| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Dyslipidemia with uncontrolled elevated triglycerides |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058110 |
| E.1.2 | Term | Dyslipidemia |
|
| 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 assess efficacy of V0002 CA 1 g at 3 capsules /day on preventing niacin-induced flushing promoted by Niaspan® administration |
|
| E.2.2 | Secondary objectives of the trial |
_ To assess efficacy of the treatment combination on LDL-C, HDL-C, Triglycerides during 4 weeks in comparison to placebo
_ To assess efficacy of the combination on other lipoproteins, apolipoproteins, and biological markers during 4 weeks in comparison to placebo
_ To evaluate clinical and biological tolerability |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
_ Male or female outpatients, aged 18 to 75 years inclusive
_ Having given their written informed consent
_ With a Body Mass Index (BMI) < 30 kg/m2
_ Presenting primary or secondary prevention for cardiovascular disease
_ With a known dyslipidemia with uncontrolled elevated triglycerides, confirmed in patient history
_ Counseled to follow the Therapeutic Lifestyle Change (TLC) according to NCEP-ATP-III guidelines (or local equivalent)
_ Treated by one single statin at fixed doses for at least 3 months prior to inclusion
_ With an indication for Niaspan® treatment as shown by a biochemistry and lipid profile performed within 3 months of inclusion, specifically showing HDL-C ≤ 40 mg/dl for men, HDL-C ≤ 50 mg/dl for women |
|
| E.4 | Principal exclusion criteria |
Criteria relative to the target disease :
_ Triglycerides above 10g/l
_ Menopausal women presenting flushes
Criteria relative to treatments :
_ History of allergy or hypersensitivity reaction to the study medication and their excipients
_ History of serious allergy or hypersensibility reaction to any medication
_ Known contraindication to the use of HMG CoA reductase inhibitor (statin)
_ Treatment by a lipid lowering agent other than an HMG CoA reductase inhibitor (statin)
_ Any other treatment likely to interfere with lipid metabolism
_ Patients treated by an anticoagulant drug
_ Patients treated by aspirin and likely to change their dose (continuous low dose of aspirin (< ou = 100mg/day) is permitted during the study for prevention of cardiovascular risk)
General criteria :
_ Childbearing potential women not using an appropriate contraceptive method, (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide, abstinence)
_ Pregnant or breastfeeding women (supported by a negative pregnancy urine test)
_ Uncontrolled arterial hypertension (SBP > 145 mmHg or DBP > 95 mmHg) under blood pressure treatment
_ Uncontrolled hypothyroidism defined as TSH > 2 x the upper limit of normal (ULN) - Thyroid dysfunction controlled for at least 6 months prior to screening is permitted
_ Abnormal liver function (hepatocellular insufficiency, chronic or active liver disease, biliary tract disease, sustained elevation of serum liver enzyme ALAT > 2X ULN)
_ CPK >3x ULN
_ Abnormal renal function (clearance of creatinin < 60ml/mn and creatinemia >15mg/l or any renal disease likely to lead to renal dysfunctions)
_ HbA1C > 9 %
_ Type 1 diabetes mellitus, severe cardiac events within the previous 3 months, secondary causes of hyperlipidemia
_ Patients with known hemorrhagic risk (planned surgical intervention, raised erythrocyte sedimentation rate, thrombocytopenia)
_ Arterial bleeding
_ History of unstable angina or acute myocardial infarction
_ Active peptic ulcer disease
_ Personal or familial history of muscular troubles / myalgia
_ History of muscular toxicity provoked by lipid lowering agent (Fibrate and/or statin)
_ History of presence of any organic disorder likely to modify absorption, distribution or elimination of the medication
_ Known alcohol and/or any other drug abuse or dependence. Alcohol consumption of more than 3 alcoholic beverages per day is considered abusive. One alcoholic beverage is defined as 30 mL distilled spirits, 120 mL wine, or 330 mL beer
_ Patients likely to be non-compliant
_ Patients who have already been included in this study or who are participating in another clinical trial with medicines
_ Patients having received any other investigational agent within 3 months before randomization
_ Patient with any significant history of non-compliance to medical regimens or likely to be non-compliant or with inability to grant reliable informed consent
_ Patient not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force
_ Patients who have donated blood or blood products within the previous month prior to screening or who plan to donate blood or blood products at any time during the trial and in the 3 months following the end of the study
_ Patients who have received more than 4500 euros as indemnities for his participation to other clinical trials, including the present trial, within the last 12 months |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy criteria :
Primary :
_ Global intensity of flush, (flush being defined as the presence of at least one of the 4 following symptoms: redness, warmth, tingling, itching) at the first day of each dose increase of Niaspan®, following D1, D8, D15, D22
Secondary :
Lipids :
_ Total Cholesterol, LDL-C, HDL-C, non-HDL-C, Triglycerides
_ Apolipoproteines: Apo A1, Apo A2, Apo B, Apo C3, Lp(a), fibrinogen, homocystein, CRP
Niaspan®-induced flushes :
_ Mean global intensity of flush, including redness, warmth, tingling or itching at each weekly period of escalating Niaspan® dose
_ Mean global intensity of flush, including redness, warmth, tingling or itching over the 28 day treatment period
_ Presence or not of daily flushing symptoms, including redness, warmth, tingling or itching
_ Number of daily flushing symptoms, including redness, warmth, tingling or itching
_ Duration of the longest daily flushing symptoms, including redness, warmth, tingling or itching
_ Intensity of daily flushing-related to redness
_ Intensity of daily flushing-related to warmth
_ Intensity of daily flushing-related to tingling
_ Intensity of daily flushing-related to itching
_ Global Flush Score “GFS” calculated as daily number of flushes multiplied with the daily global intensity of flush
_ Number of patients withdrawn from study due to flushes will be compared between treatment groups at the end of the study and on the period of each dose of Niaspan®
Safety criteria :
_ Adverse events, clinical examination, vital signs
_ Hematology: hemoglobin (Hb), red blood cell (RBC) count, hematocrit (Ht), total and differential white blood cell (WBC) count, platelet count
_ Biochemistry : transaminases (ASAT, ALAT), alkaline phosphatase (ALP), GGT, CPK, serum creatinine, creatinine clearance, fasting glycaemia, bilirubin (total and conjugated), electrolytes (potassium, calcium, phosphorus), uric acid, LDH, amylase. |
|
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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) | 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 | 48 |
| 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
| |
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
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