Hypercholesterolemia or Combined Dyslipidemia
Conditions
Keywords
Kowa, Hypercholesterolemia, combined, dyslipidemia, elderly, pitavastatin, NK-104
Brief summary
The purpose of this study is to compare the efficacy and safety of pitavastatin with that of pravastatin in elderly patients
Detailed description
Following a wash-out dietary lead-in period, patients will receive either Preavastatin or Pitavastatin during 12 weeks, in order to establish the efficacy of pitavastatin in reducing cholesterol levels.
Interventions
DRUGPitavastatin
DRUGPravastatin
Sponsors
Kowa Research Europe
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and postmenopausal females (aged 65 years and older * Eligible, able to participate, have given informed consent * Must have been following a restrictive diet * Diagnosis of primary hypercholesterolemia or combined dyslipidemia * Serum CK must be less than or equal to 1.5 x ULRR at 2 of 3 permitted evaluations between Week -4 and -1 * Agree to be available
Exclusion criteria
* Homozygous familial hypercholesterolemia * Conditions which may cause secondary dyslipidemia * Uncontrolled diabetes mellitus (HbA1c \>8%). * Any condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug. * History of pancreatic injury or pancreatitis, or impaired pancreatic function/injury * Liver injury * Impaired renal function * Current obstruction of the urinary tract or difficulty in voiding due to mechanical as well as inflammatory conditions, which is likely to require intervention during the course of the study or is regarded as clinically meaningful * Serum CK \>5 x ULRR without clinical explanation * Uncontrolled hypothyroidism defined as TSH \>ULRR * Any severe acute illness or severe trauma in the last 3 months prior to Visit 1 * Major surgery, 3 months prior to Visit 1 * Significant CVD prior to randomization * Evidence of symptomatic heart failure, gross cardiac enlargement; significant heart block or cardiac arrhythmias. History of uncontrolled complex ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardias with a ventricular response rate of \> 100 beats per minute at rest. * Left ventricular ejection fraction \<0.25; * History of symptomatic cerebrovascular disease * Any other conditions at the discretion of the investigator * Known HIV infection * Poorly controlled or uncontrolled hypertension * Prior or current known muscular or neuromuscular disease of any type; * Neoplastic disease * Drug abuse or continuous consumption of more than 65 mL pure alcohol per day * Exposure to any investigational new drug within 30 days of study entry or ingestion of any drug known to be toxic to a major organ system * Current or recent use of supplements known to alter lipid metabolism * History of hypersensitivity to other HMG-CoA reductase inhibitors; * Concomitant medication not permitted * Resistant to lipid-lowering medications. Known hypersensitivity or intolerance to any lipid lowering agent * Excessive obesity * Any factor which makes regular clinic attendance in the morning impractical ---Signs of mental dysfunction or other factors likely to limit ability to cooperate with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LDL-C | Baseline to 12 weeks | Percent change from baseline in low density cholesterol (LDL-C) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in TC | Baseline to 12 weeks | Percent change from baseline in total cholesterol (TC) |
Countries
Denmark, Germany, Israel, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pitavastatin 1 mg Pitavastatin 1 mg once daily | 207 |
| Pravastatin 10 mg Pravastatin 10 mg once daily | 103 |
| Pitavastatin 2 mg Pitavastatin 2 mg once daily | 224 |
| Pravastatin 20 mg Pravastatin 20 mg once daily | 96 |
| Pitavastatin 4 mg Pitavastatin 4 mg once daily | 210 |
| Pravastatin 40 mg Pravastatin 40 mg once daily | 102 |
| Total | 942 |
Baseline characteristics
| Characteristic | Pravastatin 10 mg | Pitavastatin 2 mg | Pravastatin 20 mg | Pitavastatin 4 mg | Pravastatin 40 mg | Pitavastatin 1 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 103 Participants | 224 Participants | 96 Participants | 210 Participants | 102 Participants | 207 Participants | 942 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 70.5 years STANDARD_DEVIATION 4.61 | 70.5 years STANDARD_DEVIATION 4.49 | 69.9 years STANDARD_DEVIATION 4.51 | 70.2 years STANDARD_DEVIATION 4.1 | 70.2 years STANDARD_DEVIATION 4.94 | 70.0 years STANDARD_DEVIATION 4.6 | 70.2 years STANDARD_DEVIATION 4.49 |
| Sex: Female, Male Female | 54 Participants | 124 Participants | 48 Participants | 121 Participants | 42 Participants | 118 Participants | 507 Participants |
| Sex: Female, Male Male | 49 Participants | 100 Participants | 48 Participants | 89 Participants | 60 Participants | 89 Participants | 435 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 59 / — | 36 / — | 62 / — | 24 / — | 52 / — | 23 / — |
| serious Total, serious adverse events | 1 / — | 0 / — | 2 / — | 1 / — | 3 / — | 3 / — |
Outcome results
Primary
Percent Change From Baseline in LDL-C
Percent change from baseline in low density cholesterol (LDL-C)
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin 1 mg | Percent Change From Baseline in LDL-C | -31.43 Percent change | Standard Deviation 11.833 |
| Pravastatin 10 mg | Percent Change From Baseline in LDL-C | -22.41 Percent change | Standard Deviation 14.051 |
| Pitavastatin 2 mg | Percent Change From Baseline in LDL-C | -38.99 Percent change | Standard Deviation 13.069 |
| Pravastatin 20 mg | Percent Change From Baseline in LDL-C | -28.83 Percent change | Standard Deviation 11.054 |
| Pitavastatin 4 mg | Percent Change From Baseline in LDL-C | -44.31 Percent change | Standard Deviation 13.695 |
| Pravastatin 40 mg | Percent Change From Baseline in LDL-C | -33.98 Percent change | Standard Deviation 14.299 |
Secondary
Percent Change From Baseline in TC
Percent change from baseline in total cholesterol (TC)
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pitavastatin 1 mg | Percent Change From Baseline in TC | -22.19 Percent change | Standard Deviation 8.899 |
| Pravastatin 10 mg | Percent Change From Baseline in TC | -15.34 Percent change | Standard Deviation 11.037 |
| Pitavastatin 2 mg | Percent Change From Baseline in TC | -26.68 Percent change | Standard Deviation 9.429 |
| Pravastatin 20 mg | Percent Change From Baseline in TC | -20.61 Percent change | Standard Deviation 8.426 |
| Pitavastatin 4 mg | Percent Change From Baseline in TC | -30.75 Percent change | Standard Deviation 10.461 |
| Pravastatin 40 mg | Percent Change From Baseline in TC | -24.07 Percent change | Standard Deviation 10.907 |