E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Primary Hypercholesterolemia or Combined Dyslipidemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
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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 assess long-term (≥ 1 year) safety and tolerability of pitavastatin 2 mg and 4 mg once daily (QD). |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term efficacy of pitavastatin 2 mg and 4 mg QD following titration on LDL-C levels and on other lipid and lipoprotein fractions (TC, HDL-C, TC:HDL-C ratio, TG, Apo B and apolipoprotein A1 [Apo A1]), high sensitivity C-reactive protein (hs CRP), oxidized low-density lipoprotein (LDL) and LDL-C target attainment (European Atherosclerosis Society [EAS]/National Cholesterol Education Program [NCEP]). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Patients who have completed 12 weeks treatment in study NK-104-306; 2) Males and postmenopausal females (aged 65 years and older); 3) Patients who have tolerated study treatment in the core study (NK-104-306); 4) Patients who are eligible and able to participate in the study and who have given written informed consent after the purpose and nature of the investigation has been explained to them; 5) Patients who have been following a fat and cholesterol restrictive diet (as advised by the EAS guidelines) for a total of 18-20 weeks in their previous study and will continue this diet in the open-label study; and 6) Patients who agree to be available for every clinic visit, which will occur in the morning.
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E.4 | Principal exclusion criteria |
1) Any conditions which may cause secondary dyslipidemia, should be reassessed at the beginning of the follow-on study. This includes, but is not restricted to alcoholism, auto-immune disease, nephrotic syndrome, uremia, any viral or non viral hepatitis clinically active within 18 months from core study entry, obstructive hepatic or biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage disease, chronic pancreatitis, porphyria, and uncontrolled hypothyroidism or hyperthyroidism (controlled hypo- or hyperthyroidism, [i.e., condition presenting with normal baseline serum thyroid-stimulating hormone {TSH} and treatment stable during at least the last 2 months prior to study entry] will be permitted); 2) Uncontrolled diabetes mellitus as defined by glycosylated hemoglobin A1c (HbA1c) >8% should be reassessed at the beginning of the follow-on study. Patients with controlled Type II diabetes are allowed, provided the disease has been stable during at least the last 3 months prior to study entry; 3) Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by the evidence of any of the following: history of major gastrointestinal tract surgery e.g. gastrectomy, gastroenterostomy, or small bowel resection, gastritis, current active ulcers, gastrointestinal, or rectal bleeding. Current active or recurrent irritable bowel syndrome (IBS) or history of inflammatory bowel syndrome. Patients with a past history of IBS without exacerbation or clinical manifestation throughout the core study will be allowed to enter the follow-on study; 4) Any history of pancreatic injury or pancreatitis, or impaired pancreatic function/injury as indicated by abnormal lipase or amylase; 5) Liver injury as indicated by serum transaminase levels (ALAT/serum glutamic pyruvic transaminase [SGPT], ASAT/serum glutamic oxaloacetic transaminase [SGOT] >2 x upper limit of the reference range (ULRR)) will be immediately excluded from further study participation; 6) Impaired renal function as indicated by serum creatinine levels > 1.5 x ULRR at Visit 1 (Week 0); 7) Current obstruction of the urinary tract or difficulty in voiding due to mechanical as well as inflammatory conditions, which is likely to require intervention during the course of the study or is regarded as clinically meaningful by the investigator; 8) Serum CK >5 x ULRR. If serum CK is between 1.5 and 5 x ULRR a re-test will be allowed. If the repeat CK is >1.5 and < 5 x ULRR and has increased compared to the previous measurement the patient will be immediately excluded from further study participation. In cases when the repeat CK is > 1.5 and < 5 x ULRR and has decreased compared to the previous measurement the patient may be enrolled in the study after consultation and agreement between the Investigator and the sponsor’s medical representative. 9) Uncontrolled hypothyroidism defined as TSH > ULRR; 10) Any severe acute illness or severe trauma in the last 3 months prior to Visit 1(Week 0); 11) Major surgery, during the 3 months prior to Visit 1; 12) Significant CVD such as myocardial infarction, coronary or peripheral artery angioplasty, bypass graft surgery or severe or unstable angina pectoris; 13) Evidence of symptomatic heart failure (New York Heart Association ([NYHA]) class III or IV), gross cardiac enlargement (cardiothoracic ratio >0.5); significant heart block or cardiac arrhythmia. History of uncontrolled complex ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardias with a ventricular response rate of > 100 beats per minute at rest. Patients whose electrophysiological instability are controlled with a pacemaker or implantable cardiac device are eligible; 14) Left ventricular (LV) ejection fraction <0.25; 15) Symptomatic cerebrovascular disease including cerebrovascular hemorrhage, transient ischemic attack, or carotid endarterectomy; 16) Any treatment emergent event in the core study, that at the discretion of the investigator which place the patient at higher risk derived from his/her participation in the study, which could confound the result of the study, or are likely to prevent the patient from complying with the requirements of the study or completing the study period; 17) Known human immunodeficiency virus (HIV) infection; 18) Poorly controlled or uncontrolled hypertension. Patients must have a systolic blood pressure (SBP) ≤160 mm Hg and diastolic blood pressure (DBP) ≤90 mm Hg with or without antihypertensive therapy; 19) Prior or current known muscular or neuromuscular disease of any type; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Long term safety and tolerability of pitavastatin 2mg and 4 mg once daily (QD), following titration, is assessed for a period of ≥ 1 year. |
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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 | No |
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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Information not present in EudraCT |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |