| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hypercholesterolemia or Low HDL-C |
|
| E.1.1.1 | Medical condition in easily understood language |
| High bad cholesterol or low good cholesterol |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| 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 |
1. To evaluate the efficacy of anacetrapib 100 mg for 24 weeks relative to placebo on plasma concentrations of LDL-C (BQ method).
2. To evaluate the efficacy of anacetrapib 100 mg for 24 weeks relative to placebo on plasma concentrations of HDL-C.
3. To evaluate the safety and tolerability of anacetrapib 100 mg for 24 weeks. |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of adding anacetrapib 100mg for 24 weeks relative to placebo on plasma concentrations of non-HDL-C.
2. To evaluate the efficacy of adding anacetrapib 100mg for 24 weeks relative to placebo on plasma concentrations of apoB.
3. To evaluate the efficacy of adding anacetrapib 100mg for 24 weeks relative to placebo on plasma concentrations of apoA-1.
4. To evaluate the efficacy of adding anacetrapib 100mg for 24 weeks relative to placebo on plasma concentrations of Lp(a).
5. To evaluate the effect of anacetrapib 100 mg on HDL-C in patients with low HDL-C at LDL-C goal after 24 weeks of treatment.
6. To evaluate the LDL-C-decreasing efficacy of anacetrapib 25 mg vs. placebo after 24 weeks of treatment.
7. To evaluate the HDL-C-increasing efficacy of anacetrapib 25 mg vs. placebo after 24 weeks of treatment.
8. To evaluate the efficacy of adding anacetrapib 25mg for 24 weeks relative to placebo on plasma concentrations of non-HDL-C...
...See protocol. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients will be eligible to continue to Visit 2 if they meet the following criteria at Visit 1:
1. Patient is male or female and ≥18 and ≤80 (or maximum age less than 80; per local regulation) years of age on day of signing informed consent.
2. A female patient should NOT be of reproductive potential. A female patient not of reproductive potential is defined as: one who has either 1) reached natural menopause defined as age 46 or older with a) 12 months of spontaneous amenorrhea or b) 6 months of spontaneous amenorrhea with serum FSH levels in the postmenopausal range as determined by the central laboratory, 2) 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation.
3. As per NCEP ATP III CHD risk category at screening, patients are required to meet ONE of the following criteria:
a. Very high risk patients (presence of established CHD or other forms of atherosclerotic vascular disease plus multiple major risk factors [e.g. diabetes], severe and poorly controlled risk factors [e.g. cigarette smoking], multiple risk factors of the metabolic syndrome [e.g. high triglycerides ≥200mg/dL (2.26 mmol/L) plus non-HDL-C ≥130 mg/dL (3.36 mmol/L) with low HDL-C <40mg/dL (1.03 mmol/L)] or acute coronary syndrome.) with LDL-C ≥70 to <115 mg/dL (≥1.81 to <2.97 mmol/L)
b. High risk patients (CHD or CHD risk equivalent, DM, 10-yr risk>20%) with LDL-C ≥100 to <145 mg/dL (≥2.59 to <3.75 mmol/L)
c. Moderate risk patients(≥2 risk factors; 10-yr risk ≤20%) with LDL-C ≥ 130 mg/dL (≥ 3.36 mmol/L)
d. Lower risk patients (0 to 1 risk factor) with LDL-C ≥ 160 mg/dL (≥4.14 mmol/L)
e. Patients at LDL-C goal (as per CHD- risk category) and with low HDL-C, <40 mg/dL (1.03 mmol/L)
4. Patient has been treated with an appropriate dose of statin as assessed by the investigator (i.e. one of the following) for at least 6 weeks prior to Visit 1:
simvastatin 40 mg or 80 mg
atorvastatin 20 mg, 40 mg or 80 mg
rosuvastatin 5 mg, 10 mg, 20 mg or 40 mg
pitavastatin 4 mg
lovastatin 80 mg
pravastatin 80 mg
Note: Lipid modifying therapy must be stable for at least 6 weeks prior to Visit 1. Patients are expected to take statin under supervision of their treating physician in accordance with statin product circular in that region.
5. Patients provide written informed consent/assent for the trial. The patient may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
Note: Patient with laboratory values outside ranges described in the protocol may, at the discretion of the investigator, have ONLY ONE repeat determination performed and if the repeat value satisfies the criterion patient may continue.
Patients are eligible for randomization if they meet the following criteria at Visit 3:
6. Patient is greater than 75% compliant with study medication during the single-blind placebo run-in phase or in the opinion of the investigator, compliance will improve
following additional counseling. |
|
| E.4 | Principal exclusion criteria |
Visit 1
1. Patient has previously participated in a study with a CETP inhibitor.
2. Patient has homozygous familial hypercholesterolemia.
3. Patient has a TG > 600 mg/dL (6.78 mmol/L)
4. Patient has creatine phosphokinase (CPK) >2 x upper limit of normal (ULN) [per central laboratory reference ranges].
5. Patient has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN) [per central laboratory reference ranges].
6. Patient has severe chronic heart failure defined by New York Heart Association (NYHA) Classes III or IV.
7. Patient has uncontrolled cardiac arrhythmias, MI, PCI, CABG, unstable angina, or stroke within three months prior to Visit 1.
8. Patient has uncontrolled hypertension defined as follows:
- Sitting diastolic blood pressure ≥100 mmHg, or sitting systolic blood pressure ≥160 mm Hg (non-diabetic patients).
OR
- Sitting diastolic blood pressure ≥90 mmHg, or sitting systolic blood pressure ≥150 mm Hg (diabetic patients).
9. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia).
Note: Patients with thyroid stimulating hormone (TSH) values outside the central laboratory normal range who are determined to be without symptoms of either hypo- or hyperthyroidism may be allowed in the study if, after review by the Investigator and Project Physician, the patient is deemed not to have clinically significant thyroid hormone excess or deficiency.
10. Patient has active or chronic hepatobiliary, hepatic or gall bladder disease. Note: Patients with chronic hepatitis B or C or non-alcoholic steatosis are allowed in the study if ALT and AST are within protocol-specified range
11. Patient has eGFR <30 mL/min/1.73m2 based on the 4-variable MDRD (Modification of Diet in Renal Disease) equation, nephrotic syndrome or other clinically significant renal disease.
12. Patient has history of mental instability, drug/alcohol abuse within the past five years or major psychiatric illness inadequately controlled and unstable.
13. Patient has history of ileal bypass, gastric bypass, or other significant condition associated with malabsorption.
14. Patient is human immunodeficiency virus (HIV) positive (as assessed by medical history).
15. Patient has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
16. Patient has donated blood products or has had phlebotomy of >300 mL within eight weeks of signing informed consent, or intends to donate 250 mL of blood
products or receive blood products within the projected duration of the study.
17. Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or
interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
18. Patient is currently taking medications that are potent inhibitors or inducers of CYP3A4 (including but not limited to cyclosporine, systemic itraconazole or ketoconazole, erythromycin, clarithromycin, or telithromycin, nefazodone, protease inhibitors, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St John’s wort) or has discontinued treatment <3 weeks prior to Visit 1. Consumption of >1 liter of grapefruit juice per/day is also prohibited.
19. Patient is currently participating or has participated in a study with an investigational compound or device within three months of signing informed consent.
20. Patient consumes more than two alcoholic drinks per day.
21. Patient is receiving treatment with systemic corticosteroids.
Note: Treatment with corticosteroids used as replacement therapy for pituitary/adrenal disease is acceptable; however, the patient must have been on a stable regimen for at least six weeks prior to Visit 1.
22. Patient is taking systemic anabolic agents. Additional details regarding excluded concomitant medications can be found in Appendix 6.10 of the protocol.
Note: Patient with laboratory values outside ranges described in the protocol may, at the discretion of the investigator, have ONLY ONE repeat determination
performed and if the repeat value satisfies the criterion patient may continue.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- LDL-C (BQ method)
- HDL-C |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
- LDL-C (BQ method): at visits 3, 4, 5, 6 and 7
- HDL-C: at visits 3, 4, 5, 6 and 7 |
|
| E.5.2 | Secondary end point(s) |
- non-HDL-C
- apoB
- apoA-I
- Lp(a)
- HDL-C in patients with low HDL-C at LDL-C goal |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- non-HDL-C: at visits 3, 4, 5, 6 and 7
- apoB: at visits 3, 4, 5, 6 and 7
- apoA-I: at visits 3, 4, 5, 6 and 7
- Lp(a): at visits 3, 6 and 7
- HDL-C in patients with low HDL-C at LDL-C goal
Please see study flow chart for clearer information. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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) | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| 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 | No |
| 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 |
| Bulgaria |
| France |
| Germany |
| Hungary |
| Israel |
| Netherlands |
| Peru |
| Poland |
| Puerto Rico |
| Romania |
| Slovakia |
| Spain |
| United Kingdom |
| United States |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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