Study to access whether AMG 145, in people with dyslipidemia, who cannot tolerate an effective dose of a statin, causes any side effects and to confirm that treatment with AMG 145 will lower LDL-cholesterol and increase HDL-cholesterol. To do this, AMG 145 will be compared with ezetimibe which is a cholesterol-lowering medication used to help patients manage cholesterol levels.

• Register: EUCTR
• Last refreshed on: 27 January 2014
• Main ID: EUCTR2012-001364-30-NL
• Date of registration: 13/09/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Study to access whether AMG 145, in people with dyslipidemia, who cannot tolerate an effective dose of a statin, causes any side effects and to confirm that treatment with AMG 145 will lower LDL-cholesterol and increase HDL-cholesterol. To do this, AMG 145 will be compared with ezetimibe which is a cholesterol-lowering medication used to help patients manage cholesterol levels.
• Scientific title: Title: A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor. GAUSS-2 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects
• Date of first enrolment: 30/10/2012
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001364-30
• 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: 4

Countries of recruitment

Australia, Belgium, Canada, Denmark, France, Germany, Hong Kong, Japan, Netherlands, Poland, South Africa, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
•Subject has provided informed consent.
•Male or female = 18 to = 80 years of age at signing of informed consent
•Subject not on a statin or on a low dose statin as defined below. For statins not listed, the maximal total weekly dose is 7 times the smallest available tablet size. For the listed statins below, the following maximum total prescribed weekly dosages apply
a) atorvastatin - 70 mg or less
b) simvastatin - 140 mg or less
c) pravastatin - 140 mg or less
d) rosuvastatin - 35 mg or less
e) lovastatin - 140 mg or less
f) fluvastatin - 280 mg or less
•Subject not at LDL-C goal as evidenced by their NCEP ATP III risk category (see Appendix D) and the following LDL-C levels by central laboratory at screening:
a) Fasting LDL-C = 100 mg/dL (2.6 mmol/L) for subjects with diagnosed CHD or are CHD risk equivalent or
b) Fasting LDL-C = 130 mg/dL (3.4 mmol/L) for subjects without diagnosed CHD or risk equivalent and 2 or more risk factors or
c) Fasting LDL-C = 160 mg/dL (4.1 mmol/L) for subjects without diagnosed CHD or risk equivalent and with 1 or no risk factors
d) Fasting LDL-C = 190 mg/dL (4.9 mmol/L) for subjects without
diagnosed CHD or risk equivalent and with no risk factors
•Subject has a history of statin intolerance as evidenced by both of the following (per subject or physician report):
a) Tried at least 2 statins and was unable to tolerate any dose or
increase statin dose above the total weekly maximum doses listed inSection 4.1.3 due to intolerable myopathy, ie, myalgia (muscle pain, ache, or weakness without CK elevation), myositis (muscle symptoms with increased CK levels), or rhabdomyolysis (muscle symptoms with marked CK elevation)
b) Symptoms resolved or improved when statin dose was decreased or discontinued
•Lipid lowering therapy has been stable prior to LDL-C screening for at least 4 weeks if currently on a statin and/or bile-acid sequestering resin and/or stanol; if subject is on ezetimibe at start of screening, ezetimibe must be discontinued for = 4 weeks before LDL-C screening
•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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
•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 past 3 months prior to randomization
•Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 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 serum 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, or prescription lipid-regulating drugs (eg, fibrates and derivatives) other than statins, ezetimibe, bile-acid sequestering resin, or stanols and stanol esters
•Subject has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to LDL-C screening, such as: anacetrapib, dalcetrapib or evacetrapib.
•Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (eg, IV,intramuscular [IM], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted)
•Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) < 1.0 time the lower limit of normal or >1.5 times the ULN, respectively, at screening
•Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 at screening
•Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as determined by central laboratory analysis at screening
•CK > 3 times the ULN at screening
•Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator
•Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months prior to randomization
•Unreliability as a study participant based on the investigator's (or designee’s) knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
•Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
•Female subject who has either (1) not used at least 1 highly effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal;
-menopause is defined as 12 months of spontaneous and continuous amenorrhea in a female = 55 years old or 12 months of spontaneous and continuous amenorrhea with a follicle-stimulating

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

Health Condition(s) or Problem(s) studied

Dyslipidemia
MedDRA version: 14.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861
MedDRA version: 14.1 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 100000004861

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

Intervention(s)

Product Name: AMG 145
Pharmaceutical Form: Solution for injection in pre-filled pen
Current Sponsor code: AMG 145
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Solution for injection in pre-filled pen
Route of administration of the placebo: Subcutaneous use

Trade Name: ZETIA® (ezetimibe) Tablets
Product Name: Ezetimibe
Pharmaceutical Form: Tablet
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
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic subjects unable to tolerate an effective dose of a statin.

Primary end point(s): Co-Primary Endpoints:
•Mean percent change from baseline in LDL-C at weeks 10 and 12
• Percent change from baseline in LDL-C at week 12

Secondary Objective: •To evaluate safety and tolerability of SC AMG 145 Q2W and QM, compared with ezetimibe, in hypercholesterolemic subjects unable to tolerate an effective dose of a statin
•To evaluate effect of 12 weeks of SC AMG 145 Q2W and QM compared with ezetimibe, on percent change from baseline in LDL-C in hypercholesterolemic subjects unable to tolerate an effective dose of a statin and not receiving any lipid regulating medications at study entry
• To assess the effects of 12 weeks SC AMG 145 Q2W and QM, compared with ezetimibe, on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) in hypercholesterolemic subjects unable to tolerate an effective dose of a statin
Refer pg 18 of protocol for remaining objectives

Secondary Outcome(s)

Secondary end point(s): Co-Secondary Efficacy Endpoints
Co-secondary endpoints of the means at weeks 10 and 12 and at week 12 for:
Tier 1
•Change from baseline in LDL-C
• LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L])
•Percent change from baseline in non-HDL-C
• Percent change from baseline in ApoB
•Percent change from baseline in the total cholesterol/HDL-C ratio
• Percent change from baseline in ApoB/ApoA1 ratio
Tier 2
• Percent change from baseline in Lp(a)
• Percent change from baseline in triglycerides
• Percent change from baseline in HDL-C
• Percent change from baseline in VLDL-C

Timepoint(s) of evaluation of this end point: Co-secondary endpoints of the means at weeks 10 and 12 and at week 12 for:
Tier 1
•Change from baseline in LDL-C
• LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L])
•Percent change from baseline in non-HDL-C
• Percent change from baseline in ApoB
•Percent change from baseline in the total cholesterol/HDL-C ratio
• Percent change from baseline in ApoB/ApoA1 ratio
Tier 2
• Percent change from baseline in Lp(a)
• Percent change from baseline in triglycerides
• Percent change from baseline in HDL-C
• Percent change from baseline in VLDL-C

Secondary ID(s)

20110116

2012-001364-30-ES

Source(s) of Monetary Support

Amgen Inc