Study to assess the tolerability and efficacy of AMG-145 monotherapy in patients with hypercholesterolemia

• Register: EUCTR
• Last refreshed on: 3 December 2012
• Main ID: EUCTR2011-001544-30-DK
• Date of registration: 29/06/2011
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Study to assess the tolerability and efficacy of AMG-145 monotherapy in patients with hypercholesterolemia
• Scientific title: A Randomized, Placebo and Ezetimibe Controlled, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Hypercholesterolemic Subjects With a 10 Year Framingham Risk Score of 10% or Less - MENDEL
• Date of first enrolment: 03/08/2011
• Target sample size: 405
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001544-30
• 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: no Number of treatment arms in the trial: 9

Countries of recruitment

Australia, Belgium, Canada, Denmark, Germany, South Africa, 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
- NCEP ATP III Framingham risk score of 10% or less
- Fasting LDL-C = 100 mg/dL and (2.6 mmol/L) < 190 mg/dL (4.9 mmol/L) by central laboratory at 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 238
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 167

Exclusion criteria:
- History of coronary heart disease (CHD) or CHD risk-equivalent disease as per NCEP ATP III
- NYHA II - IV heart failure
- Uncontrolled seriuous 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
- Diabetes mellitus or fasting plasma glucose at screening
= 126 mg/dL (7.0 mmol/L) or HbA1c = 6.5%
- Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg, confirmed with repeat measurement
- Subject has taken lipid-regulating drugs in the last 3 months prior to LDL-C screening, such as HMG CoA reductase inhibitors, psyllium preparations including Metamucil® (> 2 tbs. per day), fibrates and derivatives, cholesterol absorption inhibitors such as ezetimibe, bile-acid sequestering resins; red yeast rice, niacin (> 200 mg per day), and omega-3 fatty acid (> 300 mg per day) (eg, docosahexaenoic acid
[DHA] and eicosapentaenoic acid [EPA]). Subjects currently on lipid lowering therapy when study enrollment begins may not be screened or randomized at any time in the future
- Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (e.g, 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 thyroid stimulating hormone (TSH) below the lower limit of normal (LLN) 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, confirmed by a repeat measurement at least 1 week apart
- 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, confirmed by a repeat measurement at least 1 week apart
- 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 (Note: anti-platelet agents [eg, aspirin,
clopidogrel, prasugrel, ticagrelor, dipyridamole] are permitted)
- 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 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; highly effective methods of birth control n

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

Health Condition(s) or Problem(s) studied

Hypercholesterolaemia
MedDRA version: 14.0 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders

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

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)

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

Secondary Objective: - To evaluate the safety and tolerability of 6 dose regimens of SC AMG 145 monotherapy, compared with placebo and with ezetimibe, in subjects with hypercholesterolemia and a 10 year Framingham risk score of 10% or less
- To evaluate the effects of 12 weeks of SC AMG 145 monotherapy, ezetimibe, and placebo 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 subjects with hypercholesterolemia and a 10 year Framingham risk score of 10% or less
- To characterize pharmacokinetics of AMG 145 following SC injection in subjects with hypercholesterolemia

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

Main Objective: To evaluate the effect of 12 weeks of subcutaneous AMG 145 every-2-weeks (Q2W) or every-4-weeks (Q4W), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) when used as monotherapy in hypercholesterolemic subjects with a 10 year Framingham risk score of 10% or less.

Secondary Outcome(s)

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 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

Secondary ID(s)

20101154

Source(s) of Monetary Support

Amgen Inc