| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033371 |
| E.1.2 | Term | Pain |
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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 |
| The primary objective of this trial is to demonstrate the overall effectiveness (balance of efficacy and tolerability) of a combination of ibuprofen and acetaminophen in community patients with chronic knee pain. |
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| E.2.2 | Secondary objectives of the trial |
To collect and compare Quality of Life (QoL) data from each of the treatment groups and from two different instruments, one generic and one specific.
To determine the prevalence of OA as defined by the American College of Rheumatology (ACR) criteria in patients in the community with chronic knee pain
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Age: Age 40 years or over.
2) Sex: both sexes are eligible for entry. Females of child bearing potential must have a negative urine pregnancy test result at the baseline visit. (Note: this is a home visit, serum pregnancy testing is not practical).
3) Primary diagnosis of chronic knee pain as evidenced by the presence of pain in or around at least one knee for most days over the last three months and pain on at least four of the seven days preceding the screeing visit. Subjects taking analgesic drugs at screening must be willing to discontinue them.
4) Pain of the signal knee, prior to provision of study medication, and, where necessary, after an appropriate washout period on discontinuation of any current analgesic medications, at a level of >30 mm and <80 mm on the VAS (pain experienced in the previous 48 hours) for one or more of the following: walking on a flat surface, going up or down stairs, at night while in bed, sitting or lying, standing upright.
5) Be anticipated to require continuous treatment to control pain for the duration of the study.
6) Have a Functional Capacity Classification of I-III.
7) Status: Patients registered with a General Practitioner.
8) Subjects who have given written informed consent.
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| E.4 | Principal exclusion criteria |
1) Concomitant other major rheumatic disease (including rheumatoid arthritis, gout and sero-negative arthropathies) or other painful conditions which could interfere with the accurate assessment of the signal knee, or acute joint trauma of the signal knee or a lower limb joint prosthesis.
2) An anticipated need for any major surgical procedure or any invasive procedure that would be performed on either knee during the course of the study.
3) An active malignancy of any type (subjects who have a history of basal cell carcinoma that has been successfully treated are eligible). Subjects with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before
study enrolment are also eligible).
4) An active or suspected peptic or duodenal ulceration, a history of gastrointestinal bleeding or severe dyspepsia experienced for most days of the previous month.
5) Inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis), a chronic or acute renal or hepatic disorder, a significant coagulation defect, or any previous history of allergy or known intolerance to any of the drugs or formulation constituents which, in the Investigator’s opinion, might preclude use of an NSAID, including aspirin sensitive asthma or a previous allergic response to a NSAID, including bronchospasm, urticaria, angioedema and rhinitis.
6) Ankle oedema.
7) Concomitant medications and treatments (see Section 13): Receipt of any intra-articular hyaluronate in the previous 6 months, or intra-articular corticosteroids within 3 months to the signal joint or intra-articular corticosteroid to any joint within the previous 1 month, or intra-muscular (i.m.) corticosteroid or per oral (p.o.) steroid within the previous month or fluid evacuation without steroid injection, or any drug intended to modify joint structure or function; Subjects taking warfarin and other anticoagulants will be excluded, however, subjects taking ≤ 325 mg aspirin per day for non-arthritic reasons, if stable for at least 30 days prior to first dose of study medication, are eligible. Subjects taking methotrexate will be excluded. If the patient uses a cane or other assisted devices at time of initial evaluation, then the usage must remain unchanged. If the patient is undergoing physiotherapy at the time of initial evaluation, then the regimen must remain unchanged throughout the study.
8) An anticipated need for treatment with other analgesics (such as opiodis/narcotics) during the course of the study.
9) Abnormal pre-treatment laboratory test values 1.5 times the upper limit of normal (ULN) for either aspartate transaminase (AST; SGOT) or alanine transaminase (ALT; SGPT) or any other laboratory abnormalities considered by the Investigator to be clinically significant. If such a value is found at screening, the patient must be excluded.
10) Abuse of alcohol, as evidenced by averaging more than 21 units per week for men or 14 units for women.
11) Woman of childbearing potential, who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions, (i.e. an oral contraceptive, an approved hormonal implant, an intrauterine device or condoms/diaphragm and spermicide). A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or has not undergone an hysterectomy or surgical sterilisation, e.g. bilateral tubal ligation, bilateral ovariectomy (oophorectomy). Women of childbearing potential practising sexual abstinence, and those with a partner who has had a vasectomy, who are not using (or are not willing to use) any of these methods of contraception nor undergone the surgical procedures, must be excluded from the study.
12) Those previously randomised into the study.
13) Those who have participated in a clinical trial in the previous 30 days.
14) Those unable in the opinion of the Investigator to comply fully with the study requirements.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint for safety is the incidence of moderate and severe adverse events (AEs) regardless of the relationship to the assigned treatment. This will be expressed as incidence on a person days basis. AEs will be recorded throughout the study in patient diaries and in the Case Report Form (CRF) in response to questioning by the Investigator at each patient visit (day 10, end week 7, end week 13). Clinically significant changes as judged by the Investigator in haematology, clinical chemistry, urinalysis values or vital signs (including ECGs) will be recorded as adverse events.
The primary endpoint for short-term efficacy is the pain element of the WOMAC OA index subscale for pain (normalised to 0-100 scale) at day 10.
The primary endpoint for long-term efficacy is the patient global assessment of study medication after 13 weeks treatment. This will be assessed on a 5 point Likert scale (excellent, good, fair, poor, unacceptable) in response to the question “overall, taking into account both how your medicine worked for you and any side effects you think it caused you, how would you rate your medication as a treatment for your painful knee?” Patients without week 13 assessment data will have their latest recorded value carried forward.
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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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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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| Provided in the protocol. |
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
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