Improved control of niacin-induced flushing using an optimized once-daily, extended-release niacin formulation.
BACKGROUND
Niacin is a recognized treatment for dyslipidemia due to its favorable effects on all lipid parameters. However, the clinical use of niacin has been limited by its adverse effects, particularly cutaneous flushing. A newly reformulated 1,000 mg niacin ER tablet has been designed to reduce flushing relative to the original commercial niacin ER formulation. The aim of this study is to compare the incidence, intensity and duration of flushing between the 1,000 mg reformulated niacin ER and the 1,000 mg commercially available formulation, when administered as a single 2,000 mg dose to healthy male volunteers.


METHODS
This was a double-blind, double-dummy, placebo-controlled, 3-way crossover, flush provocation study conducted at a single center. To increase the probability of flushing, subjects were administered niacin ER at the upper limit of the approved dosage range (2,000 mg), and were precluded from using aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) during the study. Subjects received reformulated niacin ER, commercial niacin ER or placebo in a 3-way crossover fashion. The primary flushing variable was the occurrence of a flushing event. Secondary flushing variables included the number of flushing episodes, intensity and duration of flushing for both overall flushing events and for individual symptoms of flushing (redness, warmth, tingling and itching).


RESULTS
A total of 156 subjects were enrolled in the study. Of 133 subjects who received at least 1 dose of study medication in at least 2 study periods, 89% of subjects experienced flushing during treatment with reformulated niacin ER, and 98% of subjects experienced flushing during treatment with commercial niacin ER. This difference was statistically significant (p - 0.0027). Reformulated niacin ER resulted in a 42% reduction in median flush intensity (p < 0.0001) and a 43% reduction in median flush duration (p < 0.0001) relative to commercial niacin ER. The duration of first flushing event was more than 1 hour shorter with reformulated niacin ER. During the study, 29% of subjects (45/156) experienced treatment-emergent adverse events, which were mostly mild in intensity and considered to be remotely related or unrelated to the study drug.


CONCLUSIONS
The 1,000 mg reformulated niacin ER tablet substantially decreases the incidence, intensity and duration of flushing relative to the commercially available 1,000 mg niacin ER tablet, and represents an improved niacin therapy option.
Cefali
E A
EA
Kos Pharmaceuticals, Inc., Cranbury, NJ, USA. gcefali@kospharm.com
Simmons
P D
PD
Stanek
E J
EJ
Shamp
T R
TR
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005483:Flushing / Q000139:chemically induced / Q000517:prevention & control*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009525:Niacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010352:Patient Dropouts; D011537:Pruritus / Q000139:chemically induced; D013607:Tablets; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D013607:Tablets; D009525:Niacin