Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial

Papp, Kim; Cather, Jennifer Clay; Rosoph, Les; Sofen, Howard; Langley, Richard; Matheson, Robert; Hu, ChiaChi; Day, Robert M.

doi:10.1016/s0140-6736(12)60642-4

Cited by 238 publications

(220 citation statements)

References 17 publications

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“…The most commonly reported AEs (nervous system disorders such as dizziness and headache) are consistent with those observed in clinical studies 10, 12, 27. A number of AEs were considered to be related to underlying renal impairment.…”

Section: Discussionsupporting

confidence: 86%

Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12

Liu¹,

Zhou²,

Assaf³

et al. 2016

Clinical Pharm in Drug Dev

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The pharmacokinetics of apremilast and its major metabolite M12 were evaluated in subjects with varying degrees of renal impairment. Men and women with renal impairment (estimated glomerular filtration rate, 60‒89 mL/min [mild, n = 8], 30‒59 mL/min [moderate, n = 8], or <30 mL/min [severe, n = 8]) or demographically healthy matched (control) subjects (n = 24) received a single oral dose of apremilast 30 mg. Plasma apremilast and metabolite M12 concentrations were determined, and pharmacokinetic parameters were calculated from samples obtained predose and up to 72 hours postdose. In subjects with mild to moderate renal impairment, apremilast pharmacokinetic profiles were similar to healthy matched subjects. In subjects with severe renal impairment, apremilast elimination was significantly slower, and exposures based on area under the plasma concentration‐versus‐time curve from time zero extrapolated to infinity and maximum observed plasma concentration were increased versus healthy matched subjects. Metabolite M12 pharmacokinetic profiles for subjects with mild renal impairment were similar to those of the healthy matched subjects; however, they were increased in both the moderate and severe renally impaired subjects. Dose reduction of apremilast is recommended in individuals with severe renal impairment, but not in those with mild to moderate renal impairment.

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Section: Discussionsupporting

confidence: 86%

Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12

Liu¹,

Zhou²,

Assaf³

et al. 2016

Clinical Pharm in Drug Dev

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show abstract

“…8) For the nature of chronic diseases, a long term treatment for psoriatic arthritis and plaque psoriasis with apremilast is generally recommended. 5) Tolerability or dose regimen issues possess limitations which may significantly impair patient compliance and therefore overall efficacy of treatment. Thus, an alternative drug delivery system is urgently needed to improve the poor tolerability and the need for frequent daily dosing during long-term regimen with IR formulations.…”

Section: )mentioning

confidence: 99%

“…3) Unlike tumor necrosis factor (TNF)-α inhibitors, which bind directly to TNF-α, apremilast causes a broad inhibition of multiple pro-inflammatory mediators such as interleukin (IL)-6, IL-10 and TNF-α, 4,5) exerting therefore an overall anti-inflammatory effect.…”

mentioning

confidence: 99%

Development of an Extended-Release Formulation for Apremilast and a Level A <i>in Vitro</i>–<i>in Vivo</i> Correlation Study in Beagle Dogs

Tang

Shigui

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The primary objective of the present study was to develop extended-release matrix formulations of apremilast for the oral delivery and to study their in vitro and in vivo correlation. Five extended-release formulations containing hydroxypropylmethylcellulose (HPMC) as the retarding excipient with different release rate of apremilast were prepared. Dissolution tests of all the formulated tablets were performed in water, pH 4.0 and 6.8 buffer solutions. The in vitro release kinetics was studied and supported by Korsmeyer-Peppas's equation as it presented highest values of correlation coefficients (r 2 up to 0.966). Among all formulated tablets, F2 (HPMC 25%) and F4 (HPMC 35%) were selected to perform an in vivo study in beagle dogs to obtain various pharmacokinetic parameters, i.e., peak plasma concentration (C max ), time to peak plasma concentration (t max ), area under the plasma-concentration vs. time curve (AUC). Higher t max and t 1/2 , lower C max and elimination coefficient (K e ) were observed for both extended formulations compared to marketed immediate-release products (Otezla ® ). Level A in vitro-in vivo correlations were created with the help of Wagner-Nelson and numeric deconvolution methods. Both formulations showed good in vitro-in vivo correlations whose accuracies were further verified by an internal validation.

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“…[1][2][3] In general, patients were heavily pre-treated (2−4 previous therapies) and their median ages were 66−68 years. Patients taking warfarin were excluded.…”

Section: New Drugsmentioning

confidence: 99%

“…The approval is based on a single-arm phase II trial 1 and a comparative phase III trial with ofatumumab. 2 Most enrolled patients had chronic lymphocytic leukaemia with only 5% having small lymphocytic lymphoma.…”

Section: Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphomamentioning

confidence: 99%

New drugs: Apremilast

2015

Aust Prescr

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Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial

Cited by 238 publications

References 17 publications

Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12

Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12

Development of an Extended-Release Formulation for Apremilast and a Level A <i>in Vitro</i>–<i>in Vivo</i> Correlation Study in Beagle Dogs

New drugs: Apremilast

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