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

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

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: niacin extended-release (NER); Drug: aspirin (ASA); Drug: aspirin placebo (ASA Pbo)

• Study Type: Interventional
• Enrollment (Actual): 277
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
  • Arizona
    • Scottsdale, Arizona, United States, 85251
    • Tucson, Arizona, United States, 85712
    • Tucson, Arizona, United States, 85710
  • California
    • Anaheim, California, United States, 92801
    • Los Angeles, California, United States, 90057
    • Newport Beach, California, United States, 92660
    • Stockton, California, United States, 95204
    • Vista, California, United States, 90057
    • Westlake Village, California, United States, 91361
  • Florida
    • Coral Gables, Florida, United States, 33134
    • Jacksonville, Florida, United States, 32259
    • Miami, Florida, United States, 33186
    • Pembroke Pines, Florida, United States, 33027
    • West Palm Beach, Florida, United States, 33407
  • Massachusetts
    • N. Dartmouth, Massachusetts, United States, 02747
  • New York
    • Rochester, New York, United States, 14609
  • North Carolina
    • Charlotte, North Carolina, United States, 28262
    • Winston-Salem, North Carolina, United States, 27103
  • Pennsylvania
    • Penndel, Pennsylvania, United States, 19047
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
    • Simpsonville, South Carolina, United States, 29681
  • Texas
    • Colleyville, Texas, United States, 76034
    • Houston, Texas, United States, 77074
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / 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

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

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Roopal Thakkar, MD, Abbott

Publications and helpful links

General Publications

• Thakkar RB, Kashyap ML, Lewin AJ, Krause SL, Jiang P, Padley RJ. Acetylsalicylic acid reduces niacin extended-release-induced flushing in patients with dyslipidemia. Am J Cardiovasc Drugs. 2009;9(2):69-79. doi: 10.1007/BF03256578.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: February 21, 2008
• First Submitted That Met QC Criteria: February 21, 2008
• First Posted (Estimate): February 29, 2008

Study Record Updates

• Last Update Posted (Estimate): September 2, 2009
• Last Update Submitted That Met QC Criteria: August 26, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Skin Manifestations; Dyslipidemias; Flushing; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Aspirin; Niacin
• Other Study ID Numbers: M10-241