Safety of extended-release niacin/laropiprant in patients with dyslipidemia.
OBJECTIVE
To evaluate the safety profile of extended-release niacin/laropiprant (ERN/LRPT), pooling data from studies in the clinical development program.


METHODS
Data were pooled from three active- or placebo-controlled phase 3 studies and three 1-year extensions of phase 2 studies that ranged from 12 to 52 weeks (N = 4747): ERN/LRPT = 2548; ERN or Niaspan® (ERN-NSP = 1268); or simvastatin or placebo (SIMVA-PBO = 931).


RESULTS
The safety and tolerability profile for ERN/LRPT was similar to that of ERN-NSP, except for fewer flushing-related adverse experiences and discontinuations with ERN/LRPT than ERN-NSP. The incidence of consecutive ≥3× the upper limit of normal increases in alanine aminotransferase and/or aspartate aminotransferase was numerically (but not statistically) greater with ERN/LRPT (1.0%) than ERN-NSP (0.5%) and similar to SIMVA-PBO (0.9%). Elevations were reversible with therapy discontinuation and not associated with clinical hepatotoxicity. There was no evidence that ERN/LRPT administered alone or concurrently with a statin had adverse effects on muscle. ERN/LRPT and ERN-NSP produced small median increases in fasting blood glucose levels (∼4 mg/dL) after 24 weeks of treatment, consistent with known effects of niacin.


CONCLUSIONS
The favorable safety and tolerability profile of ERN/LRPT for up to 1 year supports the use of LRPT to achieve improved therapeutic dosing of niacin, an agent with comprehensive lipid-modifying efficacy and shown to reduce cardiovascular risk.
National Clinical Research Inc., 2809 Emerywood Parkway, Suite 140, Richmond, VA 23294, USA. jmckenney@ncrinc.net
James
J
McKenney
Harold
H
Bays
Michael
M
Koren
Christie M
CM
Ballantyne
John F
JF
Paolini
Yale
Y
Mitchel
Abigaile
A
Betteridge
Olga
O
Kuznetsova
Aditi
A
Sapre
Christine McCrary
CM
Sisk
Darbie
D
Maccubbin
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003692:Delayed-Action Preparations; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects*; D010349:Patient Compliance; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D011982:Receptors, Prostaglandin; C501562:prostanoid D receptor 1, human; D009525:Niacin