| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Patients With Primary hypercholesterolemia or
Mixed Dyslipidemia |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10047065 |
|
| 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 |
Objective: To evaluate the LDL-C lowering efficacy of the addition of ER
niacin/laropiprant (1 to 2 g) to simvastatin or atorvastatin (pooled across statin and doses)
compared with doubling the dose of simvastatin or atorvastatin (pooled) in patients with
primary hypercholesterolemia or mixed dyslipidemia who are not at their NCEP ATP III
LDL-C goal. |
|
| E.2.2 | Secondary objectives of the trial |
In patients with primary hypercholesterolemia or mixed dyslipidemia who
are not at their target LDL-C goal, to assess:
Percent change in HDL-C
Percent change in Triglycerides (TG)
Percent change in TC/HDL-C ratio
Percent change in LDL-C/HDL-C ratio
Percent change in Apo B
Percent change in Apo A-I
Safety and tolerability
After 12 weeks of treatment with ER niacin/laropiprant (1 to 2 g) plus simvastatin or
atorvastatin (pooled across statin doses) compared to doubling the baseline simvastatin or
atorvastatin pooled doses. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Patient is male or female, between 18 to 80 years of age on day of signing informed
consent.
2. 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. An acceptable method of birth control is defined as: 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.
Patient needs to meet one of the following:
is on a stable dose of simvastatin (10 to 20 mg) or atorvastatin (10 mg) for at least
6 weeks prior to Visit 1 (Week -2) OR
is on any dose of lovastatin, pravastatin, or fluvastatin at screening visit (Week -6)
OR
is naïve to all lipid-lowering therapy for at least 3 month prior to screening visit
(Week -6).
4. Naïve patients (not on any lipid lowering therapy 3 months prior to screening visit)
should meet one of the following at the screening visit to enter the study:
High risk naïve patient (CHD/CHD risk equivalent including diabetes) has an
LDL-C ≥140 mg/dL and < 190 mg/dL (3.6 and 5.0 mmol/L).
Multiple risk (≥2 RF) naïve patient has an LDL-C ≥180 mg/dL and < 240 mg/dL
(4.7 and 6.2 mmol/L).
Low risk (0 to 1 RF) naïve patient has an LDL-C ≥220 mg/dL (5.7 mmol/L).
5. Patient with diabetes mellitus must have a confirmed diagnosis and been on a stable
dose of antidiabetic pharmacotherapy for 3 months prior to Visit 1.
6. All patients must meet one of the following criteria (based on NCEP ATP III
Guidelines) at Visit 1 (see Appendix 6.5 to determine patient risk category):
High Risk
Patient is high risk (CHD/CHD risk equivalent including diabetes) with an LDL-C
>100 mg/dL and ≤130 mg/dL (2.7 mmol/L and 3.4 mmol/L).
0524A_067-00_ProtCore VERSION 7.1 APPROVED 09-Apr-2007
Non-U.S. IND, Ex-U.S. Study Restricted Confidential – Limited Access
Multiple Risk
Patient has multiple risk factors (≥2 RF) with an LDL-C >130 mg/dL and
≤160 mg/dL (3.4 mmol/L and 4.1 mmol/L).
Low Risk
Patient is low risk (0 to 1 RF) with an LDL-C >160 mg/dL and ≤190 mg/dL
(4.1 mmol/L and 5.0 mmol/L). |
|
| E.4 | Principal exclusion criteria |
0524A_067-00_ProtCore VERSION 7.1 APPROVED 09-Apr-2007
Non-U.S. IND, Ex-U.S. Study Restricted Confidential – Limited Access
Patient is pregnant, breast-feeding, or expecting to conceive during the study
including the 14-day poststudy 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.
Note: Patients with a history of malignancy ≤5 years may be allowed in the study if,
in the opinion of the investigator and Sponsor, they are highly unlikely to relapse
during the duration of the study.
3. Female patient is expecting to donate eggs during the study, including 14-day follow-up.
4. Patient has a history or 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 previously participated in a study with:
an investigational compound within 30 days of Visit 1.
an investigational lipid-modifying compound within 6 weeks of Visit 1 (an
investigational fibrate within 8 weeks).
Product: MK-0524A 8
Protocol/Amendment No.: 067-00
7. Patient has taken torcetrapib alone or in combination and the last dose was within
1 year of Visit 1.
Note: To participate in the study, patients who previously participated in a torcetrapib
trial must provide documentation that he/she did not receive torcetrapib or that the
last dose of torcetrapib was greater than 1 year of Visit 1.
8. 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.
9. Patient has the following exclusionary laboratory values at Visit 1 (see Table 3-2 for
retest guidelines).
Creatinine >2.0 mg/dL (177 micromol/L)
ALT (SGPT) >1.5 x ULN
AST (SGOT) >1.5 x ULN
CK >2 x ULN
10. Patient with Type 1 or Type 2 diabetes mellitus and:
is poorly controlled (HbA1C at Screening >8.5%)
is newly diagnosed (within 3 months of Visit 1)
has recently experienced repeated hypoglycemia or unstable glycemic control
is taking new or recently adjusted anti-diabetic pharmacotherapy (with the exception
of ±10 units of insulin) 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.
13. Patient has <80% compliance with dosing during the statin run-in period and in the
opinion of the investigator, compliance will not improve following proper counsel
during the active study dosing period. |
|
| 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. |
|
| 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 | 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 | 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) | 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.8.5 | 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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