A Phase 2a, Placebo-Controlled Randomized, Double-Blind Trial to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Psilocybin Oral Solution in Adults With Generalized Anxiety Disorder
This Phase 2a clinical trial is designed to evaluate the safety, tolerability, and preliminary efficacy of a 3 mg dose of psilocybin oral solution for the treatment of Generalized Anxiety Disorder (GAD). The study consists of three sequential phases: Screening Phase (up to 4 weeks), Open-label Run-in Phase (4 weeks), Double-blind Treatment Phase (4 weeks) Screening Phase During the Screening Visit, participants will provide informed consent and undergo a comprehensive medical evaluation, including an abbreviated psychiatric assessment, to determine eligibility. To qualify, patients must have a clinician-rated Hamilton Anxiety Rating Scale (HAM-A) score ≥14. Additionally, participants must not be on regular anxiolytic treatment or must have discontinued such treatment at least 4 weeks prior to the start of the Open-label Run-in Phase. Open-label Run-in Phase Eligible patients will proceed to the 4-week Open-label Run-in Phase. During this phase, patients will attend four weekly clinic visits, supplemented by weekly remote contacts (via phone or email). At different timepoints during the OL Run-in Phase, participants will complete safety assessments, undergo cognitive testing and EEG and other patient reported outcomes (PROs). Double-blind Treatment Phase Participants who demonstrate a treatment response during the Open-label Phase-defined as a ≥50% reduction in GAD-7 score from baseline-will be randomized 1:1 to receive either psilocybin oral solution or placebo at the Double-blind Baseline Visit. Patients not meeting the response criteria will undergo End-of-Treatment (ET) procedures at this visit. At different timepoints during the DB Treatment Phase, participants will complete safety assessments, undergo cognitive testing and EEG and other patient reported outcomes (PROs). Completion of the End of Treatment (ET) phase will be 2 weeks to further assess safety and PROs.
• Must provide written informed consent prior to the initiation of any protocol-specific procedures.
• Male and female adults, between 18 and 60 years of age, inclusive.
• Meets DSM-V criteria for a primary diagnosis of GAD at Screening (duration of diagnosis ≥1 year, based on self-report), confirmed using the MINI.
• Clinician-rated GAD-7 score ≥14 at Screening (Visit 1).
• Clinician-rated HAM-A score ≥14 at Screening (Visit1).
• Females must be non-pregnant and non-lactating and must fulfil at least one of the following:
‣ Be surgically sterile for a minimum of 6 months (achieved through hysterectomy, oophorectomy, or bilateral salpingectomy; note that tubal ligation is not considered a method of permanent sterilization).
⁃ Post-menopausal for a minimum of 1 year (confirmed by follicle-stimulating hormone test).
⁃ Agree to avoid pregnancy and use a medically acceptable method of contraception with male sexual partners from at least 30 days prior to the study until 30 days after the study has ended (last study procedure).
⁃ Medically acceptable methods of contraception include any of the following:
⁃ Double-barrier methods (e.g., male condom, spermicide with diaphragm or spermicide with cervical cap)
⁃ Oral contraceptives; hormonal patch, implant or injection; or hormonal or non-hormonal intrauterine device. The male partner should use, at all times, a male condom with spermicide, should the female Patient choose to use any of these methods
⁃ Complete abstinence, should it be in line with the Patient's preferred and usual lifestyle.
• Males who are able to father children must agree to use medically acceptable methods of contraception during the study and for 30 days after the last study drug administration. If a patient's partner should become pregnant during his participation in the study and for 30 days after he has completed his last study drug administration, the patient must inform study staff immediately. Medically acceptable methods of contraception include:
‣ Using a condom with a female partner of child-bearing potential who is using oral contraceptives; hormonal patch, implant or injection; hormonal or non-hormonal intrauterine device; or diaphragm or cervical cap with spermicide
⁃ Complete abstinence, should it be in line with the patient's preferred and usual lifestyle.
• Males must refrain from sperm donation from clinic admission to at least 30 days after the last dose of study drug.
• Must be able to speak, read, and understand English sufficiently to allow completion of all study assessments.
⁃ Must be willing to comply with the requirements and restrictions of the study.