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

Study Overview
=================
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.

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

Conditions
-----------------
Dyslipidemia

Intervention / Treatment
-----------------
* Drug: niacin extended-release (NER)
* Drug: aspirin (ASA)
* Drug: aspirin placebo (ASA Pbo)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NER 500; ASA run-in, ASA coadmin<br>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)<br>* Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period<br>* Other names: Niaspan;Drug: aspirin (ASA)<br>* 325 mg tablets administered once daily<br>* Other names: acetylsalicylic acid;|
| Experimental: NER 500; ASA Pbo run-in, ASA coadmin<br>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)<br>* Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period<br>* Other names: Niaspan;Drug: aspirin (ASA)<br>* 325 mg tablets administered once daily<br>* Other names: acetylsalicylic acid;Drug: aspirin placebo (ASA Pbo)<br>* Tablets administered once daily<br>* Other names: placebo;|
| Experimental: NER 500; ASA Pbo run-in, ASA Pbo coadmin<br>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)<br>* Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period<br>* Other names: Niaspan;Drug: aspirin placebo (ASA Pbo)<br>* Tablets administered once daily<br>* Other names: placebo;|
| Experimental: NER 1000; ASA run-in, ASA coadmin<br>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)<br>* Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period<br>* Other names: Niaspan;Drug: aspirin (ASA)<br>* 325 mg tablets administered once daily<br>* Other names: acetylsalicylic acid;|
| Experimental: NER 1000; ASA Pbo run-in, ASA coadmin<br>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)<br>* Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period<br>* Other names: Niaspan;Drug: aspirin (ASA)<br>* 325 mg tablets administered once daily<br>* Other names: acetylsalicylic acid;Drug: aspirin placebo (ASA Pbo)<br>* Tablets administered once daily<br>* Other names: placebo;|
| Experimental: NER 1000; ASA Pbo run-in, ASA Pbo coadmin<br>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)<br>* Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period<br>* Other names: Niaspan;Drug: aspirin placebo (ASA Pbo)<br>* Tablets administered once daily<br>* Other names: placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | 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. | From Baseline to end of Week 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 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. | 4 weeks | 
| Mean of Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 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. | 4 weeks | 
| Mean Number of Moderate or Greater Flushing Events Per Subject Per Week Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 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. | 4 weeks |