アルコール使用障害患者における非盲検単回投与試験

実験的：BPL-003 アーム

薬：BPL-003

単回鼻腔内投与

Percentage of Participants With Treatment Emergent Adverse Events

The number (%) of participants with at least one treatment-emergent adverse event is presented. More detailed information is provided in the dedicated 'Adverse Events' section

Percentage of Participants With Clinically Significant Abnormal Laboratory Tests

The number (%) of participants with any clinically significant abnormal laboratory tests (routine haematology, clinical chemistry and coagulation) is presented

Percentage of Participants With Clinically Significant Abnormal Vital Signs

The number (%) of participants with any clinically significant abnormal vital signs (blood pressure, heart rate and temperature) result is presented

Number of Participants With Post-baseline Suicidal Ideation or Behaviour Based on C-SSRS Score

The C-SSRS was performed at screening, on Day 0 (dosing day), and on Days 1, 7, and 84 post-dose. Participants were counted if they answered 'yes' to any question. At baseline, the C-SSRS assessed the worst-point suicidal ideation experienced during the participant's lifetime. Beyond baseline, suicidal ideation and behaviour since last visit was assessed.

Time to Readiness for Discharge Post-dose Using the Readiness for Discharge Questionnaire (RDQ)

The RDQ was a brief assessment scale to ensure that ahead of discharge after BPL-003 dosing, participants:

• Were fully responsive, aware of their surroundings, and reacted adequately
• The acute psychedelic effects of the drug had completely subsided
• Were fully orientated (name, location, time)
• Had normal (or only slightly elevated) blood pressure and pulse rate, and normal breathing frequency and body temperature
• Had a stable gate, normal muscle coordination, and could walk safely
• Had only mild to moderate potential side affects that did not need to be medically monitored
• Had no acute suicidal ideations or suicidal intentions
• Possible distress or feelings of overwhelm had sufficiently subsided and the participant felt safe to be discharged.

Readiness for discharge was assessed at 90 minutes post-dose and then every 30 minutes until the participant was deemed ready for discharge (eg, the answer was 'yes' to all of the above items).

Percentage of Participants With Occurrence of Reactivation Using the Reactivation Questionnaire (ReAQ)

The occurrence and (if applicable) frequency, emotional valence, and functional impact of any reactivation events was determined. To determine if reactivation had occurred, participants were asked if they had any flashbacks or recurrence of any effects of the study drug experience.

Effects on the Mystical Experience Questionnaire (MEQ-30)

The MEQ-30 was performed to assess the extent of a participant's mystical experience after receiving BPL-003 on Day 0 (dosing day). The questionnaire comprises a list of 30 phenomena, with subscales to measure mystical, positive mood, transcendence of space and time, and ineffability factors, measured on a 0 to 5 scale (0=none; not at all to 5=extreme). A 'total MEQ-30 score' was calculated for each participant as the average of all their responses. The total MEQ-30 score is presented. The higher the score, the greater the mystical experience. A total score of ≥3 was considered to be a significant mystical experience.

Effects on the Ego Dissolution Inventory (EDI)

The EDI was performed to assess the extent of a participant's dissolution of ego after receiving BPL-003 on Day 0 (dosing day). The inventory comprises 8 statements. Participants rated their agreement to each statement by marking on a visual analogue scale from 0 ("no, not more than usually") to 100 ("yes, entirely or completely"). Higher scores are indicative of more intense ego dissolution. In practice, this means participants with higher scores could have a reduced sense of having a distinct, separate self; greater feelings of unity with the environment or universe; a loss of self-referential thoughts or identity; or altered boundaries between 'self' and 'other'. A 'total EDI score' was calculated for each participant as the average of their individual-item scores. The total EDI score is presented.

Percentage of Participants With a Complete Mystical Experience Using the MEQ-30

The MEQ-30 was performed to assess the extent of a participant's mystical experience after receiving BPL-003 on Day 0 (dosing day). The questionnaire comprises a list of 30 phenomena, with subscales to measure mystical, positive mood, transcendence, and ineffability factors, measured on a 0 to 5 scale (0=none; not at all to 5=extreme). A 'total MEQ-30 score' was calculated for each participant as the average of all their responses.

A complete mystical experience was defined as reaching or exceeding a score of 3 on all four sub-domains (mystical, positive mood, transcendence of time and space, and ineffability) of the MEQ-30 scale.

Percentage of Participants Experiencing an Ego Dissolution Using the EDI

The EDI was performed to assess the extent of a participant's dissolution of ego after receiving BPL-003 on Day 0 (dosing day). The inventory comprises 8 statements. Participants rated their agreement to each statement by marking on a visual analogue scale from 0 ("no, not more than usually") to 100 ("yes, entirely or completely"). Participants were classed as experiencing an ego dissolution if they had a total score of >50.0 out of 100 on the EDI scale.

Description of the BPL-003 Subjective Experience Data, From a Qualitative Interview

After BPL-003 dosing, participants had the option to participate in a one-to-one guided interview with independent researchers trained in microphenomenology methods to describe their psychedelic experience. Temporal aspects of drug effects (e.g., sensory, cognitive, metacognitive, and sense of self/other/connectedness) were elicited through open-ended interview questions.

Feedback From Therapists on the Frequency and Duration of Psychotherapy Sessions, Therapy Manual and Overall Therapy Model

Key themes from qualitative feedback on the treatment model was sought from therapists on frequency and duration of psychotherapy sessions, implementation of therapy manual, and overall therapy model. Feedback was obtained in a qualitative interview with each therapist after each participant's last integration session (between Day 15 and Day 42).

Semi-structured Interview to Assess Psychological Changes Following BPL-003 Treatment

After BPL-003 dosing, participants had the option to participate in a semi-structured interview. The interviews were topic-guided, qualitative interviews to understand psychological changes shortly after dosing on Day 1, and on Day 84.

Timeline Follow-Back (TLFB) Interview to Assess the Percentage of Abstinent Days (PAD)

Using the TLFB interview, the PAD in the 85 days before Day -3 (or start of detox) vs the PAD post-dosing measured on Days 14, 28, 56, and 84 were determined to assess alcohol use.

TLFB Interview to Assess the Percentage of Heavy Drinking Days (PHDD)

Using the TLFB interview, the PHDD in the 85 days before Day -3 (or start of detox) vs PHDD post-dosing measured on Days 14, 28, 56, and 84 were determined to assess alcohol use.

TLFB Interview to Assess the Percentage of Drinking Days (PDD)

Using the TLFB interview, the PDD in the 85 days before Day -3 (or start of detox) vs PDD post-dosing measured on Days 14, 28, 56, and 84 were determined to assess alcohol use.