A randomized, double-blind, placebo-controlled, parallel group trial of HMR1766 assessing the efficacy and safety of 3 doses of HMR1766 (25, 100, 200 mg OD) versus placebo with cilostazol, 100 mg BID as a calibrator, administered for 26 weeks in patients with Peripheral Arterial Disease (PAD) Fontaine stage II. - ACCELA
- Conditions
- Peripheral Arterial Disease (PAD) Fontaine stage II (intermittent claudication)MedDRA version: 8.1Level: LLTClassification code 10022562Term: Intermittent claudication
- Registration Number
- EUCTR2006-004275-35-FR
- Lead Sponsor
- sanofi-aventis recherche & développement
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 550
Inclusion criteria at screening period
Diagnosis of intermittent claudication (PAD Fontaine stage II):
1. Patient with stable symptoms of intermittent claudication of the lower extremities, secondary to chronic occlusive arterial disease from atherosclerosis etiology (symptoms present for 6 months or longer and not significantly changed within the past 3 months);
and
2. ICD (Initial claudication distance) of 30 to 250 m at screening constant workload treadmill test.
Confirmation of underlying PAD:
3. Ankle/Brachial Index (ABI) of 0.90 to 0.5 or for patients with an ABI greater than 1.3 (due to non-compressible arteries), a Toe-Brachial Index (TBI) of less than 0.7.
Inclusion criteria at randomization
Confirmation of symptom stability:
4. Mean ICD of 30 to 250 m calculated by averaging the constant workload treadmill test performed at the end of the run-in phase and the previous one performed at screening.
5. The maximum change (measured in log) in the claudication distance should not exceed 0.25 between those two ICD measurements, as per international recommendation.
6. The patient is not allowed to smoke 3 hours before treadmill / ABI tests.
Appropriate background therapy:
7. The patients must have optimal cardiovascular risk prevention and appropriate management of PAD, including clopidogrel 75mg per day, during the study treatment period.
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 at screening / randomization visits
1. Patient not having provided written informed consent.
2. Patient participated in investigational clinical trials in the last 2 months prior screening.
3. Pregnant or breast-feeding woman or woman without documented birth control measures for at least 3 months prior to randomization.
Potentially non-atherosclerotic and/or severe stage disease not amenable to medical therapy:
4. Age below 40 years and/or onset of symptoms of PAD before the age of 40 years.
5. Non-atherosclerotic peripheral arteriopathy (e.g. Buerger’s disease, aneurismal states, popliteal entrapment syndrome).
6. Acute peripheral ischemia e.g. thrombosis in situ, trauma, paradoxical embolism of venous thrombi.
7. Critical limb ischemia (equivalent to Fontaine stages III and IV), manifested by ischemic rest pain or trophic lesions.
Recent (within 3 months prior to screening) pharmacological treatment likely to interfere with study endpoints:
8. Recent initiations or discontinuation of treatment by vasoactive agents (e.g. pentoxifylline, beraprost sodium, papaverine, isoxsuprine, nylidrin, cyclandelate and niacin derivatives). Patients treated by cilostazol within 3 months prior to screening will also be excluded.
9. Concomitant treatment with sildenafil or other drug of the same class, from start of the run-in phase, until the end of the trial.
Recent (within 3 months prior to screening or during the run-in phase) changes in local and/or general conditions likely to interfere with study endpoints:
10. Recent lower-extremity surgical or endovascular arterial reconstructions or sympathectomy, or recent deep venous thrombosis.
11. Recent change in the level of compliance to supervised or unsupervised program of exercise training and smoking status.
12. Recent occurrence of at least one of the following: acute myocardial infarction (MI), unstable angina (UA), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), transient ischemic attack (TIA) or stroke; symptomatic cardiac arrhythmias or significant conduction disturbances.
Presence of medical and/or social conditions that would either interfere with participation in the trial, or lead to inability to complete the trial:
13. Conditions other than claudication, limiting their exercise capacity, likely to jeopardize completion and/or safety of the treadmill testing, according to investigator’s judgment.
14. Planned cardiac or vascular surgery or angioplasty or any major surgery within the next 6 months.
15. Severe concomitant disease such that the patient is not expected to survive 6 months.
16. Receipt of any investigational treatment (drug or device) within the previous 2 months.
17. Inadequate control of hypercholesterolemia and diabetes mellitus.
18. Geographic or social factors making study participation impractical.
Contra-indications to the use of clopidogrel, cilostazol, or conditions likely to affect
pharmacokinetics of cilostazol and/or comedication:
19. Contra-indication to the use of clopidogrel.
20. CHF of any severity.
21. History of drug allergy to cilostazol or HMR1766.
22. Severe hepatic disease (hepatic enzymes>3times ULN).
23. Severe renal failure (serum creatinine greater than 2.5 mg/dL).
24. Requirement for systemic administration of inhibitors of CYP3A4 such as ketoconazole, itraconazole, erythromycin, diltiazem, as well as substrates of CYP2C9 such as warfarin, fluvastatin.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: . To demonstrate the efficacy of 6 months treatment with HMR1766 for improvement in walking distance in patients with intermittent claudication (Fontaine II stage PAD).;Secondary Objective: · To assess the safety and tolerability of HMR1766.<br>· To assess steady state PK in a subset of about 90 patients, in selected sites.<br>· To build a population PK model in all study patients.<br>;Primary end point(s): Efficacy endpoint<br>. Primary:<br>percent change in claudication distance (ICD) measured at the 26-week test, compared with baseline value.<br><br>. Secondary:<br>Percent change in absolute claudication distance (ACD) at the 26-week test, compared with the value at baseline.<br><br>
- Secondary Outcome Measures
Name Time Method