| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with hypercholestrolemia or combined dyslipidemia |
|
| 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 |
|
| 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 (up to 1 year) safety and tolerability of pitavastatin 4 mg once daily (QD). |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the long-term efficacy of pitavastatin 4 mg QD on LDL-C levels and on other lipid and lipoprotein fractions (TC, HDL-C, TC:HDL-C ratio, TG, apolipoprotein A1 and B [Apo-A1, Apo-B]), hs-CRP, oxidized LDL and LDL-C target attainment (European Atherosclerosis Society [EAS] and National Cholesterol Education Program [NCEP]). |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1). Patients have completed 12 weeks of treatment in Study NK-104-301 or NK-104-302;
2). Males and females (age 18-75 years at the start of the core study). Non-pregnant, non-lactating females;
3). Patients who have not developed any treatment emergent and in the opinion of the investigator related, AE of clinical significance where the investigator is uncomfortable with continuing the patient on therapy with pitavastatin.
4). Women of child bearing potential are allowed to enter the study ONLY if they use sustained contraceptive preparations (e.g., implants or intramuscular [IM] injections) or comply with an approved mechanical contraceptive method. A woman is considered to be of childbearing potential unless she is post-hysterectomy or at least 1-year post-menopausal or post-tubal ligation. All women of child bearing potential must have a negative pregnancy test at the end of the core study (NK-104-301 or NK-104-301);
5). 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;
6). Patients who have been following a fat and cholesterol restrictive diet as advised by the EAS during the dietary stabilization lead-in period before the start of the core study and through-out the entire core study (NK-104-301 or NK-104-302); and
7). Patients who agree to be available for every clinic visit, which will occur in the morning. |
|
| 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 12 months from 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 symptoms for at least the last 6 months prior to the study start will be allowed to enter the 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] >3 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 without clinical explanation in the absence of conditions explaining the CK elevation the patient will be immediately excluded from further study participation;
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). 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;
12). Symptomatic cerebrovascular disease including cerebrovascular hemorrhage, transient ischemic attack, or carotid endarterectomy;
13). 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;
14). 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;
15). Drug abuse or continuous consumption of more than 65 mL pure alcohol per day (e.g., more than 4 x 125-mL glasses of wine or 3 glasses of spirits per day);
16). Current or recent (within 1 week of Visit 1 [Week 0]) use of supplements or medications known to alter lipid metabolism e.g. soluble fibers (including >2 teaspoons Metamucil or psyllium containing supplement per day), or other dietary fiber supplements, fish oils containing Omega 3 oils, or other products at the discretion of the investigator. ... However, their use must be stopped at least 1 week prior to Visit 1 of the extension study (NK 104 307);
17). Any concomitant medication not permitted by this protocol;
18). Excessive obesity defined as Body Mass Index (BMI) above 35 kg/m2 (BMI = body weight in kg divided by squared height [m2]). Body Mass Index values should be rounded to the nearest whole number: down at <0.5 and up at ≥0.5; |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Long term safety and tolerability of Pitavastatin 4 mg QD is assessed for a period of up to 1 year. |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | 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 |
|
| 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
| |
| 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 | |
| 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 |
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