E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Venous Insufficiency (CVI) CEAP Class C3 or C4 |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066682 |
E.1.2 | Term | Chronic venous insufficiency |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 show the superiority of Doxium® 500 versus placebo in the reduction of oedema of the lower limbs in patients suffering from CVI CEAP Class C3 or C4 |
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E.2.2 | Secondary objectives of the trial |
• Efficacy variables: circumferences of the calf and the ankle, quality of life (questionnaire CIVIQ), symptoms (pain, discomfort, heavy and tired legs, tingling, itching and cramps), efficacy evaluation by both the investigator and the patient
•Safety aspects and tolerability of the trial medication
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patient
• Age 18 to 70 years
• Suffering from unilateral or bilateral CVI CEAP Classes C3 or C4 both at screening (V1) and baseline (V2) visits, assessed by clinical examination (V1 and V2) and duplex sonography (within one month before V1)
• Presence of pitting oedema and at least one of the following two clinical symptoms, discomfort or pain, in at least one leg at both screening and baseline visits
• Chronic oedema at a stable stage
• Written informed consent
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E.4 | Principal exclusion criteria |
• Diseases/symptoms that imitate the symptomatology of CVI (i. e. cardiac, hepatic, renal, orthopaedic, or other causes of leg oedema)
• Manifest cardiac insufficiency (Stage NYHA III or IV)
• Diabetes mellitus (Type I or II)
• Hypertension requiring a change in antihypertensive treatment within 6 weeks before study starts
• Operations of the venous system, sclerotherapy during the last 6 months
• Compression therapy within the last 6 weeks
• Phlebitis or deep leg vein thrombosis in the 3 months preceding inclusion in the study
• Any chronic disease which may impair the patient’s ability to participate in the study (i. e. severe congestive heart failure, active gastric or duodenal ulcer, etc.)
• Asymptomatic and/or symptomatic peripheral occlusive arterial disease (Ankle/Brachial Index < 0.8)
• Primary or secondary lymphoedema
• Clinical manifest lipoedema
• Important obesity (BMI > 40 kg/m2)
• Diseases of the gastrointestinal tract, which would impair absorption of the study medication
• Competing/interfering systemic or local drug treatments (no new medication with a vascular or cardiovascular effect may be taken /administered during the treatment period)
• Participation in another clinical trial and/or treatment with an experimental drug within one month before study start
• Patients with a known allergy or previous intolerance and/or known hypersensitivity to the study medication
• Markedly irregular menstrual cycle (less than 24 or more than 34 days)
• Female patients who are pregnant, lactating or of childbearing potential and not protected from pregnancy by a sufficiently reliable method (OCs, IUD) (Pearl-Index < 1)
• Initiation, change or discontinuation of hormone therapy within the past 3 months
• Active malignant disease within the last 3 years
• Unreliable patients including non-compliant patients, patients with known alcoholism or drug abuse or with a history of a serious psychiatric disorder as well as patients unwilling to give informed consent or to abide by the requirements of the protocol
Additionally, the patient shall not meet any of the following exclusion criteria at V2:
• Severe renal insufficiency, i. e. serum creatinine >150 µmol/L
• Severe hepatic insufficiency, elevated transaminases, i. e. ALAT and ASAT > twice the upper limit of normal
• Significant neutropenia, i. e. WBC < 3.5 G/L
• Acute inflammation, e. g. leukocytes > 10 G/L
• Hypoalbuminaemia < 35 g/L
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the relative volume change in the most pathological leg using water displacement volumetry. |
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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 | 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) | 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) | 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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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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Last subject last visit in this clinical 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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |