Study to assess the tolerability and efficacy of AMG 145 in patients with hypercholesterolemia unable to tolerate an effective dose of a statin.

• Register: EUCTR
• Last refreshed on: 19 November 2012
• Main ID: EUCTR2011-001529-26-SE
• Date of registration: 17/06/2011
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Study to assess the tolerability and efficacy of AMG 145 in patients with hypercholesterolemia unable to tolerate an effective dose of a statin.
• Scientific title: A Randomized, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C, Compared with Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor
• Date of first enrolment: 20/07/2011
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001529-26
• 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: no Number of treatment arms in the trial: 5

Countries of recruitment

Australia, Belgium, Canada, Denmark, Finland, Spain, Sweden, 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 = 75 years of age
- Subject not on a statin or on a low dose statin - as defined by a maximal total weekly dose corresponding to 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 -1 40 mg or less
f) fluvastatin - 280 mg or less
- Subject not at LDL-C goal as evidenced by their NCEP ATP III risk category and the following LDL-C levels by central laboratory at screening:
a) Fasting LDL-C = 100 mg/dL for subjects with diagnosed CHD or are CHD risk equivalent or
b) Fasting LDL-C = 130 mg/dL for subjects without diagnosed CHD or risk equivalent and 2 or more risk factors or
c) Fasting LDL-C = 160 mg/dL for subjects without diagnosed CHD or risk equivalent and with 1 or no risk factors
- Subject has a history of statin intolerance as evidenced by both of the following (per subject or physician report):
- Tried at least two statins and was unable to tolerate any dose or increase statin dose above the total weekly maximum doses listed in Section 4.1.3 due to intolerable myalgia (muscle pain, soreness, weakness, or cramps) or myopathy (myalgia plus a raised CK)
- Symptoms resolved or improved when statin dose was decreased or discontinued
- Lipid lowering therapy has been stable prior to enrollment for at least:
a) 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
b) 12 weeks if taking any other lipid modifying agents (eg niacin, fibrates and derivative, etc.)
- Fasting triglycerides = 400 mg/dL 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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
- NYHA III or IV heart failure, or known left ventricular ejection fraction < 30%
- Uncontrolled 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 3 months prior to randomization
- Planned cardiac surgery or revascularization within 20 weeks of screening
- Type 1 diabetes or newly diagnosed (within 3 months of randomization) type 2 diabetes, or poorly controlled type 2 diabetes (HbA1c > 8.5%)
- Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg, confirmed with repeat measurement
- Subject has taken during > 2 weeks in the last 3 months prior to LDL-C screening: prescription lipid-regulating drugs other than statins or ezetimibe, such as fibrates and derivatives, bile-acid sequestering resins; red yeast rice, niacin (> 200 mg/day), or omega-3 fatty acids (>1000 mg/day)
- Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: cyclosporine, systemic steroids (IV, intramuscular [IM], or PO), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted)
- Hyperthyroidism or hypothyroidism as defined by TSH below 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, confirmed by a repeat measurement at least 1 week apart
- 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
- Current therapeutic anticoagulation with vitamin K antagonist (eg, warfarin), heparin, low-molecular weight heparin, direct thrombin inhibitor, or Factor Xa inhibitor
- 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 is not willing to use at least one highly effective method of birth control during treatment and for an additional 15 weeks after the end of treatment unless subject is sterilized or postmenopausal; postmenopausal is defined as 12 continuous months of spontaneous amenorrhea; highly effective methods include birth control pills, shots, implants, or patches, intrauterine devices (IUDs), sexual activity with a male partner who has had a vasectomy, condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide
- Subject is pregnant or breast feeding, or

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]

Hypercholesterolaemia
MedDRA version: 13.1 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: AMG 145
Product Code: AMG 145
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 145
Other descriptive name: AMG 145
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: Ezetrol
Product Name: Ezetimibe
Product Code: 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-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to week 12

Primary end point(s): 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, 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 HMG CoA reductase inhibitor.

Secondary Objective: • To evaluate the safety and tolerability of 3 doses of AMG 145 SC alone, a high dose of AMG 145 SC with ezetimibe, or ezetimibe alone, in hypercholesterolemic subjects unable to tolerate an effective dose of a HMG-CoA reductase inhibitor
• To assess the effects of 12 weeks of AMG 145 SC alone, AMG 145 SC with ezetimibe, or ezetimibe alone, on absolute change in LDL-C, and percent change in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/apolipoprotein A-1 (ApoA1) ratio in hypercholesterolemic subjects unable to tolerate an effective dose of a HMG CoA reductase inhibitor
• To characterize pharmacokinetics of AMG 145 following SC injection in hypercholesterolemic subjects unable to tolerate an effective dose of a HMG CoA reductase inhibitor

Secondary Outcome(s)

Secondary end point(s): - Absolute change from baseline in LDL-C 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

Timepoint(s) of evaluation of this end point: - Absolute change from baseline in LDL-C at week 12: from baseline to week 12
- Percent change from baseline in non-HDL-C at week 12: from baseline to week 12
- Percent change from baseline in ApoB at week 12: from baseline to week 12
- Percent change from baseline in the total cholesterol/HDL-C ratio at week 12: from baseline to week 12
- Percent change from baseline in ApoB/ApoA1 ratio at week 12: from baseline to week 12

Secondary ID(s)

20090159

2011-001529-26-ES

Source(s) of Monetary Support

Amgen Inc