Study to Compare the Efficacy and Safety of Pitavastatin and Pravastatin in Elderly Patients

• Sponsor: Kowa Research Europe (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00257686
• Collaborator: (none)
• Enrollment: 962
• Locations: 62
• Arms: 6
• Duration (Months): 8
• Patients Per Site: 15.5
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of pitavastatin with that of pravastatin in elderly patients

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia or Combined Dyslipidemia	Drug: Pitavastatin; Drug: Pravastatin	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 962 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study Of Pitavastatin 1 Mg Vs. Pravastatin 10 Mg, Pitavastatin 2 Mg Vs. Pravastatin 20 Mg And Pitavastatin 4 Mg Vs. Pravastatin 40 Mg (Following Up-Titration) In Elderly Patients With Primary Hypercholesterolemia Or Combined Dyslipidemia
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: May 1, 2006
• Actual Study Completion Date: May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pitavastatin 1 mg Pitavastatin 1 mg once daily	Drug: Pitavastatin
Active Comparator: Pravastatin 10 mg Pravastatin 10 mg once daily	Drug: Pravastatin
Experimental: Pitavastatin 2 mg Pitavastatin 2 mg once daily	Drug: Pitavastatin
Active Comparator: Pravastatin 20 mg Pravastatin 20 mg once daily	Drug: Pravastatin
Experimental: Pitavastatin 4 mg Pitavastatin 4 mg once daily	Drug: Pitavastatin
Active Comparator: Pravastatin 40 mg Pravastatin 40 mg once daily	Drug: Pravastatin

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in LDL-C [Baseline to 12 weeks]

   Percent change from baseline in low density cholesterol (LDL-C)

Secondary Outcome Measures

1. Percent Change From Baseline in TC [Baseline to 12 weeks]

   Percent change from baseline in total cholesterol (TC)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCBR A/S	Aalborg		Denmark
2	Copenhagen University Hospital	Copenhagen		Denmark
3	Medical Center	Copenhagen		Denmark
4	CCBR A/S	Vejle		Denmark
5	Kardiologische Gemeinschaftspraxis Prof. Reifart	Bad Soden / Taunus		Germany
6	Praxis Dr. Boenninghoff	Beckum		Germany
7	Klinische Forschung Berlin Mitte	Berlin		Germany
8	GWT-TUK mbH, Zentrum fur Klinische Studien	Dresden		Germany
9	Gemeinschaftspraxis Dr. Krause, Th. Menke	Goch		Germany
10	Klinische Forschung Hamburg	Hamburg		Germany
11	Innere Medizin I / Medizinische Klinik	Heidelberg		Germany
12	Gemeinschaftspraxis H. Holz Dr. med, K. W. Klingl	Lampertheim		Germany
13	ZET-Studien GmbH Leipzing	Leipzig		Germany
14	Internistische Gemeinschaftspraxis	Mainz		Germany
15	Praxis Dr. Wachter	Mannheim		Germany
16	Gemeinschaftspraxis Melcherstaette	Melcherstaette		Germany
17	Gemeinschaftspraxis Dr. Senftleber, Dr. Kohler	Messkirch		Germany
18	Praxisgemeinschaft im Kleinen Biergrund	Offenbach/M		Germany
19	Gemeinschaftspraxis Melcherstaette	Stuhr-Brinkum		Germany
20	Gemeinschaftspraxis Drs. Mockesch	Weinheim		Germany
21	Intermed Institud Fur Klinische Forschung und Arzn	Wiesbaden		Germany
22	Gemeinschaftspraxis Dr. Emden, Frank Drewes	Worpswede		Germany
23	Department of Internal Medicine, Soroka Medical Center	Beersheva		Israel
24	Department of Internal Medicine A, Rambal Medical Center	Haifa		Israel
25	Department of Internal Medicine, Wolfson Medical Center	Holon		Israel
26	Center for Research, Hadassah University Hospital	Jerusalem Ein Kerem		Israel
27	Meir Hospital	Kfar Saba		Israel
28	Department of Medicine, Hadassah Medical Center	Mount Scopus Jerusalem		Israel
29	Department of Internal Medicine, Rivka Sieff Medical Center	Safed		Israel
30	Institute of Metabolic Diseases	Tel Aviv		Israel
31	Institue of Lipid & Atherosclerosis Research	Tel Hashomer		Israel
32	Andromed Oost	ES Velp		Netherlands
33	Andromed Noord	Groningen		Netherlands
34	Vasculair Onderzoek Centrum Hoorn	Hoorn		Netherlands
35	Andromed Leiden	Leiden		Netherlands
36	Andromed Nijmegen	Rotterdam		Netherlands
37	Andromed Rotterdam	Rotterdam		Netherlands
38	Albert Schweitzer ziekenhuis	Sliedrecht		Netherlands
39	Andromed Breda	VL Breda		Netherlands
40	Rivierenland Tiel	WP Tiel		Netherlands
41	Andromed Zoetermeer	Zoetermeer		Netherlands
42	Albert Schweitzer ziekenhuis	Zwijndrecht		Netherlands
43	Oldfield Surgery	Bath		United Kingdom
44	St James's Surgery	Bath		United Kingdom
45	The Pulteney Practice	Bath		United Kingdom
46	Birmingham Clinical Research Centre	Birmingham		United Kingdom
47	Stonehill Medical Center	Bolton		United Kingdom
48	Chorley Clinical Research Centre	Chorley		United Kingdom
49	Saltash Health Center	Cornwall		United Kingdom
50	Gomersal Lane Surgery	Dronfield		United Kingdom
51	Townhead Research	Irvine		United Kingdom
52	Crosby Clinical Research Centre	Liverpool		United Kingdom
53	The Symons Medical Center	Maidenhead		United Kingdom
54	Manchester Clinical Research Centre	Manchester		United Kingdom
55	Greenwood Medical Center	Nottingham		United Kingdom
56	Reading Clinical Research Centre	Reading		United Kingdom
57	Elm Lane Surgery	Sheffield		United Kingdom
58	Brook Lane Surgery	Southampton		United Kingdom
59	Bradford Road Medical Center	Wiltshire		United Kingdom
60	Rowden Medical Partnership	Wiltshire		United Kingdom
61	The Porch Surgery	Wiltshire		United Kingdom
62	The Burns Medical Practice	Yorkshire		United Kingdom

Sponsors and Collaborators

• Kowa Research Europe

Investigators

• Study Director: Dragos Budinski, MD, Medical Director

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00257686
• Other Study ID Numbers: NK-104-306
• First Posted: Nov 23, 2005
• Last Update Posted: Mar 16, 2010
• Last Verified: Mar 1, 2010

• Keywords provided by , ,: Kowa; Hypercholesterolemia; combined; dyslipidemia; elderly; pitavastatin; NK-104
• Additional relevant MeSH terms: Hypercholesterolemia; Dyslipidemias; Pravastatin; Pitavastatin

Study Results

Participant Flow

Arm/Group Title	Pitavastatin 1 mg	Pravastatin 10 mg	Pitavastatin 2 mg	Pravastatin 20 mg	Pitavastatin 4 mg	Pravastatin 40 mg
Arm/Group Description	Pitavastatin 1 mg once daily	Pravastatin 10 mg once daily	Pitavastatin 2 mg once daily	Pravastatin 20 mg once daily	Pitavastatin 4 mg once daily	Pravastatin 40 mg once daily
Period Title: Overall Study
STARTED	209	108	226	99	216	104
Safety Population	207	103	224	96	210	102
COMPLETED	188	89	208	88	194	95
NOT COMPLETED	21	19	18	11	22	9

Baseline Characteristics

Arm/Group Title	Pitavastatin 1 mg	Pravastatin 10 mg	Pitavastatin 2 mg	Pravastatin 20 mg	Pitavastatin 4 mg	Pravastatin 40 mg	Total
Arm/Group Description	Pitavastatin 1 mg once daily	Pravastatin 10 mg once daily	Pitavastatin 2 mg once daily	Pravastatin 20 mg once daily	Pitavastatin 4 mg once daily	Pravastatin 40 mg once daily	Total of all reporting groups
Overall Participants	207	103	224	96	210	102	942
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	207 100%	103 100%	224 100%	96 100%	210 100%	102 100%	942 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.0 (4.60)	70.5 (4.61)	70.5 (4.49)	69.9 (4.51)	70.2 (4.10)	70.2 (4.94)	70.2 (4.49)
Sex: Female, Male (Count of Participants)
Female	118 57%	54 52.4%	124 55.4%	48 50%	121 57.6%	42 41.2%	507 53.8%
Male	89 43%	49 47.6%	100 44.6%	48 50%	89 42.4%	60 58.8%	435 46.2%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in LDL-C
Description	Percent change from baseline in low density cholesterol (LDL-C)
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pitavastatin 1 mg	Pravastatin 10 mg	Pitavastatin 2 mg	Pravastatin 20 mg	Pitavastatin 4 mg	Pravastatin 40 mg
Arm/Group Description	Pitavastatin 1 mg once daily	Pravastatin 10 mg once daily	Pitavastatin 2 mg once daily	Pravastatin 20 mg once daily	Pitavastatin 4 mg once daily	Pravastatin 40 mg once daily
Measure Participants	207	103	224	96	210	102
Mean (Standard Deviation) [Percent change]	-31.43 (11.833)	-22.41 (14.051)	-38.99 (13.069)	-28.83 (11.054)	-44.31 (13.695)	-33.98 (14.299)

2. Secondary Outcome

Title	Percent Change From Baseline in TC
Description	Percent change from baseline in total cholesterol (TC)
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pitavastatin 1 mg	Pravastatin 10 mg	Pitavastatin 2 mg	Pravastatin 20 mg	Pitavastatin 4 mg	Pravastatin 40 mg
Arm/Group Description	Pitavastatin 1 mg once daily	Pravastatin 10 mg once daily	Pitavastatin 2 mg once daily	Pravastatin 20 mg once daily	Pitavastatin 4 mg once daily	Pravastatin 40 mg once daily
Measure Participants	207	103	224	96	210	102
Mean (Standard Deviation) [Percent change]	-22.19 (8.899)	-15.34 (11.037)	-26.68 (9.429)	-20.61 (8.426)	-30.75 (10.461)	-24.07 (10.907)

Adverse Events

Arm/Group Title	Pitavastatin 1 mg		Pravastatin 10 mg		Pitavastatin 2 mg		Pravastatin 20 mg		Pitavastatin 4 mg		Pravastatin 40 mg
Arm/Group Description	Pitavastatin 1 mg once daily		Pravastatin 10 mg once daily		Pitavastatin 2 mg once daily		Pravastatin 20 mg once daily		Pitavastatin 4 mg once daily		Pravastatin 40 mg once daily
All Cause Mortality
	Pitavastatin 1 mg		Pravastatin 10 mg		Pitavastatin 2 mg		Pravastatin 20 mg		Pitavastatin 4 mg		Pravastatin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Pitavastatin 1 mg		Pravastatin 10 mg		Pitavastatin 2 mg		Pravastatin 20 mg		Pitavastatin 4 mg		Pravastatin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		0/ (NaN)		2/ (NaN)		1/ (NaN)		3/ (NaN)		3/ (NaN)
Cardiac disorders
Acute myocardial infarction	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		0/210 (0%)		1/102 (1%)
Myocardial infarction	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		1/210 (0.5%)		0/102 (0%)
Hepatobiliary disorders
Cholecystitis	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		0/210 (0%)		1/102 (1%)
Cholelithiasis	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		0/210 (0%)		1/102 (1%)
Injury, poisoning and procedural complications
Concussion	0/207 (0%)		0/103 (0%)		1/224 (0.4%)		0/96 (0%)		0/210 (0%)		0/102 (0%)
Femoral neck fracture	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		1/210 (0.5%)		0/102 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		1/210 (0.5%)		0/102 (0%)
Spinal column stenosis	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		1/210 (0.5%)		0/102 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	0/207 (0%)		0/103 (0%)		0/224 (0%)		1/96 (1%)		0/210 (0%)		0/102 (0%)
Nervous system disorders
Cerebral thrombosis	1/207 (0.5%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		0/210 (0%)		0/102 (0%)
Renal and urinary disorders
Urinary incontinence	0/207 (0%)		0/103 (0%)		1/224 (0.4%)		0/96 (0%)		0/210 (0%)		0/102 (0%)
Vascular disorders
Bleeding varicose vein	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		0/210 (0%)		1/102 (1%)
Hypertensive crisis	0/207 (0%)		0/103 (0%)		0/224 (0%)		0/96 (0%)		0/210 (0%)		1/102 (1%)
Other (Not Including Serious) Adverse Events
	Pitavastatin 1 mg		Pravastatin 10 mg		Pitavastatin 2 mg		Pravastatin 20 mg		Pitavastatin 4 mg		Pravastatin 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/ (NaN)		36/ (NaN)		62/ (NaN)		24/ (NaN)		52/ (NaN)		23/ (NaN)
Gastrointestinal disorders
Constipation	10/207 (4.8%)		5/103 (4.9%)		6/224 (2.7%)		4/96 (4.2%)		9/210 (4.3%)		3/102 (2.9%)
Nausea	5/207 (2.4%)		5/103 (4.9%)		6/224 (2.7%)		1/96 (1%)		3/210 (1.4%)		0/102 (0%)
General disorders
Fatigue	2/207 (1%)		4/103 (3.9%)		0/224 (0%)		0/96 (0%)		4/210 (1.9%)		0/102 (0%)
Infections and infestations
Nasopharyngitis	15/207 (7.2%)		6/103 (5.8%)		16/224 (7.1%)		5/96 (5.2%)		19/210 (9%)		7/102 (6.9%)
Influenza	7/207 (3.4%)		6/103 (5.8%)		16/224 (7.1%)		6/96 (6.3%)		19/210 (9%)		7/102 (6.9%)
Upper respiratory infection	3/207 (1.4%)		4/103 (3.9%)		2/224 (0.9%)		1/96 (1%)		3/210 (1.4%)		3/102 (2.9%)
Musculoskeletal and connective tissue disorders
Myalgia	3/207 (1.4%)		3/103 (2.9%)		11/224 (4.9%)		2/96 (2.1%)		4/210 (1.9%)		2/102 (2%)
Back pain	6/207 (2.9%)		3/103 (2.9%)		9/224 (4%)		1/96 (1%)		3/210 (1.4%)		2/102 (2%)
Nervous system disorders
Headache	8/207 (3.9%)		3/103 (2.9%)		9/224 (4%)		4/96 (4.2%)		4/210 (1.9%)		2/102 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.