Hyperlipidemia or mixed dyslipidemia in Diabetic Subjects
Conditions
Interventions
Product Name: Evolocumab
Product Code: Evolocumab
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Evolocumab
Current Sponsor code: Evolocumab
Other descriptive name:
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subject has provided written informed consent. 2) Male or female, = 18 to = 80 years of age at signing of informed consent. 3) Type 2 diabetes, defined as receiving pharmacologic treatment for type 2 diabetes for = 6 months prior to screening, with stable diabetes therapy prior to randomization to IP and not expected to change during the duration of study participation. Stable diabetes therapy is defined as no new agents added, no dose change of any oral antihyperglycemic drug within 2 months, and daily insulin dose not changed by > 25% and > 25 units within 1 month prior to randomization 4) Lipid-lowering therapy status (eg, not receiving any therapy or receiving any statin, ezetimibe, bile-acid sequestering resin, stanols, probucol, omega 3 fatty acids or niacin) must be unchanged for = 4 weeks prior to LDL-C screening. 5) Subjects receiving statin therapy at screening must have a fasting LDL-C at screening of = 100 mg/dL (2.6 mmol/L) as determined by central laboratory. 6) Subjects not receiving statin therapy at screening must have a fasting LDL-C at screening of = 130 mg/dL (3.4 mmol/L) as determined by central laboratory. 7) 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 700 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1) Receiving 20 mg atorvastatin QD monotherapy for approximately 16 weeks is medically contraindicated or inappropriate based on opinion of investigator. 2) NYHA III or IV heart failure, or last known left ventricular ejection fraction 10.0 % at screening and at lipid stabilization or not on stable pharmacologic therapy for type 2 diabetes. Stable therapy is defined as no new agents added, no dose change of any oral antihyperglycemic drug within 2 months, and daily insulin dose not changed by > 25% and > 25 units within 1 month prior to randomization. 7) Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg 8) Subject is unwilling or unable to discontinue between start of lipid stabilization with 20 mg/day atorvastatin and end of study (week 12 for QM and week 14 for Q2W subjects) the following drugs or supplements: red yeast rice, niacin (> 200 mg/day), > 1000 mg/day omega-3 fatty acids (eg, Docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA], prescription and non-prescription combined), and all other prescription lipid-regulating drugs (eg, fibrates and derivatives, ezetimibe, bile-acid sequestering resin, stanols, or probucol) except study-provided atorvastatin. 9) Subject has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to randomization, such as: anacetrapib, dalcetrapib or evacetrapib. 10) Treatment in the last 2 months prior to screening and lipid stabilization assessments with any of the following drugs: systemic cyclosporine, systemic steroids (eg, intravenous [IV], intramuscular [IM], or oral [PO] administration), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted). 11) Hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) below the lower limit of normal (LLN) or > 1.5 times the upper limit of normal (ULN), respectively, at screening. 12) Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) 2 times the ULN as determined by central laboratory analysis at screening or lipid stabilization assessments. 14) Creatine kinase (CK) > 3 times the ULN at screening or lipid stabilization assessments. 15) Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction (except diabetes). 16) Deep vein thrombosis or pulmonary embolism within 3 months prior to randomization. 17) Female subject who has either (1) not used (an) acceptable method(s) of birth control (see protocol) for at least 1 month prior to screening or (2) is not w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), in combination with oral (PO) atorvastatin daily (QD), compared with placebo Q2W and QM, in combination with PO atorvastatin QD, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in diabetic subjects with hyperlipidemia or mixed dyslipidemia.;Secondary Objective: •to evaluate the safety and tolerability of SC evolocumab Q2W and QM in combination with atorvastatin QD, compared with placebo Q2W and QM, in combination with atorvastatin QD, in diabetic subjects with hyperlipidemia or mixed dyslipidemia • to assess the effects of 12 weeks of SC evolocumab Q2W and QM in combination with atorvastatin QD, compared with placebo Q2W and QM, in combination with atorvastatin QD, on change from baseline in LDL-C, and percent change from baseline in non-HDL-C, ApoB100, total cholesterol, total cholesterol/HDL-C ratio, ApoB100/ApoA1 ratio, Lp(a), triglycerides, VLDL-C, and HDL-C in diabetic subjects with hyperlipidemia or mixed dyslipidemia • to assess the effects of 12 weeks of SC evolocumab Q2W and QM in combination with atorvastatin QD, compared with placebo Q2W and QM, in combination with atorvastatin QD, on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) in diabetic subjects with hyperlipidemia or mixed dyslipidemia;Primary end point(s): Co-Primary Efficacy Endpoints a) mean percent change from baseline in LDL-C at weeks 10 and 12 b) percent change from baseline in LDL-C at week 12;Timepoint(s) of evaluation of this end point: a) Weeks 10 and 12 b) Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Co-secondary efficacy endpoints are (1) the mean of weeks 10 and 12 and (2) 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 ApoB100 • percent change from baseline in the total cholesterol • percent change from baseline in the total cholesterol/HDL-C ratio • percent change from baseline in ApoB100/ApoA1 ratio • achievement of target LDL-C < 70 mg/dL (1.8 mmol/L) Tier 2 endpoints • 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: Weeks 10 and 12 | — |
Countries
Argentina, Brazil, Canada, China, Colombia, France, Korea, Republic of, Russian Federation, Turkey, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed