| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type II Diabetes Mellitus |
|
| 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 | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| 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 evaluate the LDL-C lowering efficacy of ER niacin/laropiprant (1 to 2g) compared with placebo in patients with Type 2 diabetes. |
|
| E.2.2 | Secondary objectives of the trial |
1. In patients with Type 2 Diabetes, to assess:
Percent change in HDL-C, Triglycerides (TG), TC/HDL-C ratio, LDL-C/HDL-C ratio, Apo B, Apo A-1.
Safety and tolerability after 12 weeks of treatment with ER niacin/laropiprant (1 to 2g) compared to placebo.
2. In patients with Type 2 Diabetes, to assess change in HBA1c and FPG.
Percent of patients requiring Anti-diabetic medication changes
after 36 weeks of treatment with ER niacin/laropiprant (1 to 2g) compared to placebo.
3. In patients with Type 2 Diabetes, to assess change in HBA1c and FPG.
Percent of patients requiring Anti-diabetic medication changes
after 36 weeks of treatment with ER niacin/laropiprant (1 to 2g) compared to placebo.
4. In patients with Type 2 Diabetes, to perform a detailed lipoprotein analysis based on:
A variety of Apoproteins (see Appendix 6.1)
Beta-Quant parameters (see Appendix 6.1)
VAP
Quest Ion Mobility
after 36 weeks of treatment with ER niacin/laropiprant (1 to 2g) compared to placebo.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient is male or female and 18 to 80 years of age on day of signing informed
consent.
2. Patient with a confirmed diagnosis of Type 2 Diabetes Mellitus.
3. Patient will maintain diet consistent with ADA dietary guidelines or similar glucose
and cholesterol lowering diet for the duration of the study.
4. If patient is receiving statin therapy, they should be on a stable dose for at least 3
weeks prior to Visit 1 (Week -1).
5. Patient is on a stable dose of any antidiabetic pharmacotherapy (with the exception of
± 10 units of insulin) for 3 months prior to Visit 1 (Week -1).
NOTE: Changes to antidiabetic medications will be permitted during the study.
6. LDL-C is <115 mg/dL and >70 mg/dL at Visit 1 (Week -1).
NOTE: One immediate retest is allowed for patient with LDL-C value that is >10%
outside the protocol specified acceptable inclusion range.
7. A female patient who is of reproductive potential agrees to remain abstinent or use (or
have their partner use) 2 acceptable methods of birth control for the duration of the
study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm
with spermicide, contraceptive sponge, condom, vasectomy.
NOTE: Female patients who have reached menopause*, undergone hysterectomy,
bilateral oophorectomy, or bilateral tubal ligation are eligible without the use of
contraceptives.
* Menopause is defined as 43 years of age and (1) no menses for >1 year and follicle
stimulating hormone (FSH) levels elevated into postmenopausal range (defined by central
lab) OR (2) no menses for at least 3 years.
NOTE: Patients on cyclical hormonal contraceptives are not eligible. However,
continuous hormone replacement therapy for post-menopausal women or continuous
hormonal contraceptives are allowed provided that the patient has been on a stable
regimen for >6 weeks prior to visit 1 and agrees to remain on this regimen throughout the
study. Continuous hormonal contraceptive is not considered as one of the two acceptable
methods for birth control.
8. Triglyceride concentrations 500 mg/dL at Visit 1 (Week-1).
NOTE: One immediate retest is allowed for patient with TG value that is 15%
outside acceptable inclusion range.
|
|
| 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.
3. Female patient is expecting to donate eggs during the study, including the 14 day
follow-up.
4. Patient has a history of current evidence of any condition, therapy, or lab abnormality
that might confound the results of the study, interfere with the patient’s participation
for the full duration of the study, or is not in the best interest of the patient to
participate.
5. Patient is unlikely to adhere to the study procedures, keep appointments, or is
planning to relocate during the study.
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.
- a lipid-modifying compound (investigational or marketed), within 6 weeks of
Visit 1 (fibrate within 8 weeks)
7. Patient has taken torcetrapib alone or in combination and the last dose was within 1
year of Visit 1.
8. Patient has donated blood products or has had phlebotomy of >300 mL within 8
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.
9. Patient has the following exclusionary laboratory values at Visit 1 (See Table 3-3 for
retest guidance); Creatinine >2.0 mg/dL, ALT (SGPT) >1.5 x ULN, AST (SGOT) >1.5 x ULN, CK >2 xULN.
10. Patient has HbA1c at screening or Visit 1 >8.5% or is newly diagnosed with Type 2
Diabetes Mellitus (within 3 months of Visit 1).
11. 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.
12. Patient currently engages, or during the study plans to engage, in vigorous exercise or
an aggressive diet regimen.
Prohibited Medical Conditions
13. Patient has uncontrolled endocrine or metabolic disease known to influence serum
lipids or lipoproteins (ie: secondary causes of hyperlipidemia, such as hypothyroidism
or hyperthyroidism.
14. Patient has nephrotic syndrome or other clinically significant renal disease.
15. Patient has chronic heart failure defined by New York Heart Association (NYHA)
Classes III or IV.
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 taking
allopurinol.
18. Patient has a history of hypersensitivity or allergic reaction to niacin or niacin-
containing products.
19. Patient has uncontrolled/unstable cardiac arrhythmias.
20. Patient has history of myocardial infarction, stroke, coronary artery bypass surgery or
other or other revascularization procedure, unstable angina or angioplasty within 3
months of Visit 1.
21. Patient has unstable hypertension (sitting systolic blood pressure >160 mm Hg or
diastolic >100 mm Hg) at Visit 1. Investigators are encouraged to maximize blood
pressure control according to current local guidelines.
22. Patient has history of ileal bypass, gastric bypass or other significant condition
associated with malabsorption.
23. Patient has active or chronic hepatobiliary or hepatic disease.
24. Patient is HIV positive.
Prohibited Medications
25. Patient is on Cholestin™ within 6 weeks prior to Visit 2.
26. Patient is taking a statin and fibrate concomitantly.
27. The daily intake of EPA+DHA > 200 mg/day (for example, 1g of cod liver oil
contains 0.19g of EPA+DHA, and does not exceed the RDA for vitamins A and D).
28. Patient is currently taking niacin 50 mg/day.
29. Patient has initiated therapy with orlistat, subutramine, or other anti-obesity
medication within 3 months prior to randomization.
30. Patient is currently taking treatment with psyllium, phytosterol margarines, other
fiber-based laxatives, and/or OTC therapies known to affect serum lipid levels and
has not been on a stable regimen for at least 6 weeks or does not agree to remain
stable for the duration of the study.
31. Patient is a woman currently taking cyclical hormonal contraceptives or intermittent
use of HRTs (e.g., estradiol, medroxyprogesterone, progesterone).
32. Patients receiving treatment with systemic corticosteroids (intravenous, injected, and
oral steroids) OR systemic anabolic agents.
33. Patient consumes more than 2 alcoholic drinks per day.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percent change from baseline in LDL-C at Week 12.
Secondary lipid endpoints are the percent change from baseline in HDL-C and other lipid
parameters (except TG, hsCRP and Lp(a)) at Week 12.
|
|
| 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 | Information not present in EudraCT |
| 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) | 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 | 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 | 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| 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 | Yes |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
Print
