| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
Main objective: Assess the effects of ERN/LRPT relative to ERN on flushing during the post-withdrawal dosing period as measured by number of days/week with GFSS ≥4 during weeks 21 to 32.
|
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives:
• Assess the effects of ERN/LRPT relative to ERN on flushing during the post-withdrawal dosing period as measured by percentage of patients with maximum GFSS ≥4 during weeks 21 to 32.
• Assess the safety and tolerability of ERN/LRPT relative to PBO.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient is male or female and ≥18 to ≤75 years of age on day of signing informed
consent.
2. Patient understands the study’s procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written
informed consent.
3. Patient is a male, or a female who is unlikely to conceive, as indicated by meeting at least one of the following conditions:
a. Patient is a male.
b. Patient is a female of reproductive potential and either agrees to remain abstinent
(if this form of birth control is accepted by local regulatory agencies and review
committees as the sole method of birth control) or use (or have their partner use)
2 acceptable methods of birth control within the projected duration of the study.
c. Patient is a female who is not of reproductive potential and therefore eligible to
participate in this study without requiring the use of contraception. A female
patient who is not of reproductive potential is defined as: one who has either
1) reached natural menopause (defined as ≥6 months of spontaneous amenorrhea
with serum FSH levels in the postmenopausal range as determined by the
laboratory, or ≥12 months of spontaneous amenorrhea), 2) ≥6 weeks post
surgical hysterectomy, or bilateral oophorectomy with or without hysterectomy,
or 3) bilateral tubal ligation.
4. Patient is appropriate for lipid modifying therapy.
5. Patient must meet one of the following criteria based on NCEP ATP III risk
categorization: High risk (CHD or CHD risk equivalents e.g., diabetes, ≥2 risk factors with Framingham 10-year CHD risk >20%) on a statin with LDL-C <100 mg/dL
(<2.59 mmol/L) or intolerant to statins with LDL-C <120 mg/dL (<3.11 mmol/L),
Multiple risk (≥2 risk factors and Framingham 10-year CHD risk ≤20%) with
LDL-C <130 mg/dL (<3.37 mmol/L), Low risk (0-1 risk factors) with LDL-C <190 mg/dL (<4.92 mmol/L)
6. Patient has TG levels <500 mg/dL (<5.65 mmol/L). |
|
| E.4 | Principal exclusion criteria |
1. Patient is pregnant, breastfeeding, or expecting to conceive during the study including the 14-day post study follow-up.
2. 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.
6. Patient is currently participating in or has participated in a study with an investigational compound (non-lipid-modifying) within 30 days of Visit 1 or a lipid-modifying compound (investigational or marketed), within 6 weeks of Visit 1.
7. Patient has donated and/or received blood as follows: donated blood products or has had phlebotomy of >300 mL within 8 weeks prior to signing informed consent,
intends to give or receive blood products during the study, intends to donate more than 250 mL of blood products within 8 weeks following the last study visit.
8. Patient has the following exclusionary laboratory values at Visit 1
Creatinine >2.0 mg/dL (>177 micromol/L)
ALT (SGPT) >1.5 x ULN
AST (SGOT) >1.5 x ULN
CK >2 x ULN
9. Patient is at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse.
10. Patient is currently experiencing menopausal hot flashes.
11. Patient currently engages in, or during the study plans to engage, in vigorous exercise or an aggressive diet regimen in the opinion of the investigator.
12. Patient has chronic heart failure defined by the New York Heart Association (NYHA) Classes III or IV, uncontrolled cardiac arrhythmias, or poorly controlled hypertension (systolic blood pressure >160 mm Hg or diastolic >100 mm Hg).
13. Patient has Type 1 or Type 2 diabetes mellitus and meets one or more of the
following criteria: Patient is poorly controlled (HbA1C >8.5% at Visit 1), Patient is newly diagnosed (within 3 months of Visit 1), Patient has recently experienced repeated hypoglycemia or unstable glycemic control (within 3 months of Visit 1),
Patient is taking new or recently adjusted antidiabetic pharmacotherapy (with the
exception of ±10 units of insulin) within 3 months of Visit 1.
14. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia such as hyper- or hypothyroidism): Hyperthyroidism is defined as having a TSH below the central laboratory’s lower limit of the normal reference range (<0.30 mclU/ml) Hypothyroidism is defined as having a TSH >20% above the central laboratory’s
upper limit of the normal reference range (>6.0 mclU/ml)
15. Patient has nephrotic syndrome or other clinically significant renal disease.
16. Patient has active peptic ulcer disease within 3 months of Visit 1.
17. Patient has had an episode of gout within 1 year of Visit 1, unless patient is currently taking allopurinol.
18. Patient has a history of hypersensitivity or allergic reaction to niacin or niacincontaining products.
19. Patient has history of myocardial infarction, stroke, coronary artery bypass surgery or other revascularization procedure, unstable angina or angioplasty within 3 months of Visit 1.
20. Patient has arterial bleeding.
21. Patient has history of ileal bypass, gastric bypass, gastric banding or other significant condition associated with malabsorption or rapid weight loss within 18 months of Visit 1.
22. Patient has active or chronic hepatobiliary or hepatic disease.
23. Patient is HIV positive as assessed by medical history.
Prohibited Concomitant Medications
24. Patient is currently taking or has taken niacin >50 mg once daily within 6 weeks of Visit 1.
25. Patient has had a change to type or dose of LMT regimen within 6 weeks of Visit 1.
26. Patient is taking a statin (or statin containing product) and fibrate concomitantly at Visit 1
27. Patient is Chinese and is on simvastatin 80 mg or a product containing simvastatin 80 mg at Visit 1
28. Patient is taking long-acting NSAID including naproxen, etodolac, salsalate, and
diclofenac at Visit 1.
29. Patient is taking Aspirin greater than 100mg per day at Visit 1.
30. Patient is receiving treatment with systemic corticosteroids (intravenous, injected, and oral steroids) OR systemic anabolic agents.
31. Patient consumes more than 3 alcoholic drinks on any given day or more than 14
drinks per week. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Number of days per week with GFSS≥4 during weeks 21 to 32. |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 75 |
| 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 | 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 | 7 |
| E.8.9.1 | In the Member State concerned days | 15 |
| 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 | 15 |
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