To evaluate the relative oral bioavailability and dose proportionality of concept formulations compared with the reference formulation of aticaprant when administered in healthy adult participants. This part will be conducted by PRA.To evaluate the…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics
Secondary outcome
Pharmacogenomics
Biomarkers
Safety
Background summary
Aticaprant is a small molecule, high affinity, selective kappa opioid receptor
(KOR) antagonist, with potential efficacy for the treatment of mood disorders.
This study is designed to examine the PKs of aticaprant concept formulations,
in comparison with aticaprant reference formulations. This information may be
used to support future clinical studies.
Study objective
To evaluate the relative oral bioavailability and dose proportionality of
concept formulations compared with the reference formulation of aticaprant when
administered in healthy adult participants. This part will be conducted by PRA.
To evaluate the PK of aticaprant in CSF after single oral dose administration
of aticaprant in healthy adult participants between 55 and 75 years of age.
This part will be conducted by CHDR.
Study design
The study will be conducted in 4 parts in healthy adult participants.
Part 1 will consist of Subpart 1A and Subpart 1B consisting of a total of 4
periods. Subpart 1A is a randomized, open label, 3-way crossover, 3-period
study to evaluate the relative bioavailability of a single dose of aticaprant
administered as Formulation Concept 1 compared to the same dose of aticaprant
administered as reference formulation and to evaluate dose proportionality of
another single dose of aticaprant administered as Formulation Concept 1.
Subpart 1B consists of a fourth period to evaluate the food effect of a single
dose of aticaprant administered as Formulation Concept 1.
The design of part 2 is the same as part 1, but with a different Formulation
Concept (Formulation Concept 2).
Based on the need of a formulation development plan, Part 3 may or may not be
conducted. Part 3, if conducted, will consist of an open label, 3-period,
single-dose, 3-way crossover design to evaluate the relative bioavailability
and/or food effect related to different oral formulations of aticaprant.
Part 4 will consist of an open-label, single-period, single-dose study in
healthy elderly male and female participants which involves continuous CSF
sampling.
Intervention
Aticaprant as reference formulation and concept formulations.
Study burden and risks
The safety and tolerability data so far accumulated for aticaprant in both
healthy participants and participants with mood disorders were generally
acceptable based on a thorough review of the safety information from completed
and ongoing clinical studies. The principal mitigations for potential risks
include the maintenance of an appropriate safety margin based on nonclinical
study drug exposure, appropriate selection of the trial population,
prespecified safety monitoring procedures, and the selection of the trial
facility, where close monitoring can be performed and rapid institution of
appropriate care can be given. The potential risks can be monitored clinically
and/or with laboratory tests and have been considered when determining the
stopping rules for this clinical trial.
In addition to the potential risks associated with study drug administration,
there is minimal risk associated with trial procedures including scheduled,
periodic venipuncture (limited to < 500 mL) and non-invasive procedures
including vital sign assessments, SARS-CoV-2 test and ECGs. Subjects are
exposed to risks associated with the insertion, indwelling an removal of a
spinal catheter in Part 4. To lower these risks, a population of older subjects
was chosen, the catheter will be inserted by a trained physician and close
monitoring will be performed in the trial facility. Overall, the benefit-risk
profile is considered appropriate for this trial.
Turnhoutseweg 30
Beerse B-2340
BE
Turnhoutseweg 30
Beerse B-2340
BE
Listed location countries
Age
Inclusion criteria
All parts:
- Healthy based on physical examination, medical history, clinical laboratory
tests, vital signs, and 12-lead ECG.
- Body mass index between 18 and 29.9 kg/m2 (inclusive), and body weight not
less than 50 kg.
- Female subjects should not be pregnant, and either not of childbearing
potential or practicing a highly effective method of contraception (see
clinical protocol for details).
- Blood pressure between 90 mmHg and 140 mmHg systolic, inclusive, and no
higher than 90 mmHg diastolic.
Part 1, 2 and 3:
- Healthy male and female participants between 18 and 55 years of age, inclusive
Part 4:
- Healthy male and female participants between 55 and 75 years of age,
inclusive.
See clinical protocol paragraph 5.1 for all inclusion criteria.
Exclusion criteria
- History of or current significant medical illness that the Investigator
considers should exclude the participant or that could interfere with the
interpretation of the study results.
- History of malignancy within 5 years before screening (exceptions are
squamous and basal cell carcinomas of the skin and carcinoma in situ of the
cervix, or malignancy, which is considered cured with minimal risk of
recurrence).
- Any known and relevant allergies, hypersensitivity, or intolerances.
- Presence of left bundle branch block, atrioventricular block (second degree
or higher), or a permanent pacemaker or implantable cardioverter defibrillator.
- Clinically-relevant gastrointestinal complaints per clinical judgment or
history of documented gastric disease.
- Current or past homicidal ideation/intent within the last 6 months, per the
investigator*s clinical judgment, or has current or past suicidal ideation with
some intent to act within 6 months prior to the start of the screening phase,
per the investigator*s clinical judgment or based on the Columbia Suicide
Severity Rating Scale (C-SSRS).
- Serology positive for hepatitis B surface antigen, hepatitis C virus
antibodies or human immunodeficiency virus antibodies at screening.
- Use of any prescription or nonprescription medication, except for
paracetamol/acetaminophen, hormone-based contraceptives and hormonal
replacement therapy within 14 days before the first dose of the study
intervention.
- Received an investigational intervention or used an invasive investigational
medical device within at least 1 month, before the planned first dose of study
intervention or is currently enrolled in an investigational study.
- Pregnant, or breast-feeding, or planning to become pregnant while enrolled in
this study or within 90 days after the last dose of study intervention.
- Plans to father a child while enrolled in this study or within 90 days after
the last dose of study intervention.
- Had major surgery within 12 weeks before screening, or will not have fully
recovered from surgery, or has surgery planned during the time the participant
is expected to participate in the study.
- History of substance or alcohol use disorder within 6 months before Screening
or positive alcohol and drug screening test.
- Employee of the investigator or study site, with direct involvement in the
proposed study or other studies under the direction of that investigator or
study site, as well as family members of the employees or the investigator.
- Donated blood or blood products or plasma or had substantial loss of blood
(more than 500 mL) within 3 months before the first administration of study
intervention in each part of the study or intention to donate blood or blood
products during the study.
- History of smoking or use of nicotine-containing substances within the
previous 3 months prior to screening.
- Drinks, on average, more than 8 cups of tea/coffee/cocoa/cola or other
caffeinated beverages per day.
See section 5.2 of the protocol for all exclusion criteria, including extra
exclusion criteria for part 4 of the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003048-25-NL |
| CCMO | NL78332.056.21 |