Objective: Primary objective: To determine pharmacokinetic profiles of an esketamine oral thin film with 50 or 100 mg esketamine; Secondary objective: (1) To determine the pharmacodynamic profile of an esketamine oral thin film containing 50 or 100…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
pijnbehandeling
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Plasma concentrations eskatemine and esnorketamine;
-Antinociceptive responses to pressure pain, electrical pain and heat pain.
Secondary outcome
Response to Bowdle and Bond & Lader questionnaires.
Background summary
The N-methyl-D-aspartate receptor antagonist ketamine is a potent anesthetic,
analgesic and antidepressant, increasingly used at subanesthetic doses to treat
different forms of pain, as well as depression. Currently the intravenous route
is the predominant form of ketamine delivery with inherent need for a
successful, sterile venipuncture by skilled healthcare personnel. This prevents
the use of ketamine in the out-hospital setting, particularly in case of acute
pain treatment (e.g., breakthrough pain). In the current study we will perform
a pharmacokinetic-pharmacodynamic study on the efficacy of an esketamine oral
thin film (OTF) in 20 healthy volunteers at a dose of 50 and 100 mg using a
cross-over design. We will obtain the following end-points: arterial plasma
concentrations of S-ketamine and S-norketamine, antinociceptive responses to
pressure pain, electrical pain and heat pain, psychomimetic side effects
(measured by the Bowdle and Bond & Lader questionnaires). Additionally, the get
an indication of the bioavailability of the esketamine OTF, we will infuse a
low dose esketamine via the intravenous route and measure plasma S-ketamine and
S-norketamine concentrations at the end of each experimental session. We
hypothesize that esketamine in OTF formulation will produce plasma S-ketamine
and S-norketamine concentrations that are associated with antinociception.
Study objective
Objective: Primary objective: To determine pharmacokinetic profiles of an
esketamine oral thin film with 50 or 100 mg esketamine; Secondary objective:
(1) To determine the pharmacodynamic profile of an esketamine oral thin film
containing 50 or 100 mg esketamine with endpoints antinociception and
psychomimetic side effects; (2) To determine safety and tolerability of the
esketamine oral thin film.
Study design
This study has an exploratory, open-label, crossover and randomized design.
Intervention
Administration of S-ketamine mucosal patch (50 mg and 100 mg)
Study burden and risks
In this open label study, we will assess the pharmacokinetic profile of two
doses of an esketamine oral thin film in healthy volunteers. We expect few if
any adverse effect but will gain valuable data on the plasma concentration
effect profile of this novel form of esketamine administration. Such a
formulation will be suitable for treatment of acute and chronic (breakthrough)
pain. As such we believe this to be a valid study with a positive risk benefit
balance.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- aged 18-45 years,
- body mass index > 19 and < 30 kg/m2,
- able to understand the written informed consent form,
- able to communicate with the staff,
- able and willing to complete the study procedures,
- signed the informed consent form,
- deemed suitable by the investigators.
- nonsmoking for the last 3 months.
Exclusion criteria
- Presence or history of any medical or psychiatric disease (incl. a history of
substance abuse, anxiety, or the presence of a painful syndrome);
- Use of any medication in the three months prior to the study (incl.
paracetamol or other pain killers);
- Use of more than 21 alcohol units per week;
- Use of illegal substances, including cannabis, in the 4 weeks prior to the
study;
- A positive urinary drug test or a breath alcohol test at screening or on the
morning of the experiment;
- Pregnancy, lactating or a positive pregnancy test on the morning of the
experiment;
- Participation in another drug trial in the 60 days prior to dosing.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005185-33-NL |
| CCMO | NL75727.058.20 |