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Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy.
Sleep. 2020 Apr 15; 43(4)S

Abstract

OBJECTIVES

To evaluate the human abuse potential of pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist recently approved by the US Food and Drug Administration for the treatment of excessive daytime sleepiness in adult patients with narcolepsy.

METHODS

Nondependent, recreational stimulant users able to distinguish phentermine HCl 60 mg from placebo in a drug discrimination test were randomized in a four-period, double-blind, crossover design to receive single doses of pitolisant 35.6 mg (therapeutic dose), pitolisant 213.6 mg (supratherapeutic dose), phentermine HCl 60 mg, and placebo. The primary endpoint was maximum effect (Emax) on the 100-point Drug Liking ("at this moment") visual analog scale.

RESULTS

In 38 study completers (73.7% male; 65.8% white; mean age, 33.3 years), mean Drug Liking Emax was significantly greater for phentermine versus pitolisant 35.6 mg (mean difference, 21.4; p < 0.0001) and pitolisant 213.6 mg (mean difference, 19.7; p < 0.0001). Drug Liking Emax was similar for pitolisant (both doses) and placebo. Similarly, for key secondary measures of Overall Drug Liking and willingness to Take Drug Again, mean Emax scores were significantly greater for phentermine versus pitolisant (both doses) and similar for pitolisant (both doses) versus placebo. The incidence of adverse events was 82.1% after phentermine HCl 60 mg, 72.5% after pitolisant 213.6 mg, 47.5% after pitolisant 35.6 mg, and 48.8% after placebo administration.

CONCLUSIONS

In this study, pitolisant demonstrated significantly lower potential for abuse compared with phentermine and an overall profile similar to placebo; this suggests a low risk of abuse for pitolisant.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov NCT03152123. Determination of the abuse potential of pitolisant in healthy, nondependent recreational stimulant users. https://clinicaltrials.gov/ct2/show/NCT03152123.

Authors+Show Affiliations

Syneos Health, Raleigh, NC. Department of Toxicology and Pharmacology, University of Toronto, Toronto, ON, Canada.Syneos Health, Toronto, ON, Canada.Syneos Health, Toronto, ON, Canada.Bioprojet Pharma, Paris, France.Bioprojet Biotech, Saint Grégoire, France.Harmony Biosciences LLC, Plymouth Meeting, PA.Bioprojet Pharma, Paris, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31626696

Citation

Setnik, Beatrice, et al. "Evaluation of the Abuse Potential of Pitolisant, a Selective H3-receptor Antagonist/inverse Agonist, for the Treatment of Adult Patients With Narcolepsy With or Without Cataplexy." Sleep, vol. 43, no. 4, 2020.
Setnik B, McDonnell M, Mills C, et al. Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy. Sleep. 2020;43(4).
Setnik, B., McDonnell, M., Mills, C., Scart-Grès, C., Robert, P., Dayno, J. M., & Schwartz, J. C. (2020). Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy. Sleep, 43(4). https://doi.org/10.1093/sleep/zsz252
Setnik B, et al. Evaluation of the Abuse Potential of Pitolisant, a Selective H3-receptor Antagonist/inverse Agonist, for the Treatment of Adult Patients With Narcolepsy With or Without Cataplexy. Sleep. 2020 Apr 15;43(4) PubMed PMID: 31626696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy. AU - Setnik,Beatrice, AU - McDonnell,Michael, AU - Mills,Catherine, AU - Scart-Grès,Catherine, AU - Robert,Philippe, AU - Dayno,Jeffrey M, AU - Schwartz,Jean-Charles, PY - 2019/04/30/received PY - 2019/09/06/revised PY - 2019/10/19/pubmed PY - 2019/10/19/medline PY - 2019/10/19/entrez KW - drug abuse KW - narcolepsy KW - pitolisant JF - Sleep JO - Sleep VL - 43 IS - 4 N2 - OBJECTIVES: To evaluate the human abuse potential of pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist recently approved by the US Food and Drug Administration for the treatment of excessive daytime sleepiness in adult patients with narcolepsy. METHODS: Nondependent, recreational stimulant users able to distinguish phentermine HCl 60 mg from placebo in a drug discrimination test were randomized in a four-period, double-blind, crossover design to receive single doses of pitolisant 35.6 mg (therapeutic dose), pitolisant 213.6 mg (supratherapeutic dose), phentermine HCl 60 mg, and placebo. The primary endpoint was maximum effect (Emax) on the 100-point Drug Liking ("at this moment") visual analog scale. RESULTS: In 38 study completers (73.7% male; 65.8% white; mean age, 33.3 years), mean Drug Liking Emax was significantly greater for phentermine versus pitolisant 35.6 mg (mean difference, 21.4; p < 0.0001) and pitolisant 213.6 mg (mean difference, 19.7; p < 0.0001). Drug Liking Emax was similar for pitolisant (both doses) and placebo. Similarly, for key secondary measures of Overall Drug Liking and willingness to Take Drug Again, mean Emax scores were significantly greater for phentermine versus pitolisant (both doses) and similar for pitolisant (both doses) versus placebo. The incidence of adverse events was 82.1% after phentermine HCl 60 mg, 72.5% after pitolisant 213.6 mg, 47.5% after pitolisant 35.6 mg, and 48.8% after placebo administration. CONCLUSIONS: In this study, pitolisant demonstrated significantly lower potential for abuse compared with phentermine and an overall profile similar to placebo; this suggests a low risk of abuse for pitolisant. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03152123. Determination of the abuse potential of pitolisant in healthy, nondependent recreational stimulant users. https://clinicaltrials.gov/ct2/show/NCT03152123. SN - 1550-9109 UR - https://www.unboundmedicine.com/medline/citation/31626696/Evaluation_of_the_abuse_potential_of_pitolisant,_a_selective_H3-receptor_antagonist/inverse_agonist,_for_the_treatment_of_adult_patients_with_narcolepsy_with_or_without_cataplexy L2 - https://academic.oup.com/sleep/article-lookup/doi/10.1093/sleep/zsz252 DB - PRIME DP - Unbound Medicine ER -
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