A methodology study to characterize 2-AG as a potential pharmacological biomarker in healthy human subjects for future clinical trials with a central MAGL inhibitor

Completed

Conditions: europsychiatrics disease in general in particular for affective disorders such as anxiety and depression
Neuropsychiatric diseases

Registration Number: NL-OMON50921

Lead Sponsor: Centre for Human Drug Research

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

- Healthy, male and female subjects between 25-65 of age, inclusive. For cohort
2: between 40 and 75 years of age, inclusive.
- Female participants must be postmenopausal or must be on hormonal
contraception for at least 6 months regulating the menstrual cycle.
- Subjects must have a BMI between > 18.0 and 30.0 kg/m2, inclusive
(BMI*<=*weight/height2).
- Subject must be healthy based on physical examination, medical history, vital
signs, and 12-lead Electrocardiogram (ECG). Minor abnormalities in ECG, which
are not considered to be of clinical significance by the investigator, are
acceptable.
- Subjects must be healthy based on clinical laboratory tests performed at
screening. If the results of the serum chemistry panel, hematology, or
urinalysis are outside the normal reference ranges, the subject may be included
only if the investigator judges the abnormalities to be not clinically
significant. This determination must be recorded in the subject's source
documents and initialed by the sub investigator.
- Subjects must be willing to adhere to the prohibitions and restrictions
specified in the protocol.
- Each subject must sign an informed consent form (ICF) indicating that he or
she understands the purpose and procedures required for the study and are
willing to participate in the study.
- Subjects must be willing to undergo intrathecal insertion of the spinal
catheter for 16 hours ±2.
- Agree to avoid any strenuous exercise from screening until the last day at
the clinical research unit.

Exclusion Criteria

- Pregnant woman.
- Past or present history of any clinically relevant psychiatric disorder as
classified according to DSM-IV or DSM 5, mood, anxiety and psychotic disorders
in particular.
- Subject has a history of drug or alcohol use disorder according to DSM-IV or
DSM 5 within 12 months before screening or has a positive test result(s) for
alcohol and/or drugs of abuse (including but not limited to: opiates (including
methadone), cocaine, amphetamines, methamphetamines, cannabinoids,
barbiturates, and benzodiazepines) at screening or admission to the clinical
unit.
- Significant coagulation abnormality (e.g. hemophilia, platelet counts less
than the lower limit of normal or clinically significant elevation in PT or PTT
at screening), or has a medical condition requiring treatment with an
anticoagulant (e.g. warfarin) or with two or more antiplatelet agents. Platelet
counts between 125,000 and 150,000/microliter are permissible as long as the
investigator confirms there is no evidence of current bleeding diathesis or
coagulopathy.
- Subject has abnormalities upon fundoscopy indicating an increased
Intracranial Pressure (ICP), unless assessed as safe by principal investigator
when no further evidence is present indicating ICP.
- History of clinically significant back pathology and/or back injury (e.g.
degenerative disease, spinal deformity, or spinal surgery) that may predispose
to complications or technical difficulty with the spinal catheter.*
- Subject smokes cigarettes (or equivalent) and/or has used nicotine-based
products within 3*months prior to spinal catheter insertion ; positive cotinine
test at screening and admission.
- Subject has a history of heparin allergy.
- Subject has undergone major lifestyle changes in the previous 6 months:
significant weight loss > 5kg or started a specific diet which could
potentially result in weight loss.
- Vulnerable subjects (e.g., a person kept in detention or a person under
guardianship).
- Subject is unable to read and understand the consent forms, complete
study-related procedures, and/or communicate with the study staff.
- Unsuitable veins for cannulation and/or repeated venepuncture.
- Diagnosis or suspicions of any sleep disorder in the last 6 months or current
complaints of sleep disturbance, irregular sleep schedule or shift work;
habitual daytime naps; travel across time zones in the last 4 weeks or daytime
symptoms attributable to unsatisfactory sleep.
- Use of a prescription medicine and or over-the-counter medicine influencing
the sleeping habits (such as benzodiazepines, melatonin) or occasional use
(last 6 months) of cannabis (in all its forms including the use of cannabidiol
(CBD)).