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 | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031161 |
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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 that lumiracoxib 100 mg o.d. has an improved 24-hour BP profile compared to ibuprofen 600 mg t.i.d. with respect to the effect on Ambulatory Blood Pressure Monitoring (ABPM) after 4 weeks of treatment (defined as change from baseline in average 24-hour systolic BP) in OA patients with controlled hypertension.
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E.2.2 | Secondary objectives of the trial |
Assess the effect of lumiracoxib 100 mg o.d. on diastolic BP derived from ABPM after 4 weeks of treatment in comparison to ibuprofen 600 mg t.i.d. (defined as change from baseline in average 24-hour diastolic BP).
Assess the effect of lumiracoxib 100 mg o.d. on daytime and nighttime BP (systolic and diastolic) derived from ABPM after 4 weeks of treatment in comparison to ibuprofen 600 mg t.i.d.
Assess the effect of lumiracoxib 100 mg o.d. on the incidence of significant increases in ABPM (defined as an increase in 10 mmHg in systolic and/ or 5 mmHg in diastolic BP) in comparison to ibuprofen 600 mg t.i.d.
Perform an exploratory analysis of the effect of lumiracoxib 100 mg o.d. on the incidence of uncontrolled hypertension (defined as an increase in ABPM from <130/80 mmHg at baseline to ≥130 and/ or ≥80 mmHg after 4 weeks of treatment) in comparison to ibuprofen 600 mg t.i.d. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Signed written informed consent before any study procedure is performed.
2. Cooperative male or female outpatients of at least 50 years of age.
3. Female patients must be either post-menopausal for one year, surgically sterile, or using effective contraceptive methods such as barrier method with spermicide or intra-uterine device. Oral contraceptives use is not allowed 4 weeks prior screening and throughout the duration of the study. Patients on hormonal replacement therapy are allowed if they have been on a stable dose for at least 6 months.
4. Primary OA of the hand, hip or knee according to ACR criteria or OA of the spine. One joint will be identified as the target joint and will be evaluated throughout the duration of the trial.
5. Is expected to need NSAID or simple analgesic therapy for OA for at least the next 6 weeks.
6. Controlled hypertension with MSSBP <140 mmHg and MSDBP <90 mmHg (mean of 3 cuff BP measurements). Patients must have taken the same fixed dose of antihypertensive medication(s) on a regular basis for at least 3 consecutive months prior to screening and are not expected to adjust their antihypertensive medication(s) during the study.
7. Regular wake-up times which are expected to continue for the duration of the trial.
8. Agreement on being available for every study visit which will have to occur in the morning between 0700h and 1100h.
9. Compliance of ≥80% (at least 80% of tablets scheduled per day) during the wash-out phase (to be assessed only before start of first ABPM evaluation/ Visit 2).
10. Mild, moderate or severe pain in the affected joint as assessed on a categorical 5-point Likert scale as per Appendix 5 at baseline/ Visit 3.
11. A successfully completed baseline ABPM evaluation
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E.4 | Principal exclusion criteria |
1. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
2. History of asthma, acute rhinitis, nasal polyps, angioneurotic edema, urticaria or other allergic-type reactions after taking acetylsalicyclic acid or NSAIDs.
3. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml).
5. History of cardiac and cerebral thrombotic/ ischemic diseases and/ or events as listed below: • angina pectoris (of any severity) or other evidence of coronary heart disease; • myocardial infarction; • coronary heart disease with ECG-evidence of silent myocardial infarction; • coronary artery bypass grafting (CABG) or percutaneous coronary intervention (any PCI procedure); • clinically significant carotid artery stenosis or history of carotid endarterectomy; • congestive heart failure, NYHA class II – IV; • second or third degree heart block in the absence of permanent pacing and all potentially life-threatening arrhythmia or symptomatic arrhythmia; • clinically significant valvular heart disease; • cerebrovascular disease; • peripheral arterial disease
6. Evidence of: • Hepatic disorder (ALT or AST >1.5x upper normal limit [ULN]); bilirubin >1.2 x ULN unless secondary to Gilbert’s disease in the opinion of the investigator) • Renal disorder (serum creatinine >1.25 x ULN) • Blood coagulation disorder (i.e. hemophilia) • Anemia (hemoglobin more than 2 g/dL [20 g/L] below the lower limit of normal). • Platelet count < 100 x109/L
7. Evidence of a secondary hypertension, such as coarctation of the aorta, hyperaldosteronism, renal disease, or pheochromocytoma, etc.
8. Rheumatoid arthritis, psoriatic arthritis, adult juvenile chronic arthritis (juvenile chronic arthritis with continued activity in adulthood).
9. Evidence of active peptic ulceration within the previous 12 months.
10. History of gastrointestinal bleeding within the last 5 years (patients with a history of minor lower gastro-intestinal tract bleeding, such as from hemorrhoids or anal fissures are not excluded).
11. Inflammatory bowel disease
12. Moderate to severe renal dysfunction (estimated creatinine clearance <50 mL/min)
13. History of pancreatitis
14. Confirmed Type 1 Diabetes Mellitus.
15. Type 2 Diabetes Mellitus with poor glucose control as defined by persistent fasting blood glucose levels of >200 mg/dL (>11mmol/L), clinically significant diabetic neuropathy or autonomic neuropathy.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is change from baseline at week 4 (defined as the week 4 value minus the baseline value) in average 24-hour ABPM systolic BP. |
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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 | No |
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 | Information not present in EudraCT |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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The study will be considered completed once the last randomized patient has completed his/ her Study Drug Discontinuation visit. |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |