Study to assess the safety and efficacy of AMG-145 on LDL-cholesterol, in combination with Statin therapy in patients with high blood cholesterol or high concentration of lipids in the blood.

• Register: EUCTR
• Last refreshed on: 23 December 2013
• Main ID: EUCTR2012-001363-70-IT
• Date of registration: 25/09/2012
• Prospective Registration: No
• Primary sponsor: AMGEN INC.
• Public title: Study to assess the safety and efficacy of AMG-145 on LDL-cholesterol, in combination with Statin therapy in patients with high blood cholesterol or high concentration of lipids in the blood.
• Scientific title: A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
• Date of first enrolment: 13/09/2012
• Target sample size: 1700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001363-70
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: yes Other specify the comparator: ezetimibe Number of treatment arms in the trial: 24

Countries of recruitment

Argentina, Australia, Brazil, Canada, Czech Republic, Denmark, Germany, Hong Kong, Hungary, Italy, Korea, Democratic People's Republic of, Mexico, Netherlands, Russian Federation, South Africa, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Dip.to Regolatorio
• Affiliation: Amgen Dompe' SpA

• Name: Dip.to Regolatorio
• Affiliation: Amgen Dompe' SpA

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female = 18 to = 80 years of age • Subjects not taking a statin at screening must have a fasting LDL-C of at least 150 mg/dl (4.0 mmol/L) as determined by central laboratory • Subjects already on a non-intensive statin (see Appendix D) at screening must have a fasting LDL-C at screening of = 100 mg/dL (2.6 mmol/L) as determined by central laboratory • Subjects already on a intensive statin (see Appendix D) at screening must have a fasting LDL-C at screening of = 80 mg/dL (2.1 mmol/L) as determined by central laboratory • Fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory at screening
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion criteria:
•Current or prior history of statin intolerance, or any intolerance to rosuvastatin, atorvastatin, or simvastatin. •NYHA III or IV heart failure, or last known left ventricular ejection fraction < 30% •Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to randomization •Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 6 months prior to randomization •Planned cardiac surgery or revascularization •Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c > 8.5%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting plasma glucose = 126 mg/dL [7.0 mmol/L] or HbA1c = 6.5%) without prior diagnosis of diabetes •Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg •Subject has taken in the last 6 weeks prior to LDL-C screening red yeast rice, > 200 mg/day niacin, > 1000 mg/day omega-3 fatty acids ( DHA and EPA combined), stanols or prescription lipid-regulating drugs (eg, bileacid sequestering resins, fibrates and derivatives) other than statins and ezetimibe - Subject, who in the opinion of the investigator, requires maximal statin therapy - Personal or family history of hereditary muscular disorders - Known sensitivity to any of the active substances or their excipients to be administered during dosing. Please see the protocol for furtehr exclusion criteria


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Primary Hypercholesterolemia and Mixed Dyslipidemia
MedDRA version: 15.1 Level: PT Classification code 10058108 Term: Dyslipidaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 15.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: AMG145
Product Code: NA
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG145
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: ZETIA (ezetimibe) tablets
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: EZETIMIBE
CAS Number: 163222-33-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the percent change from baseline in LDL-C at week 12.

Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 administered every 2 weeks (Q2W) and every 4 weeks (Q4W) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in subjects with primary hypercholesterolemia and mixed dyslipidemia.

Secondary Objective: • To evaluate the safety and tolerability of SC AMG 145 Q2W and Q4W used in combination with a statin, compared with placebo or ezetimibe, in subjects with primary hypercholesterolemia and mixed dyslipidemia • To assess the effects of 12 weeks of SC AMG 145 Q2W and Q4W used in combination with a statin compared to placebo or ezetimibe, on change from baseline in LDL-C, and percent change from baseline in nonhigh- density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, ApoB/ Apolipoprotein A-1 (ApoA1) ratio lipoprotein (a) [Lp(a)], triglycerides and HDLC in subjects with primary hypercholesterolemia and mixed dyslipidemia Please see the Protocol for furhte secondary objectives

Timepoint(s) of evaluation of this end point: At week 12

Secondary Outcome(s)

Secondary end point(s): Tier 1 endpoints • Change from baseline in LDL-C at week 12 • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) at week 12 • Percent change from baseline in non-HDL-C at week 12 • Percent change from baseline in ApoB at week 12 • Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 • Percent change from baseline in ApoB/ApoA1 ratio at week 12 Tier 2 endpoints • Percent change from baseline in Lp(a) at week 12 • Percent change from baseline in triglycerides at week 12

Timepoint(s) of evaluation of this end point: Secondary Efficacy Endpoints • Change from baseline in LDL-C at week 12 • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) at week 12 • Percent change from baseline in non-HDL-C at week 12 • Percent change from baseline in ApoB at week 12 • Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 • Percent change from baseline in ApoB/ApoA1 ratio at week 12 • Percent change from baseline in Lp(a) at week 12 • Percent change from baseline in triglycerides at week 12

Secondary ID(s)

20110115

2012-001363-70-ES

Source(s) of Monetary Support

Amgen Inc