 | Term | Osteoarthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the superiority of topically administered 2PX versus placebo (vehicle) control in terms of reduction in pain intensity and physical function.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
During the study blood samples will be collected from each patient at Weeks 0 (Baseline), 12 and 26 for possible analysis of strontium concentration. It is not anticipated that all samples will be tested moreover a population pharmacokinetic or subgroup analysis may be performed. Individual patient samples may also be analysed in support of investigation into the occurrence of specific adverse events. All samples which are not selected for testing will be destroyed upon completion of the study. If performed, strontium concentrations will be determined at a central laboratory. |
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E.3 | Principal inclusion criteria |
• Male and female out-patients, 40 years or older. • Subjects who have given their written informed consent. • 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., o 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 o 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: o present for more than 3 months, and for ≥20 days per month. o not controlled by, or intolerant of, oral NSAIDs, paracetamol, COX-2 inhibitors or weak opioids. o 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. |
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E.4 | Principal 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: o oral, injected or implanted hormonal methods of contraception; OR o placement of an intrauterine device (IUD) or intrauterine system (IUS); OR o 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 thoughout the duration of the study • Subjects unable to comply with the study assessments.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints are the difference between the active and placebo group in the change from Baseline to the assessment after 26 weeks of treatment in the actual WOMAC Osteoarthritis Index LK 3.1 subscale score for pain and physical function. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |