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Articles by Darbie Maccubbin
Total Records ( 5 ) for Darbie Maccubbin
  Debra Kush , Hyo-Soo Kim , Da Yi Hu , Ji Liu , Waheeda Sirah , Aditi Sapre , Christine McCrary , John F. Paolini and Darbie Maccubbin
 

Background
Niacin has proven lipid-modifying efficacy and cardiovascular benefit; however, it is underused because of skin flushing, a process mediated primarily by prostaglandin D2 (PGD2). Laropiprant (LRPT), a PGD2 receptor (DP1) antagonist that mitigates niacin-induced flushing, has been combined with extended-release niacin (ERN) into a fixed-dose tablet containing 1 g of ERN and 20 mg of LRPT (ERN/LRPT 1 g). In a large-scale (n = not, vert, similar1600), multinational, 6-month study in dyslipidemic patients, ERN/LRPT 2 g produced superior lipid-modifying efficacy vs placebo, whether administered alone or with concomitant statins.

Objective
This Phase III, randomized, double-blind study evaluated the lipid-modifying efficacy of ERN/LRPT alone or added to ongoing statins in Asian patients with primary hypercholesterolemia or mixed hyperlipidemia.

Methods
After a 4-week placebo run-in, patients were randomized to ERN/LRPT 1 g (n = 322) or placebo (PBO; n = 324). After 4 weeks, the dose was advanced to 2 tablets/d (ERN/LRPT 2 g or PBO) for 8 additional weeks. End points included effects of ERN/LRPT 2 g vs PBO on low-density lipoprotein cholesterol (LDL-C; primary), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and other lipids/lipoproteins.

Results
Relative to PBO, ERN/LRPT 2 g produced significant (P < .001) changes in LDL-C (−14.7%), HDL-C (15.9%), TG (−23.4%), LDL-C:HDL-C (−25.5%), non-HDL-C (−16.4%), apolipoprotein (Apo) B (−15.4%), and Apo A-I (5.3%) from baseline to week 12 in the total population. Similar results were observed in patients treated with ERN/LRPT alone or added to ongoing statin.

Conclusion
ERN/LRPT 2 g, administered alone or with a statin, produced significant improvements in multiple lipid/lipoprotein parameters in dyslipidemic Asian patients.

  Harold E. Bays , Arvind Shah , Jianxin Lin , Christine McCrary Sisk , John F. Paolini and Darbie Maccubbin
 

Objective

Patients with metabolic syndrome (MetS) are at increased risk for cardiovascular disease. Niacin improves lipid abnormalities associated with MetS, but is underused, mainly because of flushing. Laropiprant (LRPT) reduces niacin-induced flushing and, in combination with extended-release niacin (ERN/LRPT), improves lipid levels.

Methods

In this post-hoc subgroup analysis of a phase 3 randomized, double-blind, placebo-controlled, 24-week study (n = 1613), we evaluated the efficacy and safety of ERN/LRPT in dyslipidemic patients with MetS. Dyslipidemic patients were randomized 3:2:1 to ERN/LRPT 1 g, ERN 1 g, or placebo. After 4 weeks, active treatment doses were doubled (2 tablets) for 20 weeks.

Results

Relative to placebo, ERN/LRPT significantly lowered low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol levels to a similar degree in MetS and non-MetS cohorts. ERN/LRPT significantly (P < .001) lowered triglyceride levels versus placebo in patients with MetS and without MetS (−30.2% vs −22.2%, respectively). The between subgroup difference in triglyceride lowering was not significant. For all lipid parameters, ERN/LRPT and ERN produced similar magnitude changes. ERN/LRPT and ERN produced similar increases in median fasting blood glucose levels versus placebo in patients with MetS (2.0 and 4.0 mg/dL, respectively) and without MetS (4.0 mg/dL for both groups), consistent with a known effect of niacin.

Conclusion

In patients with MetS, ERN/LRPT improves multiple lipid parameters associated with increased cardiovascular disease risk. ERN/LRPT numerically improved triglyceride levels more in patients with versus without MetS, which is likely related to greater baseline triglycerides in MetS patients.

  Andrew G. Bostom , Alexandra A. MacLean , Darbie Maccubbin , Diane Tipping , Hilde Giezek and William A. Hanlon
 

Background

Niacin compounds lower serum phosphorus concentrations in patients with end-stage renal disease.

Methodology

We evaluated the impact of extended release niacin, given in fixed-dose combination with laropiprant, a specific inhibitor of prostaglandin-mediated, niacin-induced flushing, versus placebo, on serum phosphorus concentrations measured serially (at weeks 0, 4, 8, 12, 18, 24, 30, and 36) during a 36-week randomized, controlled trial. All subjects had a confirmed diagnosis of type 2 diabetes (n = 446 niacin/laropiprant; n = 339 placebo). Estimated glomerular filtration rate ranged from 36 to 184 mL/min/1.73 m2, with n = 111 (14.1%) having a value <60 mL/min/1.73 m2. Subjects received one tablet daily of extended-release niacin/laropiprant (1g niacin/ 20 mg laropiprant) for the first 4 weeks, and 2 tablets once daily, thereafter, or matched placebo. Niacin lowered serum phosphorus concentrations by 0.36 mg/dL (95% CI: −0.40, −0.31; P < .001), relative to placebo, from baseline values of 3.57 and 3.56 mg/dL in the niacin and placebo groups, respectively. Subgroup analyses revealed no evidence for phosphorus-lowering effect modification by these baseline variables: glomerular filtration rate <60 (n = 111;14.1%) vs ≥60 mL/min/m2 (n = 674; 85.9%); phosphorus ≤3.5 mg/dL (n = 392; 49.9%) vs >3.5 mg/dL (n = 393; 50.1%); or prior statin use (n = 618; 78.7%) vs nonuse (n = 167; 21.3%).

Conclusions and Implications

These data confirm that niacin's phosphorus-lowering effects-which may have therapeutic implications for the management of hyperphosphatemia and possible prevention of cardiorenal outcomes in renal disease-extend across a broad spectrum of renal function in type 2 diabetics without stage 4 or 5 chronic kidney disease (a glomerular filtration rate ≥30 mL/min/1.73 m2).

  James McKenney , Harold Bays , Michael Koren , Christie M. Ballantyne , John F. Paolini , Yale Mitchel , Abigaile Betteridge , Olga Kuznetsova , Aditi Sapre , Christine McCrary Sisk and Darbie Maccubbin
 

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 ≥3x 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.

Conclusion

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.

  Harold E. Bays , Eliot A. Brinton , Joseph Triscari , Erluo Chen , Darbie Maccubbin , Alexandra MacLean , Kendra Gibson , Amy O. Johnson-Levonas and Yale B. Mitchel
  The degree of glycemic control may alter lipid levels, which might also alter treatment efficacy of lipid agents.
 
 
 
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