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

• Register: EUCTR
• Last refreshed on: 27 January 2014
• Main ID: EUCTR2012-001363-70-NL
• Date of registration: 12/09/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Study to assess the safety and efficacy of AMG-145 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. LAPLACE - 2 LDL-C Assessment w/ PCSK9 MonoclonaL Antibody Inhibition Combined with Statin ThErapy
• Date of first enrolment: 24/10/2012
• 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: no Placebo: yes Other: yes Other specify the comparator: Ezetimibe Number of treatment arms in the trial: 24

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Hong Kong, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Russian Federation, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, 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
• 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 of Protocol) at screening must have a fasting LDL-C at screening of = 80 mg/dL (2.1 mmol/L) as determined by central laboratory
•Negative pregnancy test, AST and ALT = 2 times ULN, CK = 3 times ULN as determined by central laboratory at the end of the lipid stabilization period
• 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 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.
•Subject, who in the opinion of the investigator, requires maximal statin therapy
•Personal or family history of hereditary muscular disorders
•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 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 (LLN) or > 1.5 times the upper limit of normal (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 in the past year, 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

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: 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

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

Product Name: Atorvastatin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: atorvastatin
CAS Number: 134523-00-5
Other descriptive name: atorvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Atorvastatin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: atorvastatin
CAS Number: 134523-00-5
Other descriptive name: atorvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-

Product Name: rosuvastatin
Pharmaceutical Form: Tablet
INN or Proposed INN: rosuvastatin
CAS Number: 287714-41-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: rosuvastatin
Pharmaceutical Form: Tablet
INN or Proposed INN: rosuvastatin
CAS Number: 287714-41-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Name: rosuvastatin
Pharmaceutical Form: Tablet
INN or Proposed INN: rosuvastatin
CAS Number: 287714-41-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Product Name: simvastatin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: simvastatin
CAS Number: 79902-63-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 administered every 2 weeks (Q2W) and monthly (QM) 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 QM 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 QM used in combination with a statin compared to placebo or ezetimibe, on change from baseline in LDL-C, and percent change from baseline in non-high-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, very low-density lipoprotein cholesterol (VLDL-C), and HDL-C in subjects with primary hypercholesterolemia and mixed dyslipidemia
• 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)

Timepoint(s) of evaluation of this end point: 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

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 Outcome(s)

Secondary end point(s): Co-secondary endpoints of the means at weeks 10 and 12 and at week 12 for: Tier 1 endpoints
• Change from baseline in LDL-C
• 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 endpoints
• LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L])
• 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 endpoints
• Change from baseline in LDL-C
• 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 endpoints
• LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L])
• 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)

2012-001363-70-ES

20110115

Source(s) of Monetary Support

Amgen Inc