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Effects of Ethanol on the Pharmacokinetics of Extended-Release Oxycodone with Sequestered Naltrexone (ALO-02)

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Abstract

Background and Objectives

ALO-02 capsules, intended to deter abuse, contain pellets of extended-release oxycodone hydrochloride (HCl), an opioid agonist, surrounding sequestered naltrexone HCl, an opioid antagonist. The objective of this study was to determine the effects of administration of ALO-02 with 20 or 40 % ethanol on the pharmacokinetics of oxycodone.

Methods

This was an open-label, single-dose, randomized, three-way crossover study in 18 healthy fasting adults administered ALO-02 20/2.4 mg (oxycodone/naltrexone) with water, 20 % ethanol, or 40 % ethanol, each under naltrexone block.

Results

Median time to maximum concentration was 12 h postdose when ALO-02 was administered with water or 20 % ethanol and decreased to 8 h postdose with 40 % ethanol. Geometric mean area under the plasma concentration–time curve (AUC) from time zero extrapolated to infinity (AUC∞) and maximum concentration (C max) values were similar for ALO-02 administered with water or 20 % ethanol, and increased by about 13 and 37 %, respectively, for ALO-02 administered with 40 % ethanol versus water. The 90 % confidence intervals (CIs) for AUC∞ and C max ratios of ALO-02 with 20 % ethanol versus water were within 80–125 %; upper 90 % CIs were >125 % for ALO-02 with 40 % ethanol versus water. The most common adverse events were mild-to-moderate vomiting, nausea, headache, and somnolence. Incidence of adverse events increased for ALO-02 given with ethanol versus water.

Conclusions

Oxycodone exposures (C max) were unaffected when ALO-02 was administered with 20 % ethanol but C max increased by 37 % with 40 % ethanol versus water. ALO-02 administered with ethanol under naltrexone block was generally well tolerated.

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Acknowledgments

This study was sponsored by Pfizer Inc. All authors are employees of Pfizer Inc. Medical writing support was provided by Mary Kunjappu, PhD, of Engage Scientific Solutions and funded by Pfizer Inc.

Funding

Pfizer Inc.

Conflict of interest

All authors are employees of Pfizer Inc.

Ethical standards

This study was conducted according to principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects, Guidelines for Good Clinical Practice, and the Declaration of Helsinki. All participants provided informed consent prior to enrollment.

Author information

Authors and Affiliations

  1. Clinical Pharmacology, Pfizer Inc, 235 East 42nd Street, New York, NY, 10017, USA

    Bimal K. Malhotra

  2. Pfizer Inc, Collegeville, PA, USA

    Kyle Matschke

  3. Pfizer Inc, Groton, CT, USA

    Qiang Wang, Candace Bramson & Joanne Salageanu

Authors
  1. Bimal K. Malhotra
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  2. Kyle Matschke
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  3. Qiang Wang
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  4. Candace Bramson
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  5. Joanne Salageanu
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Corresponding author

Correspondence to Bimal K. Malhotra.

Additional information

Trial registration: ClinicalTrials.gov, identifier NCT01677039.

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Malhotra, B.K., Matschke, K., Wang, Q. et al. Effects of Ethanol on the Pharmacokinetics of Extended-Release Oxycodone with Sequestered Naltrexone (ALO-02). Clin Drug Investig 35, 267–274 (2015). https://doi.org/10.1007/s40261-015-0278-6

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  • DOI: https://doi.org/10.1007/s40261-015-0278-6

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