Dysbetalipoproteinemia (Fredrickson Type III Hyperlipoproteinemia)
Conditions
Interventions
Trade Name: Crestor
Product Name: Crestor
Product Code: AZD4522
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rosuvastatin
Current Sponsor code: AZD4522
Concentration unit: mg milligram
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the randomized crossover period of the study subjects must fulfill all of the following criteria. 1. Fasting TC concentrations > 200 mg/dL (5.2 mmol/L) at Visits 2 and 3 (or Visits 3 and 3.1 if Visit 3.1 is performed). 2. Fasting TG > 200 mg/dL (2.3 mmol/L) at Visits 2 and 3 (or Visits 3 and 3.1 if Visit 3.1 is performed). 3. Diagnosis of dysbetalipoproteinemia (Fredrickson Type III hyperlipoproteinemia) defined as: - VLDL-C/VLDL-TG mass ratio >0.35 at Visit 2, or - The concurrence of mixed hyperlipidemia (fasting TC > 200 mg/dL, fasting TG > 200 mg/dL at Visits 2 and 3 (or Visits 3 and 3.1 if Visit 3.1 is performed)) and a genotype of ApoE published to be associated with dysbetalipoproteinemia. 4. Male and female subjects aged 18 years and older. 5. Written informed consent to participate in the study. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. Use of cholesterol-lowering drugs, lipid lowering dietary supplements or food additives, including margarine containing plant sterols, eg, Benecol®, after Visit 1 (Week –6), except in accordance with the protocol as co-administered therapy (ie, a fenofibrate) with rosuvastatin 40 mg at Weeks 30 to 36. Subjects who have previously taken probucol should have discontinued its use 12 months before inclusion into this study. 2. History of statin induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins), including rosuvastatin. 3. Pregnant women, women who are breast-feeding, and women of childbearing potential who are not using chemical or mechanical contraception, or have a positive serum pregnancy test (a serum b-human chorionic gonadotrophin [b-HCG] analysis). 4. Fasting serum glucose of >180 mg/dL (9.99 mmol/L) or HbA1c >9% at Visit 1 (Week –6) or subjects with a history of diabetic ketoacidosis within the past 5 years. 5. Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH) >1.5 times the upper limit of normal (ULN) at Visit 1 (Week –6) or subjects whose thyroid replacement therapy was initiated or modified within the last 3 months. 6. Use of specified concomitant medications, as detailed in Appendix E. 8. Current active liver disease or hepatic dysfunction (excluding a confirmed diagnosis of Gilbert’s disease) as defined by elevations of ³2 times the ULN in any of the following liver function tests: ALT, AST or bilirubin prior to the initiation of rosuvastatin therapy. 9. Serum CK ³ 3 times ULN (unless explained by exercise) anytime during dietary period. 10. Serum creatinine >2.0 mg/dL (176 mmol/L) before the treatment phase, 4+ proteinuria on urine dipstick, or a history of renal transplantation before the treatment period. 12. Participation in another investigational drug study 95 mmHg or resting systolic blood pressure of > 200 mmHg recorded at any visit during the dietary period (taken from the mean of 3 readings). 17. Fasting triglyceride >1000 mg/dL (11.4 mmol/L) at any time during the dietary lead in or a history of pancreatitis while on treatment for dysbetalipoproteinemia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Percentage change from baseline in non-HDL-C with rosuvastatin 10 mg, rosuvastatin 20 mg, and pravastatin 40 mg after 6 weeks of treatment at a given dose during the 18-week randomized crossover period. ;Main Objective: The primary objective of this study is to evaluate the efficacy of once daily treatment with rosuvastatin 10 mg, rosuvastatin 20 mg, and pravastatin 40 mg in subjects with dysbetalipoproteinemia by assessment of the percentage change from baseline in non-HDL-C after 6 weeks of treatment at a given dose during the 18-week randomized crossover period. ;Secondary Objective: The secondary objectives for the randomized crossover period are to evaluate the efficacy of once daily treatment with rosuvastatin 10 mg, rosuvastatin 20 mg, and pravastatin 40 mg in subjects with dysbetalipoproteinemia after 6 weeks of treatment at a given dose during the 18-week randomized crossover period by assessment of: 1. The percentage of subjects who achieve their NCEP ATP III non-HDL-C goal. 2. The percentage of subjects who achieve their NCEP ATP III LDL-C goal. 3. The percentage of subjects who achieve their NCEP ATP III optimal TG level. 4. The percentage of subjects who achieve both their NCEP ATP III non-HDL-C goal and their NCEP ATP III optimal TG level. 5. The percentage change from baseline in combined IDL-C and VLDL-C as measured by ultracentrifugation. 6. The percentage change from baseline in e.g. IDL-C, VLDL-C, LDL-C, TC, HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C, RLP-C, TG, IDL-TG. | — |
Countries
Norway
Outcome results
None listed