OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study

Jon Hanifin, Charles N. Ellis, Ilona J. Frieden, Regina Fölster-Holst, Linda F. Stein Gold, Angelo Secci, Angela J. Smith, Cathy Zhao, Elena Kornyeyeva, Lawrence F. Eichenfield

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. Objectives: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. Methods: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks. Results: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. Limitations: Further confirmatory phase-III studies are required. Conclusion: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.

Original languageEnglish (US)
JournalJournal of the American Academy of Dermatology
DOIs
StateAccepted/In press - 2016

Fingerprint

Phosphodiesterase 4 Inhibitors
Atopic Dermatitis
Placebos
Type 4 Cyclic Nucleotide Phosphodiesterase
Eczema
Therapeutics
Pruritus
Ointments
Visual Analog Scale
Leukocytes
Research Personnel
Incidence

Keywords

  • Atopic dermatitis
  • Atopic eczema
  • OPA-15406
  • Phosphodiesterase type 4 inhibitor
  • Topical agents
  • Topical calcineurin inhibitor

ASJC Scopus subject areas

  • Dermatology

Cite this

OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD) : A phase-II randomized, double-blind, placebo-controlled study. / Hanifin, Jon; Ellis, Charles N.; Frieden, Ilona J.; Fölster-Holst, Regina; Stein Gold, Linda F.; Secci, Angelo; Smith, Angela J.; Zhao, Cathy; Kornyeyeva, Elena; Eichenfield, Lawrence F.

In: Journal of the American Academy of Dermatology, 2016.

Research output: Contribution to journalArticle

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title = "OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study",
abstract = "Background: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. Objectives: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. Methods: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3{\%} (n = 41), OPA-15406 1{\%} (n = 43), or vehicle (n = 37) twice daily for 8 weeks. Results: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1{\%} group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1{\%} was notable in week 1 (31.4{\%} vs 6.0{\%} for vehicle; P = .0005), even larger in week 2 (39.0{\%} vs 3.0{\%}; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1{\%} group (36.4{\%} mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. Limitations: Further confirmatory phase-III studies are required. Conclusion: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.",
keywords = "Atopic dermatitis, Atopic eczema, OPA-15406, Phosphodiesterase type 4 inhibitor, Topical agents, Topical calcineurin inhibitor",
author = "Jon Hanifin and Ellis, {Charles N.} and Frieden, {Ilona J.} and Regina F{\"o}lster-Holst and {Stein Gold}, {Linda F.} and Angelo Secci and Smith, {Angela J.} and Cathy Zhao and Elena Kornyeyeva and Eichenfield, {Lawrence F.}",
year = "2016",
doi = "10.1016/j.jaad.2016.04.001",
language = "English (US)",
journal = "Journal of the American Academy of Dermatology",
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T1 - OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD)

T2 - A phase-II randomized, double-blind, placebo-controlled study

AU - Hanifin, Jon

AU - Ellis, Charles N.

AU - Frieden, Ilona J.

AU - Fölster-Holst, Regina

AU - Stein Gold, Linda F.

AU - Secci, Angelo

AU - Smith, Angela J.

AU - Zhao, Cathy

AU - Kornyeyeva, Elena

AU - Eichenfield, Lawrence F.

PY - 2016

Y1 - 2016

N2 - Background: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. Objectives: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. Methods: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks. Results: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. Limitations: Further confirmatory phase-III studies are required. Conclusion: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.

AB - Background: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. Objectives: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. Methods: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks. Results: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. Limitations: Further confirmatory phase-III studies are required. Conclusion: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.

KW - Atopic dermatitis

KW - Atopic eczema

KW - OPA-15406

KW - Phosphodiesterase type 4 inhibitor

KW - Topical agents

KW - Topical calcineurin inhibitor

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