A single‐dose, randomized, double‐blind, double dummy, placebo and positive‐controlled, five‐way cross‐over study to assess the pharmacodynamic effects of lorediplon in a phase advance model of insomnia in healthy Caucasian adult male subjects

Horoszok, Lucy; Baleeiro, Thais; D’Aniello, Fabiana; Gropper, Savion; Santos, Benjamín; Guglietta, Antonio; Roth, Thomas

doi:10.1002/hup.2395

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…Following single-dose administration, a dose-related awakening effect was observed, consistent with the pharmacology of H 3 R antagonists (Horoszok et al, 2014; Krystal et al, 2011; Mehta et al, 2001; Mehta et al, 2004). The sensitivity of WASO, however, appeared to decrease approximately 10-fold after multiple dosing.…”

Section: Discussionsupporting

confidence: 71%

Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects

et al. 2016

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CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement. Two randomized, double-blind, placebo-controlled dose escalation studies with single (0.02 to 5 mg) or multiple administration (0.02 to 0.5 mg once daily) of CEP-26401 were conducted in healthy subjects. Plasma and urine samples were collected to investigate CEP-26401 pharmacokinetics. Pharmacodynamic endpoints included a subset of tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and nocturnal polysomnography. Population pharmacokinetic-pharmacodynamic modeling was conducted on one CANTAB and one polysomnography parameter of interest. CEP-26401 was slowly absorbed (median tmax range 3-6 hours) and the mean terminal elimination half-life ranged from 24-60 hours. Steady-state plasma concentrations were achieved within six days of dosing. CEP-26401 exhibits dose- and time-independent pharmacokinetics, and renal excretion is a major elimination pathway. CEP-26401 had a dose-dependent negative effect on sleep, with some positive effects on certain CANTAB cognitive parameters seen at lower concentrations. The derived three compartment population pharmacokinetic model, with first-order absorption and elimination, accurately described the available pharmacokinetic data. CEP-26401 was generally well tolerated up to 0.5 mg/day with most common treatment related adverse events being headache and insomnia. Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement.

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Section: Discussionsupporting

confidence: 71%

Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects

et al. 2016

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“…143 Lorediplon A phase I study of the pharmacodynamics of lorediplon showed that it decreased WASO and increased total sleep time. 144 In a comparison with both placebo and zolpidem, lorediplon showed similar results to zolpidem. A randomized, phase II double blind, placebo controlled crossover study to evaluate the dosage needed and the drug's efficacy in sleep maintenance and sleep onset as well as its adverse effect profile began in 2014.…”

Section: Skp-1041mentioning

confidence: 87%

Advances in the management of chronic insomnia

Kay-Stacey

Attarian

2016

BMJ

116

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Chronic insomnia is a common condition that affects people worldwide and has negative effects on patients' health and wellbeing. The treatment of insomnia can be complex and time consuming for patients and providers. Although behavioral interventions are the first line therapy, there are barriers to access for these treatments. However, in recent years, alternative ways of providing these behavioral therapies that make them more widely available have been investigated. Drugs also play an important role in the treatment of insomnia and new drugs have been introduced as options for treating patients with sleep initiation and sleep maintenance insomnia. In this review, we will discuss advances in the past six years in both non-pharmacologic and pharmacologic treatments for patients with chronic insomnia. We will also review the controversies surrounding some of the current drug treatments, as well as the role that technology and personal activity monitoring devices may play in treating insomnia.

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“…1 Particularly, some synthetic purine analogues containing pyrazolo [1,5-a]pyrimidine nucleus have received augmented interest in recent years due to their broad range of applications in medicinal chemistry and drug design. 2 For instance, the anxiolytic agent ocinaplon, 3 and the hypnotic drugs indiplon, 4 lorediplon, 5 and zaleplon, 6 among others potential drugs 7 have this structural motif of pyrazolo [1,5-a]pyrimidine (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Simple access toward 3-halo- and 3-nitro-pyrazolo[1,5-a]pyrimidines through a one-pot sequence

2017

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A single‐dose, randomized, double‐blind, double dummy, placebo and positive‐controlled, five‐way cross‐over study to assess the pharmacodynamic effects of lorediplon in a phase advance model of insomnia in healthy Caucasian adult male subjects

Cited by 15 publications

References 17 publications

Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects

Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects

Advances in the management of chronic insomnia

Simple access toward 3-halo- and 3-nitro-pyrazolo[1,5-a]pyrimidines through a one-pot sequence

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