E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall aim is to clarify the postprandial dynamics of PCSK9 on the pathophysiology of
postprandial hypertriglyceridemia in people with type 2 diabetes. The effect of 12 weeks
treatment with Evolocumab 140 mg s.c. Q2W on postprandial lipid and lipoprotein
metabolism will be assessed in patients with type 2 diabetes (n=12) in an one-arm unblinded
clinical trial. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female (non-fertile or using a medically approved birth control method)
overweight/obese subjects with T2D treated with lifestyle counselling and a stable
metformin dose for at least three months
- age 18–77 yrs.
- BMI 25–40 kg/m2
- triglycerides between 1.5–4.5 mmol/L and LDL cholesterol >1.8 but ≤4.0 mmol/L (on
Atorvastatin 20 mg/day)
- HbA1c: ≤9%. |
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E.4 | Principal exclusion criteria |
- Type 1 diabetes
- apoE2/2 phenotype
- ALT/AST > 3×ULN
- CK>3×UNL
- GFR <60 ml/min
- clinically significant TSH outside the normal range
- BMI >40 kg/m2
- HbA1C > 9.0 %
- fasting TG > 4.5 mmol/l
- total chol > 7.0 mmol/l
- positive urine or serum pregnancy test
- untreated or inadequately treated hypertension defined as blood pressure >160 mmHg
systolic and/or >105 mmHg diastolic, use of thiazide diuretics at a dose of ≥25 mg/day
- subject not on a stable dose of atorvastatin (20 mg/ day before randomization)
- lipid-lowering drugs other than statins within 3 months
- any other diabetes medication except diet + metformin
- history/diagnosis of diabetes nephropathy / retinopathy
- smoking
- weekly alcohol use over 24 doses for men and 16 for women
- history of MI, ACS or coronary revascularization (PCI or CABG) within the last 6 mos.
- NYHA class III/IV congestive heart failure persisting despite treatment
- history of hemorrhagic stroke
- hypersensitivity to any of the excipients found in the drug product
- use of estrogen therapy
- current use of antithrombotic or anticoagulant therapy
- known bleeding tendency that would be an contraindication to heparin test
- history of cancer within the past 5 years (except for adequately treated basal cell skin
cancer, squamous cell skin cancer or in situ cervical cancer)
- women of childbearing potential not protected by effective birth control method and/or
not willing to be tested for pregnancy
- patient considered by the investigator or any sub-investigator as inappropriate for this
study for any reason |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
a. Chylomicron (Sf 400) TG IAUC and apoB48 IAUC during the standardized fat-rich mixed
meal test
b. VLDL1, VLDL2 and LDL production and fractional catabolic rates
c. Visceral fat volume and liver fat content (%) determined by MRI |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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the last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |