Dyslipidemia
Conditions
Brief summary
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
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.
Interventions
Tablets administered once daily for 6 weeks; titrated to a maximum dose of 2000 mg
DRUGNiacin extended-release (NER) placebo
Tablets administered once daily for 6 weeks
DRUGAspirin (ASA)
Tablets (325 mg) administered once daily for 6 weeks
DRUGAspirin (ASA) placebo
Tablets administered once daily for 6 weeks
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FAST Responsiveness--maximum Flushing Severity Score | Study start to Day 43 | 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. |
| Flushing ASsessment Tool (FAST) Test-retest Reliability--mean Flushing Severity Score | Week 1 to Week 2 | 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. |
| FAST Test-retest Reliability--maximum Flushing Severity Score | Week 1 to Week 2 | 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. |
| FAST Cross-sectional Construct Validity--mean Flushing Severity Score | Week 1 | 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. |
| FAST Cross-sectional Construct Validity--maximum Flushing Severity Score | Week 1 | 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. |
| FAST Longitudinal Construct Validity--mean Flushing Severity Score | Week 1 to Week 2 | 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). |
| FAST Longitudinal Construct Validity--maximum Flushing Severity Score | Week 1 to Week 2 | 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). |
| FAST Responsiveness--mean Flushing Severity Score | Study start to Day 43 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Severity of Flushing Events Overall During the Study | Week 1 to Week 6 | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at 41 sites in the United States between February and June, 2008.
Pre-assignment details
Of the 276 subjects that were randomized, 5 discontinued from the study prior to receiving study drug due to withdrawal of consent (2), death in the family (1), positive pregnancy test (1), and lost to follow up (1).
Participants by arm
| Arm | Count |
|---|---|
| NER/ASA Niacin extended-release (NER) titrated to 2000 mg plus aspirin (ASA) 325 mg once daily | 91 |
| NER/ASA Placebo Niacin extended-release (NER) titrated to 2000 mg plus aspirin (ASA) placebo once daily | 90 |
| NER Placebo/ASA Placebo Niacin extended-release (NER) placebo plus aspirin (ASA) placebo once daily | 90 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 8 | 7 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 |
| Overall Study | Noncompliance | 2 | 3 | 1 |
| Overall Study | Personal reasons | 0 | 0 | 1 |
| Overall Study | Protocol violation | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 0 |
Baseline characteristics
| Characteristic | NER/ASA | NER/ASA Placebo | NER Placebo/ASA Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 54.1 years STANDARD_DEVIATION 11.68 | 53.7 years STANDARD_DEVIATION 12.74 | 52.9 years STANDARD_DEVIATION 12.26 | 53.6 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment United States | 91 participants | 90 participants | 90 participants | 271 participants |
| Sex: Female, Male Female | 42 Participants | 41 Participants | 42 Participants | 125 Participants |
| Sex: Female, Male Male | 49 Participants | 49 Participants | 48 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 74 / — | 80 / — | 60 / — |
| serious Total, serious adverse events | 1 / — | 1 / — | 2 / — |
Outcome results
Primary
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.
Time frame: Week 1
Population: m-ITT population, defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 entry in the e-diary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Cross-sectional Construct Validity--maximum Flushing Severity Score | 0.66 Spearman correlation coefficient |
p-value: <0.0001Spearman rank-order correlation
Primary
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.
Time frame: Week 1
Population: m-ITT population, defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 entry in the e-diary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Cross-sectional Construct Validity--mean Flushing Severity Score | 0.64 Spearman correlation coefficient |
p-value: <0.0001Spearman rank-order correlation
Primary
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).
Time frame: Week 1 to Week 2
Population: m-ITT population, defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 entry in the e-diary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Longitudinal Construct Validity--maximum Flushing Severity Score | -0.42 Spearman correlation coefficient |
p-value: <0.0001Spearman rank-order correlation
Primary
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).
Time frame: Week 1 to Week 2
Population: m-ITT population, defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 entry in the e-diary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Longitudinal Construct Validity--mean Flushing Severity Score | -0.44 Spearman correlation coefficient |
p-value: <0.0001Spearman rank-order correlation
Primary
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.
Time frame: Study start to Day 43
Population: Subjects in the m-ITT population were classified as responders (improved flushing symptoms) or nonresponders (no change or worsened flushing symptoms) based on changes in flushing symptoms from study start to Day 43.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Responsiveness--maximum Flushing Severity Score | -1.85 Units on a scale |
| NER/ASA Placebo | FAST Responsiveness--maximum Flushing Severity Score | -0.18 Units on a scale |
p-value: <0.001Independent groups t-test
Primary
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.
Time frame: Study start to Day 43
Population: Subjects in the m-ITT population were classified as responders (improved flushing symptoms) or nonresponders (no change or worsened flushing symptoms) based on changes in flushing symptoms from study start to Day 43.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Responsiveness--mean Flushing Severity Score | -0.51 Units on a scale |
| NER/ASA Placebo | FAST Responsiveness--mean Flushing Severity Score | 0.15 Units on a scale |
p-value: 0.002Independent groups t-test
Primary
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.
Time frame: Week 1 to Week 2
Population: Subjects with stable flushing symptoms from Week 1 to Week 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | FAST Test-retest Reliability--maximum Flushing Severity Score | 0.40 Intraclass correlation coefficient |
Primary
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.
Time frame: Week 1 to Week 2
Population: Subjects with stable flushing symptoms from Week 1 to Week 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects With Stable Flushing Symptoms | Flushing ASsessment Tool (FAST) Test-retest Reliability--mean Flushing Severity Score | 0.75 Intraclass correlation coefficient |
Secondary
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.
Time frame: Week 1 to Week 6
Population: m-ITT population, defined as all randomized subjects who received at least 1 dose of study drug and who had at least 1 entry in the e-diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subjects With Stable Flushing Symptoms | Maximum Severity of Flushing Events Overall During the Study | None | 26 Percentage of subjects |
| Subjects With Stable Flushing Symptoms | Maximum Severity of Flushing Events Overall During the Study | Mild | 23 Percentage of subjects |
| Subjects With Stable Flushing Symptoms | Maximum Severity of Flushing Events Overall During the Study | None/Mild | 49 Percentage of subjects |
| Subjects With Stable Flushing Symptoms | Maximum Severity of Flushing Events Overall During the Study | Moderate | 34 Percentage of subjects |
| Subjects With Stable Flushing Symptoms | Maximum Severity of Flushing Events Overall During the Study | Severe | 17 Percentage of subjects |
| Subjects With Stable Flushing Symptoms | Maximum Severity of Flushing Events Overall During the Study | Very Severe | 0 Percentage of subjects |
| NER/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Very Severe | 7 Percentage of subjects |
| NER/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | None | 14 Percentage of subjects |
| NER/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Moderate | 31 Percentage of subjects |
| NER/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Severe | 32 Percentage of subjects |
| NER/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Mild | 16 Percentage of subjects |
| NER/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | None/Mild | 30 Percentage of subjects |
| NER Placebo/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Mild | 38 Percentage of subjects |
| NER Placebo/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | None/Mild | 75 Percentage of subjects |
| NER Placebo/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Very Severe | 0 Percentage of subjects |
| NER Placebo/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Moderate | 22 Percentage of subjects |
| NER Placebo/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | None | 37 Percentage of subjects |
| NER Placebo/ASA Placebo | Maximum Severity of Flushing Events Overall During the Study | Severe | 2 Percentage of subjects |
p-value: <0.001Cochran-Mantel-Haenszel