ASA EFFECTS: Study to Evaluate the EFFECTS of Acetylsalicylic Acid (ASA) on Niaspan®-Induced Flushing in Subjects With Dyslipidemia

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00626392
• Collaborator: (none)
• Enrollment: 277
• Locations: 26
• Arms: 6
• Duration (Months): 2
• Patients Per Site: 10.7
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

The primary purpose of this study was to assess the effect of aspirin (ASA) on niacin extended-release (NER)-induced flushing in subjects with dyslipidemia.

Condition or Disease	Intervention/Treatment	Phase
Dyslipidemia	Drug: niacin extended-release (NER); Drug: aspirin (ASA); Drug: aspirin placebo (ASA Pbo)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 277 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-Blind, Parallel, Acetylsalicylic Acid (ASA) Run-In Study to Evaluate the EFFECTS of Acetylsalicylic Acid on Niaspan®-Induced Flushing in Subjects With Dyslipidemia
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NER 500; ASA run-in, ASA coadmin Aspirin (ASA) daily during run-in (1 week); ASA 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration period (4 weeks)	Drug: niacin extended-release (NER); Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period; Other Names: Niaspan ; Drug: aspirin (ASA); 325 mg tablets administered once daily; Other Names: acetylsalicylic acid
Experimental: NER 500; ASA Pbo run-in, ASA coadmin Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration period (4 weeks)	Drug: niacin extended-release (NER); Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period; Other Names: Niaspan ; Drug: aspirin (ASA); 325 mg tablets administered once daily; Other Names: acetylsalicylic acid ; Drug: aspirin placebo (ASA Pbo); Tablets administered once daily; Other Names: placebo
Experimental: NER 500; ASA Pbo run-in, ASA Pbo coadmin Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA Pbo 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration period (4 weeks)	Drug: niacin extended-release (NER); Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period; Other Names: Niaspan ; Drug: aspirin placebo (ASA Pbo); Tablets administered once daily; Other Names: placebo
Experimental: NER 1000; ASA run-in, ASA coadmin Aspirin (ASA) daily during run-in (1 week); ASA 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration period (4 weeks)	Drug: niacin extended-release (NER); Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period; Other Names: Niaspan ; Drug: aspirin (ASA); 325 mg tablets administered once daily; Other Names: acetylsalicylic acid
Experimental: NER 1000; ASA Pbo run-in, ASA coadmin Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration period (4 weeks)	Drug: niacin extended-release (NER); Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period; Other Names: Niaspan ; Drug: aspirin (ASA); 325 mg tablets administered once daily; Other Names: acetylsalicylic acid ; Drug: aspirin placebo (ASA Pbo); Tablets administered once daily; Other Names: placebo
Experimental: NER 1000; ASA Pbo run-in, ASA Pbo coadmin Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA Pbo 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration period (4 weeks)	Drug: niacin extended-release (NER); Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period; Other Names: Niaspan ; Drug: aspirin placebo (ASA Pbo); Tablets administered once daily; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment [From Baseline to end of Week 1]

   The maximum severity of flushing events subjects experienced during Week 1 of NER treatment was categorized as none, mild, moderate, severe, or very severe using the Flushing Assessment Tool via an e-diary. Flushing was assessed daily and the percentage of subjects with maximum flushing severity in each category was calculated.

Secondary Outcome Measures

1. Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment [4 weeks]

   The maximum severity of flushing events subjects experienced during 4 weeks of NER treatment was categorized as none, mild, moderate, severe, or very severe using the Flushing Assessment Tool via an e-diary. Flushing was assessed daily and the percentage of subjects with maximum flushing severity in each category was calculated.

2. Mean of Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment [4 weeks]

   Subjects assessed the severity of flushing events on a 10-point numeric rating scale of 1-3 (mild), 4-6 (moderate), 7-9 (severe), and 10 (very severe) using the Flushing Assessment Tool via an e-diary. For subjects who did not experience flushing, a score of 0 was assigned. Flushing was assessed daily.

3. Mean Number of Moderate or Greater Flushing Events Per Subject Per Week Overall During 4 Weeks of Niacin Extended-release (NER) Treatment [4 weeks]

   Flushing was assessed daily using the Flushing Assessment Tool via an e-diary and the mean number of flushing events per subject per week considered moderate or greater in severity was calculated. Flushing events were rated by the subject using a categorical scale of mild, moderate, severe, or very severe.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subject must be 18 years of age or older.

• If female, subject is either not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile, or is of childbearing potential and must agree to practice birth control for the duration of the study.

• Have dyslipidemia as demonstrated by laboratory results.

Exclusion Criteria:

• Have glycosylated hemoglobin (HbA1c) >/= 9.0%.

• Have nephrotic syndrome, dysproteinemias, or severe renal failure (glomerular filtration rate [GFR] < 30 mL/minute, as calculated from creatinine clearance).

• Have had unstable angina or an acute myocardial infarction (MI) within three months of the Screening Visit.

• Have had severe peripheral artery disease as evidenced by intermittent claudication within three months of the Screening Visit.

• Have had uncontrolled cardiac arrhythmias within three months of the Screening Visit.

• Have symptomatic heart failure defined as dyspnea at rest or with exertion (mild peripheral edema is not exclusionary).

• Have a systolic blood pressure measurement of > 180 mmHg or a diastolic blood pressure measurement of > 110 mmHg at the Screening or Baseline Visit.

• Have active gout or uric acid >/= 11 mg/dL.

• Have a history of hepatitis (acute or chronic), obstructive liver disease, or alanine aminotransferase (ALT; serum glutamic pyruvic transaminase [SGPT]) or aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase [SGOT]) values >/= 1.3 times the upper limit of normal (ULN) at the Screening Visit.

• Have creatine phosphokinase (CPK) >/= 3 x ULN at the Screening Visit.

• Have used an investigational study drug or participated in an investigational study within 30 days of the Screening Visit.

• Have a health condition or laboratory abnormality (inclusive of clinically significant laboratory results at Screening Visit), which, in the opinion of the Investigator, may be adversely affected by the procedures or study medications in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States	35801
2		Scottsdale	Arizona	United States	85251
3		Tucson	Arizona	United States	85710
4		Tucson	Arizona	United States	85712
5		Anaheim	California	United States	92801
6		Los Angeles	California	United States	90057
7		Newport Beach	California	United States	92660
8		Stockton	California	United States	95204
9		Vista	California	United States	90057
10		Westlake Village	California	United States	91361
11		Coral Gables	Florida	United States	33134
12		Jacksonville	Florida	United States	32259
13		Miami	Florida	United States	33186
14		Pembroke Pines	Florida	United States	33027
15		West Palm Beach	Florida	United States	33407
16		N. Dartmouth	Massachusetts	United States	02747
17		Rochester	New York	United States	14609
18		Charlotte	North Carolina	United States	28262
19		Winston-Salem	North Carolina	United States	27103
20		Penndel	Pennsylvania	United States	19047
21		Johnston	Rhode Island	United States	02919
22		Mt. Pleasant	South Carolina	United States	29464
23		Simpsonville	South Carolina	United States	29681
24		Colleyville	Texas	United States	76034
25		Houston	Texas	United States	77074
26		San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Abbott

Investigators

• Study Director: Roopal Thakkar, MD, Abbott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00626392
• Other Study ID Numbers: M10-241
• First Posted: Feb 29, 2008
• Last Update Posted: Sep 2, 2009
• Last Verified: Aug 1, 2009

• Additional relevant MeSH terms: Dyslipidemias; Flushing; Aspirin; Niacin

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 47 study sites in the United States between February and April, 2008.
Pre-assignment Detail	This study had a 1-week run-in (acetylsalicylic acid [ASA] 325 mg or ASA placebo [Pbo] once daily) prior to 4 weeks of niacin extended-release (NER) plus ASA/ASA Pbo coadministration. Ten of 277 randomized subjects discontinued before run-in due to withdrawal of consent (4), lost to follow-up (4), protocol violation (1), and other (1).

Arm/Group Title	NER 500; ASA run-in, ASA Coadmin	NER 500; ASA Pbo run-in, ASA Coadmin	NER 500; ASA Pbo run-in, ASA Pbo Coadmin	NER 1000; ASA run-in; ASA Coadmin	NER 1000; ASA Pbo run-in, ASA Coadmin	NER 1000; ASA Pbo run-in, ASA Pbo Coadmin
Arm/Group Description	Aspirin (ASA) 325 mg daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA Pbo 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration (4 weeks)	Aspirin (ASA) 325 mg daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA Pbo 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration (4 weeks)
Period Title: Run-in Period
STARTED	45	44	44	44	45	45
COMPLETED	44	43	41	43	41	44
NOT COMPLETED	1	1	3	1	4	1
Period Title: Run-in Period
STARTED	44	43	41	43	41	44
COMPLETED	40	38	31	36	36	38
NOT COMPLETED	4	5	10	7	5	6

Baseline Characteristics

Arm/Group Title	NER 500; ASA run-in, ASA Coadmin	NER 500; ASA Pbo run-in, ASA Coadmin	NER 500; ASA Pbo run-in, ASA Pbo Coadmin	NER 1000; ASA run-in, ASA Coadmin	NER 1000; ASA Pbo run-in, ASA Coadmin	NER 1000; ASA Pbo run-in, ASA Pbo Coadmin	Total
Arm/Group Description	Aspirin (ASA) 325 mg daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA Pbo 30 min prior to niacin extended-release ([NER], 500 mg starting dose), daily during coadministration (4 weeks)	Aspirin (ASA) 325 mg daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA 325 mg 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration (4 weeks)	Aspirin placebo (ASA Pbo) daily during run-in (1 week); ASA Pbo 30 min prior to niacin extended-release ([NER], 1000 mg starting dose), daily during coadministration (4 weeks)	Total of all reporting groups
Overall Participants	44	43	41	43	41	44	256
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.5 (10.62)	49.0 (10.48)	51.5 (12.58)	53.7 (12.4)	54.8 (11.08)	52.3 (12.45)	52.8 (11.73)
Sex: Female, Male (Count of Participants)
Female	21 47.7%	23 53.5%	21 51.2%	15 34.9%	21 51.2%	23 52.3%	124.0 48.4%
Male	23 52.3%	20 46.5%	20 48.8%	28 65.1%	20 48.8%	21 47.7%	132.0 51.6%
Region of Enrollment (participants) [Number]
United States	44 100%	43 100%	41 100%	43 100%	41 100%	44 100%	256.0 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment
Description	The maximum severity of flushing events subjects experienced during Week 1 of NER treatment was categorized as none, mild, moderate, severe, or very severe using the Flushing Assessment Tool via an e-diary. Flushing was assessed daily and the percentage of subjects with maximum flushing severity in each category was calculated.
Time Frame	From Baseline to end of Week 1

Outcome Measure Data

Analysis Population Description

All subjects in the modified intent-to-treat population, defined as all subjects who took at least 1 dose of study medication and who had at least 1 entry in the Flushing Assessment Tool e-diary (n = 251).

Arm/Group Title	Any Acetylsalicylic Acid	No Acetylsalicylic Acid
Arm/Group Description	Pooled arms that received acetylsalicylic acid (ASA) 325 mg during run-in and/or coadministration.	Pooled arms that received acetylsalicylic acid placebo (ASA Pbo) during run-in and coadministration.
Measure Participants	167	84
None	57	48
Mild	28	24
None/mild	85	71
Moderate	11	17
Severe	4	8
Very severe	1	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Any Acetylsalicylic Acid, No Acetylsalicylic Acid
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	No adjustments were made for multiple comparisons. P-values <= 0.05 were reported as statistically significant.
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment
Description	The maximum severity of flushing events subjects experienced during 4 weeks of NER treatment was categorized as none, mild, moderate, severe, or very severe using the Flushing Assessment Tool via an e-diary. Flushing was assessed daily and the percentage of subjects with maximum flushing severity in each category was calculated.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

All subjects in the modified intent-to-treat population, defined as all subjects who took at least 1 dose of study medication and who had at least 1 entry in the Flushing Assessment Tool e-diary (n = 251).

Arm/Group Title	Any Acetylsalicylic Acid	No Acetylsalicylic Acid
Arm/Group Description	Pooled arms that received acetylsalicylic acid (ASA) 325 mg during run-in and/or coadministration.	Pooled arms that received acetylsalicylic acid placebo (ASA Pbo) during run-in and coadministration.
Measure Participants	167	84
None	30	15
Mild	28	14
None/Mild	58	30
Moderate	28	35
Severe	11	23
Very severe	4	13

3. Secondary Outcome

Title	Mean of Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment
Description	Subjects assessed the severity of flushing events on a 10-point numeric rating scale of 1-3 (mild), 4-6 (moderate), 7-9 (severe), and 10 (very severe) using the Flushing Assessment Tool via an e-diary. For subjects who did not experience flushing, a score of 0 was assigned. Flushing was assessed daily.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

All subjects in the modified intent-to-treat population, defined as all subjects who took at least 1 dose of study medication and who had at least 1 entry in the Flushing Assessment Tool e-diary (n = 251).

Arm/Group Title	Any Acetylsalicylic Acid	No Acetylsalicylic Acid
Arm/Group Description	Pooled arms that received acetylsalicylic acid (ASA) 325 mg during run-in and/or coadministration.	Pooled arms that received acetylsalicylic acid placebo (ASA Pbo) during run-in and coadministration.
Measure Participants	167	84
Mean (Standard Deviation) [Scores on a Scale]	3.1 (2.86)	5.1 (3.16)

4. Secondary Outcome

Title	Mean Number of Moderate or Greater Flushing Events Per Subject Per Week Overall During 4 Weeks of Niacin Extended-release (NER) Treatment
Description	Flushing was assessed daily using the Flushing Assessment Tool via an e-diary and the mean number of flushing events per subject per week considered moderate or greater in severity was calculated. Flushing events were rated by the subject using a categorical scale of mild, moderate, severe, or very severe.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

All subjects in the modified intent-to-treat population, defined as all subjects who took at least 1 dose of study medication and who had at least 1 entry in the Flushing Assessment Tool e-diary (n = 251).

Arm/Group Title	Any Acetylsalicylic Acid	No Acetylsalicylic Acid
Arm/Group Description	Pooled arms that received acetylsalicylic acid (ASA) 325 mg during run-in and/or coadministration.	Pooled arms that received acetylsalicylic acid placebo (ASA Pbo) during run-in and coadministration.
Measure Participants	167	84
Mean (Standard Deviation) [Number of Events per Subject per Week]	0.3 (0.64)	0.8 (1.10)

Adverse Events

Arm/Group Title	Any Acetylsalicylic Acid		No Acetylsalicylic Acid
Arm/Group Description	Pooled arms that received acetylsalicylic acid (ASA) 325 mg during run-in and/or coadministration.		Pooled arms that received acetylsalicylic acid placebo (ASA Pbo) during run-in and coadministration.
All Cause Mortality
	Any Acetylsalicylic Acid		No Acetylsalicylic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Any Acetylsalicylic Acid		No Acetylsalicylic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/ (NaN)		1/ (NaN)
Gastrointestinal disorders
Esophageal ulcer	0/171 (0%)	0	1/85 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/171 (0.6%)	1	0/85 (0%)	0
Other (Not Including Serious) Adverse Events
	Any Acetylsalicylic Acid		No Acetylsalicylic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	119/ (NaN)		72/ (NaN)
Gastrointestinal disorders
Nausea	4/171 (2.3%)		1/85 (1.2%)
General disorders
Non-cardiac chest pain	1/171 (0.6%)		2/85 (2.4%)
Investigations
Blood creatine phosphokinase increased	0/171 (0%)		2/85 (2.4%)
Blood uric acid increased	0/171 (0%)		2/85 (2.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/171 (0.6%)		3/85 (3.5%)
Pain in extremity	0/171 (0%)		2/85 (2.4%)
Skin and subcutaneous tissue disorders
Rash	3/171 (1.8%)		2/85 (2.4%)
Vascular disorders
Flushing	117/171 (68.4%)		71/85 (83.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Provide Abbott at least sixty (60) days prior to submission for review, Abbott shall return comments within sixty (60) days of receipt of draft. Proposed draft shall be delayed an additional sixty (60) days in addition to the Review Period.