Dyslipidemia
Conditions
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.
Interventions
Tablets administered once daily; titrated to 2000 mg maximum dose during coadministration period
DRUGaspirin (ASA)
325 mg tablets administered once daily
DRUGaspirin placebo (ASA Pbo)
Tablets administered once daily
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 |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 47 study sites in the United States between February and April, 2008.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| NER 500; ASA run-in, ASA Coadmin 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) | 44 |
| NER 500; ASA Pbo run-in, ASA Coadmin 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) | 43 |
| 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 (4 weeks) | 41 |
| NER 1000; ASA run-in, ASA Coadmin 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) | 43 |
| NER 1000; ASA Pbo run-in, ASA Coadmin 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) | 41 |
| 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 (4 weeks) | 44 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Coadministration Period | Adverse Event | 3 | 1 | 7 | 4 | 3 | 4 |
| Coadministration Period | Other | 0 | 2 | 3 | 1 | 1 | 1 |
| Coadministration Period | Protocol Violation | 0 | 1 | 0 | 1 | 1 | 0 |
| Coadministration Period | Withdrawal by Subject | 1 | 1 | 0 | 1 | 0 | 1 |
| Run-in Period | Adverse Event | 0 | 0 | 1 | 0 | 1 | 0 |
| Run-in Period | Noncompliance | 1 | 0 | 1 | 0 | 0 | 0 |
| Run-in Period | Withdrawal by Subject | 0 | 1 | 1 | 1 | 3 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|
| Age Continuous | 55.5 Years STANDARD_DEVIATION 10.62 | 49.0 Years STANDARD_DEVIATION 10.48 | 51.5 Years STANDARD_DEVIATION 12.58 | 53.7 Years STANDARD_DEVIATION 12.4 | 54.8 Years STANDARD_DEVIATION 11.08 | 52.3 Years STANDARD_DEVIATION 12.45 | 52.8 Years STANDARD_DEVIATION 11.73 |
| Region of Enrollment United States | 44 participants | 43 participants | 41 participants | 43 participants | 41 participants | 44 participants | 256.0 participants |
| Sex: Female, Male Female | 21 Participants | 23 Participants | 21 Participants | 15 Participants | 21 Participants | 23 Participants | 124.0 Participants |
| Sex: Female, Male Male | 23 Participants | 20 Participants | 20 Participants | 28 Participants | 20 Participants | 21 Participants | 132.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 119 / — | 72 / — |
| serious Total, serious adverse events | 1 / — | 1 / — |
Outcome results
Primary
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.
Time frame: From Baseline to end of Week 1
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | None | 57 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Mild | 28 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | None/mild | 85 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Moderate | 11 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Severe | 4 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Very severe | 1 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Severe | 8 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | None | 48 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Moderate | 17 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Mild | 24 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | Very severe | 4 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events During Week 1 of Niacin Extended-release (NER) Treatment | None/mild | 71 Percentage of Subjects |
p-value: 0.01Cochran-Mantel-Haenszel
Secondary
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.
Time frame: 4 weeks
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | None | 30 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Mild | 28 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | None/Mild | 58 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Moderate | 28 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Severe | 11 Percentage of Subjects |
| Any Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Very severe | 4 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Severe | 23 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | None | 15 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Moderate | 35 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Mild | 14 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | Very severe | 13 Percentage of Subjects |
| No Acetylsalicylic Acid | Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | None/Mild | 30 Percentage of Subjects |
Secondary
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.
Time frame: 4 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Any Acetylsalicylic Acid | Mean Number of Moderate or Greater Flushing Events Per Subject Per Week Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 0.3 Number of Events per Subject per Week | Standard Deviation 0.64 |
| No Acetylsalicylic Acid | Mean Number of Moderate or Greater Flushing Events Per Subject Per Week Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 0.8 Number of Events per Subject per Week | Standard Deviation 1.1 |
Secondary
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.
Time frame: 4 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Any Acetylsalicylic Acid | Mean of Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 3.1 Scores on a Scale | Standard Deviation 2.86 |
| No Acetylsalicylic Acid | Mean of Maximum Severity of Flushing Events Overall During 4 Weeks of Niacin Extended-release (NER) Treatment | 5.1 Scores on a Scale | Standard Deviation 3.16 |