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A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch

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Abstract

Rationale

Monoamine oxidase B (MAO-B) activity is reduced in smokers. A MAO-B inhibitor alone or co-administered with nicotine may mimic the effects of smoking and be a candidate drug for smoking cessation.

Objective

This study aims to determine the efficacy and safety of EVT302, a selective reversible MAO-B inhibitor, alone and on top of nicotine patch (NP) in smoking cessation.

Methods

This was a randomised, double blind, placebo-controlled phase II, multicentre trial. Smokers (≥10 cigarettes/day) received either EVT302 (N = 145) or placebo (N = 145), or EVT302 (N = 61) or placebo (N = 61) on top of open label NP 21 mg/day for 8 weeks. The main comparison was between EVT302 and placebo without NP. The primary outcome measure was end-of-treatment 4-week continuous abstinence rate (CAR). Secondary outcome measures: point prevalence abstinence rate, saliva cotinine concentrations in the groups without NP, urge to smoke, nicotine withdrawal symptoms and assessment of subjective effects of cigarettes.

Results

The 4-week CAR was 15.2 % in the placebo, 17.2 % in the EVT302, 26.8 % in the NP + placebo and 32.8 % in the NP + EVT302 groups, respectively. There was no difference between EVT302 and placebo either alone (adjusted OR: 1.45, 95 % CI: 0.65–3.26) or when co-administered with NP. No statistically significant difference occurred for the secondary outcome measures.

Conclusions

The selective, reversible MAO-B inhibitor EVT302 was not superior to placebo in helping smokers quit, in line with data with selegiline and confirms that MAO-B inhibitors are not effective in smoking cessation. Co-administration of NP does not provide a supplementary benefit.

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Acknowledgments

This study was funded by Evotec NeuroSciences GmbH.

Conflicts of interest

Ivan Berlin has received consultancy payments and travel funding from Pfizer Ltd and Sanofi Aventis in the last 5 years. He received a consultancy payment from Evotec Ltd for preparing the current study’s research protocol. Ian M. Hunneyball, Doris Greiling, Stephen Jones and Hermann Fuder were employees of Evotec. Hans-Detlev Stahl is an employee of ClinPharm International GmbH Prufzentrum Leipzig.

Author information

Authors and Affiliations

  1. Département de Pharmacologie, Hôpital Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris-Faculté de médicine, Université P. & M. Curie-INSERM U894, 47, bd de l’Hôpital, 75013, Paris, France

    Ivan Berlin

  2. Evotec (UK) Ltd, 114 Milton Park, Abingdon, Oxfordshire, OX14 4SA, UK

    Ian M. Hunneyball & Stephen P. Jones

  3. Evotec AG, Schnackenburgallee 114, 22525, Hamburg, Germany

    Doris Greiling & Hermann Fuder

  4. ClinPharm International GmbH Prufzentrum Leipzig, Johannisplatz 1, 04103, Leipzig, Germany

    Hans-Detlev Stahl

Authors
  1. Ivan Berlin
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  2. Ian M. Hunneyball
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  3. Doris Greiling
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  4. Stephen P. Jones
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  5. Hermann Fuder
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  6. Hans-Detlev Stahl
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Corresponding author

Correspondence to Ivan Berlin.

Additional information

Hermann Fuder is deceased.

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Berlin, I., Hunneyball, I.M., Greiling, D. et al. A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch. Psychopharmacology 223, 89–98 (2012). https://doi.org/10.1007/s00213-012-2692-2

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  • DOI: https://doi.org/10.1007/s00213-012-2692-2

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