Primary Hyperlipidemia and Mixed Dyslipidemia Clinical Trial
— FLOREYOfficial title:
Double-blind, Randomized, Placebo-controlled, Single Site Study to Evaluate the Effects of Evolocumab (AMG 145) Treatment, Alone and in Combination With Atorvastatin, on Lipoprotein Kinetics
| Verified date | September 2018 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a randomized, double-blind, placebo-controlled trial to evaluate the effect of evolocumab, atorvastatin, and combination therapy on lipoprotein kinetics.
| Status | Completed |
| Enrollment | 89 |
| Est. completion date | March 5, 2015 |
| Est. primary completion date | February 13, 2015 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Male |
| Age group | 18 Years to 65 Years |
| Eligibility |
Inclusion Criteria: - Fasting LDL-C at screening = 100 mg/dL and = 190 mg/dL - Fasting triglycerides = 150 mg/dL - Body mass index (BMI) between 18.0 and 32.0 kg/m^2 - Framingham cardiac risk score 10% or less Exclusion Criteria: - Treatment with a lipid-regulating drug or over the counter supplement in the last 3 months prior to screening - History of coronary heart disease (CHD) or CHD equivalent - Uncontrolled hypertension - Diabetes mellitus |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Research Site | Adelaide | South Australia |
| Australia | Research Site | Nedlands | Western Australia |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
Australia,
Chan DC, Watts GF, Somaratne R, Wasserman SM, Scott R, Barrett PHR. Comparative Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition and Statins on Postprandial Triglyceride-Rich Lipoprotein Metabolism. Arterioscler Thromb Vasc Biol. 2018 Jul;38(7):1644-1655. doi: 10.1161/ATVBAHA.118.310882. Epub 2018 Jun 7. — View Citation
Watts GF, Chan DC, Dent R, Somaratne R, Wasserman SM, Scott R, Burrows S, R Barrett PH. Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism. Circulation. 2017 Jan 24;135(4):338-351. doi: 10.1161/CIRCULATIONAHA.116.025080. Epub 2016 Dec 9. — View Citation
Watts GF, Chan DC, Somaratne R, Wasserman SM, Scott R, Marcovina SM, Barrett PHR. Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics. Eur Heart J. 2018 Jul 14;39(27):2577-2585. doi: 10.1093/eurheartj/ehy122. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percent Change From Baseline in Low-density Lipoprotein (LDL) Apolipoprotein B-100 Fractional Catabolic Rate (FCR) | The fractional catabolic rate (the percentage of apolipoprotein B-100 in LDL which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation, and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism. | Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration. | |
| Secondary | Percent Change From Baseline in LDL-C at Day 50 | LDL-C was measured using ultrcentrifugation. | Baseline and Day 50 | |
| Secondary | Percent Change From Baseline in LDL Apolipoprotein B-100 Production Rate (PR) | The production rate of apolipoprotein B-100 in LDL was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate the production rate. | Baseline and Day 50 | |
| Secondary | Percent Change From Baseline in Lipoprotein (a) Fractional Catabolic Rate (FCR) | The fractional catabolic rate (the percentage of lipoprotein(a) (Lp[a]) which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. Lp(a) was isolated from plasma using an immunoprecipitation method employing immunomagnetic beads and polyacrylamide gel electrophoresis. Isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism. | Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration. | |
| Secondary | Percent Change From Baseline in Lipoprotein(a) Production Rate (PR) | The production rate of lipoprotein(a) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. Lp(a) was isolated from plasma using an immunoprecipitation method employing immunomagnetic beads and polyacrylamide gel electrophoresis. Isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism. | Baseline and Day 50 |