| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Not possible to specify |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • To investigate the inhibition of primary CNS effects of a THC challenge by CB1 receptor antagonist compared to placebo in healthy occasional users of cannabis |
|
| E.2.2 | Secondary objectives of the trial |
• To investigate the inhibition of secondary CNS effects of a THC challenge by CB1 receptor antagonist compared to placebo in healthy occasional users of cannabis
• To evaluate the pharmacokinetics of ANEB-001, THC, 11-OH-THC and 11-nor-9 carboxy-THC in plasma
• To evaluate the pharmacokinetics of ANEB-001 and potential metabolites in urine (Part B cohort 3 to 6 and Part C only)
• To assess safety and tolerability of ANEB-001 in healthy occasional users of cannabis
Part C only:
• To evaluate the CNS effects of a high-dose THC challenge administered simultaneously with the CB1 receptor antagonist ANEB-001 relative to baseline in healthy occasional users of cannabis. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study-mandated procedure
2. Healthy male or female subjects, 18 to 45 years of age, inclusive at screening.
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg.
4. All women of child bearing potential and all males must practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment.
5. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.
6. Occasional cannabis users with
a. Lifetime cannabis use on at least 10 occasions.
b. In the past 6 months, the mean cannabis use should not exceed one occasion per week.
c. Subjects should be able to refrain from using cannabinoids at least 3 weeks prior to dosing up to the end of the study.
d. Urine drug screen must be negative prior to dosing.
|
|
| E.4 | Principal exclusion criteria |
8. Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to first dosing of this study).
9. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent other than recreative use of THC
10. Positive test for drugs of abuse (other than THC) at screening.
11. Positive test for drugs of abuse pre-dose.
17. If a woman:, pregnant, or breast-feeding, or planning to become pregnant during the study.
19. Clinically significant suicidal ideation in the past 5 years as judged by the investigator or any life-time suicide attempts.
20. History of cannabis-induced psychosis, schizophrenia or other clinically relevant psychiatric disorders, as judged by the investigator.
21. History of a clinically significant mood disorder, including but not limited to major depressive disorder, as judged by the investigator. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Visual Analogue Scale (VAS) “Feeling High” according to modified Bowdle psychedelic scale (mm)
• VAS “Alertness” according to Bond and Lader (mm)
• Body sway: o antero-posterior sway (mm);
• Heart rate (bpm).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
for VAS and Body sway ; pre dose till 8 hrs post dose (hourly)
HR ; day -1 - FU (7-14 days after dosing) |
|
| E.5.2 | Secondary end point(s) |
CNS effects
• VAS Bond and Lader:
o mood (mm),
o calmness (mm).
• VAS Bowdle
o Internal perception
o External perception
•State-Trait Anxiety Inventory (STAI)
o State anxiety score
• Saccadic eye movements:
o saccadic reaction time (second),
o saccadic peak velocity (degrees/second), and
o saccadic inaccuracy (%);
• Smooth pursuit eye movements:
o percentage of time the eyes of the subjects are in smooth pursuit of the target (%);
• Adaptive tracking:
o average performance (%);
• Pupillometry (mm)
• N-Back
o Average reaction time for zero, one and two-back (ms)
o (nr correct – nr incorrect)/total for zero, one and two-back
Starting with cohort 3 of Part B:
• VAS “Any drug effect” (mm)
• VAS “Good drug effect” (mm)
• VAS “Bad drug effect” (mm)
PD outcomes starting in Part C:
State-Trait Anxiety Inventory, VAS ”Mood”, VAS “Calmness” (Bond&Lader), VAS “Internal perception”, VAS “External Perception” (Bowdle), VAS “Any drug effect”, VAS “Good drug effect” and VAS “Bad drug effect”, Symbol Digit Substitution Test (SDST), Visual Verbal Learning Test (VVLT), Alternate finger tapping (AFT), Timed Up and Go (TUG), Basic Symptom Inventory (BSI), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression of Severity (CGIS), exploratory accelerometer-based measurements
PK
PK parameters of ANEB-001, THC and 11-OH-THC by non-compartmental analysis of the plasma concentration-time data:
• AUCinf, AUClast, CL/F, Cmax, t1/2, tlag, tmax, Vz/F
• Dose-normalized PK parameters: AUCinf, AUClast, Cmax
• Urine PK parameters: Aelast, Aelast%, CLR
Safety and tolerability
• Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit
• Concomitant medication throughout the study at every study visit
• Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)), Respiratory Rate (pm), O2 Saturation (%)) as per assessment schedule
• Clinical laboratory tests (Hematology, blood chemistry and urinalysis) as per assessment schedule
• ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per assessment schedule
• VAS Nausea
• Suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
• Depressive symptoms as assessed by Beck Depression Inventory-II
• Dissociative symptoms as assessed by Clinician Assessed Dissociative States Scale (CADSS) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
CNS endpoints ; pre-dose till 8hr post dose
PK ; pre-dose - day 2
C-SSRS; day -1 - FU (7-14 days after dosing)
Safety endpoints ; day -1 - FU (7-14 days after dosing) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
Print
