Evaluation of a Flushing ASsessment Tool (FAST) in Subjects Receiving Niacin Extended-release Plus Aspirin

Study Overview
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Brief Summary
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The primary purpose of this study was to evaluate the psychometric characteristics (reliability, validity, and responsiveness) of a Flushing ASsessment Tool (FAST) in subjects receiving niacin extended-release (NER) plus aspirin (ASA) daily for 6 weeks. The FAST is a questionnaire that was developed to provide a detailed assessment of flushing symptoms and their impact in patients receiving niacin therapy. The effect of aspirin on flushing symptoms, as measured by the FAST, was also evaluated.

Detailed Description
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This study was designed to evaluate the psychometric characteristics of the FAST questionnaire. The FAST is a self-administered questionnaire, completed using a hand-held electronic data capture device (LogPad e-diary). Subjects recorded the start and stop date and time of each flushing event, the presence and severity of individual flushing symptoms (redness, warmth, tingling and/or itching), and an overall assessment of their flushing experience. Evaluation of the psychometric characteristics of the FAST was based on 3 primary data analyses: 1 ) test-retest reliability based on the intraclass correlation coefficient; 2) construct validity based on Spearman correlation coefficients; and 3) responsiveness based on changes in FAST scores. The mean and maximum severity of flushing events, as measured by the FAST, were the primary variables evaluated in each of the 3 data analyses mentioned above. Psychometric analyses were performed blinded to treatment group assignment.

Official Title
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A Randomized, Double-blind, Parallel, Multicenter, Placebo-controlled, Prospective Study to Evaluate the Functionality of the Flushing ASsessment Tool (FAST) in Subjects Administered Niaspan® Plus Acetylsalicylic Acid (ASA), Niaspan® Plus ASA Placebo or Niaspan® Placebo Plus ASA Placebo Daily for Six Weeks

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: Niacin extended-release (NER)
* Drug: Niacin extended-release (NER) placebo
* Drug: Aspirin (ASA)
* Drug: Aspirin (ASA) placebo


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NER/ASA<br> | Drug: Niacin extended-release (NER)<br>* Tablets administered once daily for 6 weeks; titrated to a maximum dose of 2000 mg<br>* Other names: Niaspan;Drug: Aspirin (ASA)<br>* Tablets (325 mg) administered once daily for 6 weeks<br>* Other names: acetylsalicylic acid;|
| Experimental: NER/ASA Placebo<br> | Drug: Niacin extended-release (NER)<br>* Tablets administered once daily for 6 weeks; titrated to a maximum dose of 2000 mg<br>* Other names: Niaspan;Drug: Aspirin (ASA) placebo<br>* Tablets administered once daily for 6 weeks<br>|
| Experimental: NER Placebo/ASA Placebo<br> | Drug: Niacin extended-release (NER) placebo<br>* Tablets administered once daily for 6 weeks<br>Drug: Aspirin (ASA) placebo<br>* Tablets administered once daily for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flushing ASsessment Tool (FAST) Test-retest Reliability--mean Flushing Severity Score | Test-retest reliability of the mean flushing severity score was evaluated. The intraclass correlation coefficient comparing flushing severity scores for Week 1 and Week 2 was examined to determine test-retest reliability. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. | Week 1 to Week 2 | 
| FAST Test-retest Reliability--maximum Flushing Severity Score | Test-retest reliability of the maximum flushing severity score was evaluated. The intraclass correlation coefficient comparing flushing severity scores for Week 1 and Week 2 was examined to determine test-retest reliability. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. | Week 1 to Week 2 | 
| FAST Cross-sectional Construct Validity--mean Flushing Severity Score | The relationship between mean flushing severity and overall flushing troublesomeness was evaluated by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Overall flushing troublesomeness was assessed using the FAST on a scale of 1 to 10, with 10 being the most troublesome. | Week 1 | 
| FAST Cross-sectional Construct Validity--maximum Flushing Severity Score | The relationship between maximum flushing severity and overall flushing troublesomeness was evaluated by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Overall flushing troublesomeness was assessed using the FAST on a scale of 1 to 10, with 10 being the most troublesome. | Week 1 | 
| FAST Longitudinal Construct Validity--mean Flushing Severity Score | The relationship between the change in mean flushing severity scores from Week 1 to Week 2, and the subject-rated overall treatment effect scale administered at Week 2, was assessed by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. The overall treatment effect was assessed on a scale of 1 (symptoms are worse since study start), 2 (symptoms are about the same since study start), or 3 (symptoms are better since study start). | Week 1 to Week 2 | 
| FAST Longitudinal Construct Validity--maximum Flushing Severity Score | The relationship between the change in maximum flushing severity scores from Week 1 to Week 2, and the subject-rated overall treatment effect scale administered at Week 2, was assessed by examining the Spearman rank-order correlation. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. The overall treatment effect was assessed on a scale of 1 (symptoms are worse since study start), 2 (symptoms are about the same since study start), or 3 (symptoms are better since study start). | Week 1 to Week 2 | 
| FAST Responsiveness--mean Flushing Severity Score | The change in mean flushing severity scores from study start to Day 43 was compared in subjects classified as responders vs. nonresponders. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Changes in mean flushing severity scores were negative if flushing symptoms improved and positive if flushing symptoms worsened. | Study start to Day 43 | 
| FAST Responsiveness--maximum Flushing Severity Score | The change in maximum flushing severity scores from study start to Day 43 was compared in subjects classified as responders vs. nonresponders. Flushing severity was assessed using the FAST on a scale of 1 to 10, with 10 being the most severe. Changes in maximum flushing severity scores were negative if flushing symptoms improved and positive if flushing symptoms worsened. | Study start to Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Severity of Flushing Events Overall During the Study | The severity of flushing events was assessed as none, mild, moderate, severe, or very severe using the FAST. The maximum severity of flushing events overall during the study was compared among treatment groups. | Week 1 to Week 6 |