A 4-week, multicentre, randomized, double-blind, double-dummy, parallel group ambulatory blood pressure monitoring study to demonstrate that treatment with lumiracoxib 100 mg o.d. results in a 24-hour blood pressure profile superior to ibuprofen 600 mg t.i.d. in OA patients with controlled hypertension

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-003286-17-GB
• Date of registration: 26/10/2005
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 4-week, multicentre, randomized, double-blind, double-dummy, parallel group ambulatory blood pressure monitoring study to demonstrate that treatment with lumiracoxib 100 mg o.d. results in a 24-hour blood pressure profile superior to ibuprofen 600 mg t.i.d. in OA patients with controlled hypertension
• Scientific title: A 4-week, multicentre, randomized, double-blind, double-dummy, parallel group ambulatory blood pressure monitoring study to demonstrate that treatment with lumiracoxib 100 mg o.d. results in a 24-hour blood pressure profile superior to ibuprofen 600 mg t.i.d. in OA patients with controlled hypertension
• Date of first enrolment: 06/01/2006
• Target sample size: 1650
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003286-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Austria, Finland, Germany, Sweden, United Kingdom

Key inclusion & exclusion criteria

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Osteoarthritis
MedDRA version: 8.0 Level: LLT Classification code 10031161

Intervention(s)

Trade Name: Prexige
Product Name: Prexige
Product Code: COX189
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: lumiracoxib
Current Sponsor code: COX189
Concentration unit: Bq/mg becquerel(s)/milligram
Concentration type: equal
Concentration number: 100 mg -
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Ibuprofen 600mg Tablets
Product Name: Ibuprofen
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ibuprofen
Concentration unit: Bq/mg becquerel(s)/milligram
Concentration type: equal
Concentration number: 600 mg-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 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.

Main Objective: 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.

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.

Secondary ID(s)

2005-003286-17-DE

COX189A2428

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/01/2017
• Date Completed: 29/09/2006
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-003286-17/results