Study of Atorvastatin/Fenofibrate (LCP-AtorFen) Combination Therapy in Dyslipidemia

• Sponsor: Veloxis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00504829
• Collaborator: (none)
• Enrollment: 220
• Location: 1
• Arms: 3
• Duration (Months): 12
• Patients Per Site Per Month: 18.3

Study Details

Study Description

Brief Summary

The current study is designed to test the efficacy, safety and tolerability of LCP-AtorFen, a combination of atorvastatin and fenofibrate.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia	Drug: LCP-AtorFen; Drug: atorvastatin; Drug: fenofibrate	Phase 2

Detailed Description

This is a multicenter, randomized, double-blind, 12 week study with a 52-week open-label follow-up to evaluate the safety and efficacy of LCP-AtorFen (the combination of atorvastatin and fenofibrate) in the treatment of hyperlipidemia.

After a wash-out phase, eligible patients will be randomized on a 1:1:1 ratio to either LCP-AtorFen, atorvastatin or fenofibrate for 12 weeks. After the completion of the 12-week phase, all eligible patients will be offered to receive open-label LCP-AtorFen for another 52 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-Week, Multi-Center, Double-Blind, Randomized, Parallel-Group Study, Followed by a 12 Month Extension Study, of the Efficacy and Safety of LCP-AtorFen in Subjects With Dyslipidemia
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LCP-AtorFen LCP-AtorFen 40/100mg fixed-dose combination tablet of 40mg atorvastatin and 145mg fenofibrate for treatment of mixed dyslipidemia	Drug: LCP-AtorFen; 40mg atorvastatin combined with 100mg fenofibrate in a tablet for once daily treatment of dyslipidemia and mixed dyslipidemia
Active Comparator: atorvastatin atorvastatin 40mg tablet (Lipitor), as an adjunct to diet and exercise for treatment of mixed dyslipidemia	Drug: atorvastatin; dyslipidemia and mixed dyslipidemia; Other Names: Lipitor
Active Comparator: fenofibrate fenofibrate 145mg tablet (Tricor), as an adjunct to diet and exercise for treatment of mixed dyslipidemia	Drug: fenofibrate; dyslipidemia and mixed dyslipidemia; Other Names: Tricor

Outcome Measures

Primary Outcome Measures

1. Percent Changes From Baseline to End-of-treatment in Non-HDL Cholesterol, HDL Cholesterol, and Triglycerides by LCP-AtorFen Versus Atorvastatin Monotherapy [baseline(randomization) to 12 weeks]

   Mean percent change from baseline to end-of-treatment (12 weeks) for non-HDL cholesterol and triglycerides and the mean percent change from baseline to end-of-treatment for HDL cholesterol for AtorFen 40/100mg fixed-dose combination tablet versus atorvastatin 40mg tablet.

Secondary Outcome Measures

1. Percent Changes From Baseline to End-of-treatment in Non-HDL, HDL and LDL Cholesterol by LCP-AtorFen Versus Fenofibrate Monotherapy [baseline (week 0) to 12 weeks]

   Mean percent changes from baseline (Visit 3, Week 0) to end-of-treatment (Visit 6; Week 12) in non-HDL, HDL and LDL cholesterol by LCP-AtorFen versus fenofibrate monotherapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. A diagnosis of dyslipidemia (non-HDL-C >130 mg/dL and Triglycerides > or equal to 150 mg/dL and < or equal to 500 mg/dL).

2. Subject may be currently on a statin or other lipid-lowering therapy but must be willing and able to washout for 8 weeks if on a fibrate or high-dose niacin, 6 weeks if on a statin or low-dose niacin per day, or 4 weeks if on a bile acid sequestrant, ezetimibe, or >1000 mg of fish oil per day.

3. Other inclusion criteria might apply

Exclusion Criteria:

1. TGs > 500 mg/dL.

2. History of coronary heart disease (CHD), transient ischemic attacks, stroke or revascularization procedure in the six months prior.

3. Presence of an aortic aneurysm or resection of an aortic aneurysm within six months.

4. Poorly controlled diabetes mellitus (glycosylated hemoglobin >8.0% )or diabetes mellitus requiring insulin therapy.

5. Known lipoprotein lipase impairment or deficiency or Apo C-II deficiency or familial dysbetalipoproteinemia.

6. History of pancreatitis.

7. Known allergy or sensitivity to statins or fibrates.

8. Poorly controlled hypertension.

9. Other exclusion criteria might apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radiant Research, 515 N State Street, Suite 2700	Chicago	Illinois	United States	60610

Sponsors and Collaborators

• Veloxis Pharmaceuticals

Investigators

• Principal Investigator: Jeff Geohas, MD, Radiant Research
• Study Director: Dennis McCluskey, MD, Radiant Research
• Study Director: Harry Geisberg, MD, Radiant Research
• Study Director: Chivers Woodruff, Jr, MD, Radiant Research
• Study Director: Michael Noss, MD, Radiant Research
• Study Director: Michele Reynolds, MD, Radiant Research
• Study Director: James Zavoral, MD, Radiant Research
• Study Director: Randall Severance, MD, Radiant Research
• Study Director: Stephen Halpern, MD, Radiant Research
• Study Director: Linda Murray, MD, Radiant Research
• Study Director: Wayne Larson, MD, Radiant Research
• Study Director: Timothy Howards, MD, Medical Affiliated Research Center, Inc.
• Study Director: Cynthia Strout, MD, Coastal Carolina Research Center
• Study Director: Mark Kipnes, MD, Diabetes and Glandular Research Center, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Veloxis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00504829
• Other Study ID Numbers: LCP-AtorFen-2001
• First Posted: Jul 20, 2007
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Veloxis Pharmaceuticals: LCP-AtorFen; Non-HDL cholesterol; Triglycerides; HDL cholesterol; LDL cholesterol; Atorvastatin; Fenofibrate
• Additional relevant MeSH terms: Dyslipidemias; Atorvastatin; Fenofibrate

Study Results

Participant Flow

Recruitment Details	Subjects will be recruited from a combination of sources: advertising, clinical databases, clinical referrals, and the general subject population.
Pre-assignment Detail	The washout period for subjects on lipid-lowering therapy will be 4 to 8 weeks, depending on their regimen.

Arm/Group Title	LCP-AtorFen 40/100mg	Atorvastatin 40mg	Fenofibrate 145mg
Arm/Group Description	study drug arm Atorvastatin 40mg and fenofibrate 100mg	active control arm atorvastatin 40mg	active control arm fenofibrate 145mg
Period Title: Overall Study
STARTED	73	74	73
COMPLETED	67	70	63
NOT COMPLETED	6	4	10

Baseline Characteristics

Arm/Group Title	LCP-AtorFen 40/100mg	Atorvastatin 40mg	Fenofibrate 145mg	Total
Arm/Group Description	study drug arm Atorvastatin 40mg and fenofibrate 100mg	active control arm atorvastatin 40mg	active control arm fenofibrate 145mg	Total of all reporting groups
Overall Participants	73	74	73	220
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	73 100%	74 100%	73 100%	220 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.9 (10.74)	56.3 (9.88)	56.4 (10.58)	55.9 (10.38)
Sex: Female, Male (Count of Participants)
Female	33 45.2%	39 52.7%	33 45.2%	105 47.7%
Male	40 54.8%	35 47.3%	40 54.8%	115 52.3%
Region of Enrollment (participants) [Number]
United States	73 100%	74 100%	73 100%	220 100%

Outcome Measures

1. Primary Outcome

Title	Percent Changes From Baseline to End-of-treatment in Non-HDL Cholesterol, HDL Cholesterol, and Triglycerides by LCP-AtorFen Versus Atorvastatin Monotherapy
Description	Mean percent change from baseline to end-of-treatment (12 weeks) for non-HDL cholesterol and triglycerides and the mean percent change from baseline to end-of-treatment for HDL cholesterol for AtorFen 40/100mg fixed-dose combination tablet versus atorvastatin 40mg tablet.
Time Frame	baseline(randomization) to 12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population consisted of all subjects randomized who had at least one dose of study drug and one post-baseline (randomization) assessment

Arm/Group Title	LCP-AtorFen 40/100mg	Atorvastatin 40mg
Arm/Group Description	study drug arm Atorvastatin 40mg and fenofibrate 100mg	active control arm atorvastatin 40mg
Measure Participants	71	73
non-HDL	-44.8 (16.2)	-40.2 (17.3)
triglycerides	-49.1 (24.46)	-28.9 (32.25)
HDL	19.7 (21.38)	6.5 (18.77)

2. Secondary Outcome

Title	Percent Changes From Baseline to End-of-treatment in Non-HDL, HDL and LDL Cholesterol by LCP-AtorFen Versus Fenofibrate Monotherapy
Description	Mean percent changes from baseline (Visit 3, Week 0) to end-of-treatment (Visit 6; Week 12) in non-HDL, HDL and LDL cholesterol by LCP-AtorFen versus fenofibrate monotherapy
Time Frame	baseline (week 0) to 12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population consisted of all subjects randomized who had at least one dose of study drug and one post-baseline (randomization) assessment

Arm/Group Title	LCP-AtorFen 40/100mg	Fenofibrate 145mg
Arm/Group Description	study drug arm Atorvastatin 40mg and fenofibrate 100mg	active control arm fenofibrate 145mg
Measure Participants	71	73
non-HDL	-44.8 (16.2)	-16.1 (17.5)
LDL	-42.3 (20.01)	-13.9 (18.31)
HDL	19.7 (21.38)	18.2 (17.81)

Adverse Events

Adverse Event Reporting Description	For certain "Other (Not Including Serious) Adverse Events" some adverse events were monitored/assessed without regard to a specific adverse event term, and were therefore listed only by organ class.
Arm/Group Title	LCP-AtorFen 40/100mg		Atorvastatin 40mg		Fenofibrate 145mg
Arm/Group Description	study drug arm Atorvastatin 40mg and fenofibrate 100mg		active control arm atorvastatin 40mg		active control arm fenofibrate 145mg
All Cause Mortality
	LCP-AtorFen 40/100mg		Atorvastatin 40mg		Fenofibrate 145mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LCP-AtorFen 40/100mg		Atorvastatin 40mg		Fenofibrate 145mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/73 (1.4%)		0/74 (0%)		2/73 (2.7%)
Investigations
Alanine aminotransferase increased	1/73 (1.4%)		0/74 (0%)		0/73 (0%)
Hepatic enzyme increased	0/73 (0%)		0/74 (0%)		1/73 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	0/73 (0%)		0/74 (0%)		1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	LCP-AtorFen 40/100mg		Atorvastatin 40mg		Fenofibrate 145mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/73 (58.9%)		49/74 (66.2%)		48/73 (65.8%)
Endocrine disorders
Endocrine Disorders (any)	0/73 (0%)		2/74 (2.7%)		0/73 (0%)
Gastrointestinal disorders
Gastrointestinal Disorders (any)	13/73 (17.8%)		9/74 (12.2%)		10/73 (13.7%)
Abdominal distension	2/73 (2.7%)		2/74 (2.7%)		0/73 (0%)
Constipation	3/73 (4.1%)		0/74 (0%)		2/73 (2.7%)
Diarrhoea	0/73 (0%)		0/74 (0%)		2/73 (2.7%)
Dyspepsia	0/73 (0%)		1/74 (1.4%)		2/73 (2.7%)
Flatulence	3/73 (4.1%)		1/74 (1.4%)		3/73 (4.1%)
Gastro esophageal reflux diseases	1/73 (1.4%)		2/74 (2.7%)		0/73 (0%)
Nausea	1/73 (1.4%)		1/74 (1.4%)		2/73 (2.7%)
General disorders
General Disorders and Administration Site Conditions	5/73 (6.8%)		1/74 (1.4%)		5/73 (6.8%)
Fatigue	2/73 (2.7%)		0/74 (0%)		3/73 (4.1%)
Infections and infestations
Infections and Infestations (any)	10/73 (13.7%)		18/74 (24.3%)		13/73 (17.8%)
Bacteriuria	0/73 (0%)		0/74 (0%)		2/73 (2.7%)
Nasopharyngitis	4/73 (5.5%)		8/74 (10.8%)		2/73 (2.7%)
Sinusitis	0/73 (0%)		3/74 (4.1%)		1/73 (1.4%)
Upper respiratory tract infection	2/73 (2.7%)		3/74 (4.1%)		2/73 (2.7%)
Injury, poisoning and procedural complications
Injury, Poisoning and Procedural Complications (any)	3/73 (4.1%)		2/74 (2.7%)		3/73 (4.1%)
Foot fracture	0/73 (0%)		0/74 (0%)		2/73 (2.7%)
Investigations
Investigations (any)	13/73 (17.8%)		11/74 (14.9%)		13/73 (17.8%)
Alanine aminotransferase increased	3/73 (4.1%)		5/74 (6.8%)		2/73 (2.7%)
Aspartate aminotransferase increased	3/73 (4.1%)		1/74 (1.4%)		2/73 (2.7%)
Blood creatine phosphokinase increased	4/73 (5.5%)		2/74 (2.7%)		2/73 (2.7%)
Blood glucose increased	2/73 (2.7%)		1/74 (1.4%)		0/73 (0%)
Creatinine renal clearance decreased	2/73 (2.7%)		0/74 (0%)		5/73 (6.8%)
Gamma- glutamyltransferase increased	2/73 (2.7%)		0/74 (0%)		2/73 (2.7%)
Liver function test abnormal	2/73 (2.7%)		0/74 (0%)		1/73 (1.4%)
Metabolism and nutrition disorders
Metabolism and Nutrition (any)	1/73 (1.4%)		1/74 (1.4%)		3/73 (4.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and Connective Tissue Disorders (any)	8/73 (11%)		9/74 (12.2%)		9/73 (12.3%)
Arthralgia	1/73 (1.4%)		0/74 (0%)		2/73 (2.7%)
Back pain	1/73 (1.4%)		3/74 (4.1%)		1/73 (1.4%)
Musculoskeletal stiffness	0/73 (0%)		2/74 (2.7%)		0/73 (0%)
Myalgia	0/73 (0%)		2/74 (2.7%)		2/73 (2.7%)
Pain in extremity	1/73 (1.4%)		0/74 (0%)		2/73 (2.7%)
Tendonitis	2/73 (2.7%)		0/74 (0%)		0/73 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant and Unspecified (any)	0/73 (0%)		0/74 (0%)		2/73 (2.7%)
Nervous system disorders
Nervous System Disorders (any)	5/73 (6.8%)		5/74 (6.8%)		2/73 (2.7%)
Headache	1/73 (1.4%)		2/74 (2.7%)		0/73 (0%)
Psychiatric disorders
Psychiatric Disorders (any)	0/73 (0%)		1/74 (1.4%)		2/73 (2.7%)
Renal and urinary disorders
Renal and Urinary Disorders (any)	0/73 (0%)		2/74 (2.7%)		3/73 (4.1%)
Reproductive system and breast disorders
Reproductive System and Breast Disorders (any)	1/73 (1.4%)		1/74 (1.4%)		2/73 (2.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic and Mediastinal Disorders (any)	4/73 (5.5%)		7/74 (9.5%)		3/73 (4.1%)
Cough	0/73 (0%)		2/74 (2.7%)		0/73 (0%)
Nasal congestion	1/73 (1.4%)		2/74 (2.7%)		0/73 (0%)
Pharyngolaryngeal pain	2/73 (2.7%)		1/74 (1.4%)		0/73 (0%)
Pulmonary congestion	0/73 (0%)		2/74 (2.7%)		0/73 (0%)
Skin and subcutaneous tissue disorders
Skin and Subcutaneous Tissue Disorders (any)	0/73 (0%)		1/74 (1.4%)		4/73 (5.5%)
Pruritus	0/73 (0%)		0/74 (0%)		2/73 (2.7%)
Rash macular	0/73 (0%)		0/74 (0%)		2/73 (2.7%)
Vascular disorders
Vascular Disorders (any)	3/73 (4.1%)		2/74 (2.7%)		2/73 (2.7%)
Hypertension	1/73 (1.4%)		2/74 (2.7%)		0/73 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Individual investigators may publish data arising from their own subjects. The Principal Investigator will provide the Sponsor with copies of written publications (including abstracts and posters) at least 60 days in advance of submission.