Study to Compare the Efficacy of Pitavastatin With That of Atorvastatin in Lowering Cholesterol Levels

Study of Pitavastatin 2 mg vs. Atorvastatin 10 mg and Pitavastatin 4 mg vs. Atorvastatin 20 mg (Following Up Titration) in Patients With Primary Hypercholesterolemia or Combined Dyslipidemia

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00249249

Enrollment

830

Registered

2005-11-07

Start date

2005-10-31

Completion date

2006-11-30

Last updated

2010-01-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dyslipidemia, Primary Hypercholesterolemia

Keywords

hypercholesterolemia, dyslipidemia, kowa, KRE, pitavastatin, NK-104

Brief summary

The purpose of this study is to compare the efficacy of pitavastatin with that of atorvastatin.

Detailed description

Following a wash-out dietary lead-in period, patients will receive either Atorvastatin or Pitavastatin during 12 weeks, in order to establish the efficacy of pitavastatin in reducing cholesterol levels.

Interventions

DRUGPitavastatin

DRUGAtorvastatin

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Males and females (age 18-75 years). * Non-pregnant, non-lactating females * Women of child bearing potential should use sustained contraceptive preparations or an approved mechanical contraceptive method. * Eligible and able to participate and have given informed consent * Must have been following a restrictive diet and does not eat or drink grapefruit * Diagnosis of primary hypercholesterolemia or combined dyslipidemia * Available for every clinic visit, which will occur in the morning.

Exclusion criteria

* Homozygous familial hypercholesterolemia or familial hypoalphalipoproteinemia * Conditions which may cause secondary dyslipidemia. * 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 by the investigator * Serum creatine kinase (CK) \>5 x upper limit of the reference range (ULRR). * Uncontrolled hypothyroidism * Severe acute illness or severe trauma in the last 3 months * Major surgery, 3 months prior to Visit 1 * Significant cardiovascular disease (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 (LV) ejection fraction \< 0.25 * History of symptomatic cerebrovascular disease * Conditions at the discretion of the investigator * Known HIV infection * Poorly controlled or uncontrolled hypertension. * 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 * Hypersensitivity reactions 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 * Regular clinic attendance in the morning impractical * Signs of mental dysfunction or other factors likely to limit ability to cooperate

Design outcomes

Primary

Measure	Time frame
Percent Change From Baseline Low Density Lipoprotein-cholesterol (LDL-C) at Week 12	Baseline to 12 weeks

Secondary

Measure	Time frame	Description
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)	Baseline to 12 weeks	percent change from baseline in high density lipoprotein-cholesterol (HDL-C)
TC:HDL-C Ratio	12 weeks	Ratio of mean total cholesterol to mean HDL-C at 12 weeks
Triglycerides (TG)	12 weeks	mean triglycerides at 12 weeks
Non-HDL:HDL Ratio	12 weeks	Ratio of non-HDL to HDL at 12 weeks
Apolipoprotein B (Apo B)	12 weeks	Apolipoprotein B at 12 weeks
Percent Change From Baseline in Total Cholesterol (TC)	Baseline to 12 Weeks	Percent change in total cholesterol from baseline to Week 12
Apo-B:Apo-A1 Ratio	12 weeks	Ratio of Apo-B to Apo-A1 at 12 weeks
High Sensitivity C-reactive Protein (Hs-CRP) at 12 Weeks	12 weeks	high sensitivity C-reactive protein (hs-CRP) at 12 weeks
Oxidized LDL at 12 Weeks	12 weeks	oxidized low density lipoprotein at 12 weeks
National Cholesterol Education Program [NCEP]LDL-C Target Attainment	up to 12 weeks	Number of patients achieving NCEP LDL-C target (LDL-C less than or equal to 130 mg/dL)
Apolipoprotein-A1 (Apo-A1)	12 weeks	Apolipoprotein-A1 at 12 weeks

Countries

Denmark, Finland, Germany, India, Israel, Italy, Netherlands, Norway, Poland, Russia, Spain, Sweden, United Kingdom

Participant flow

Recruitment details

First Patient In: 4 October 2005 Last Patient Out: 8 November 2006 A total of 39 investigators at 39 sites in India, Russia, Spain and Denmark received IRB approval to participate in this study and screened and randomized patients.

Pre-assignment details

Patients with major protocol violations were identified programmatically prior to unblinding to determine who should be excluded from the per protocol population.

Participants by arm

Arm	Count
Pitavastatin 2 mg QD Pitavastatin 2 mg daily	316
Atorvastatin 10 mg QD Atorvastatin 10 mg daily	102
Pitavastatin 4 mg QD Pitavastatin 4 mg daily	300
Atorvastatin 20 mg QD Atorvastatin 20 mg daily	103
Total	821

Baseline characteristics

Characteristic	Pitavastatin 2 mg QD	Atorvastatin 10 mg QD	Pitavastatin 4 mg QD	Atorvastatin 20 mg QD	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	97 Participants	27 Participants	93 Participants	30 Participants	247 Participants
Age, Categorical Between 18 and 65 years	219 Participants	75 Participants	207 Participants	73 Participants	574 Participants
Age Continuous	58.4 years STANDARD_DEVIATION 9.51	59.2 years STANDARD_DEVIATION 8.63	57.9 years STANDARD_DEVIATION 10.1	58.0 years STANDARD_DEVIATION 9.14	58.3 years STANDARD_DEVIATION 9.58
Sex: Female, Male Female	174 Participants	50 Participants	164 Participants	55 Participants	443 Participants
Sex: Female, Male Male	142 Participants	52 Participants	136 Participants	48 Participants	378 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	22 / 316	6 / 102	17 / 300	4 / 103
serious Total, serious adverse events	3 / 316	1 / 102	1 / 300	2 / 103