Clinical TrialAnxiety DisordersPsilocybinPsilocybinPsilocybinNot yet recruiting

A Phase 2b double-blind, randomized, low-dose comparator-controlled clinical trial to assess the efficacy and safety of PEX010 in psilocybin-assisted psychotherapy for the treatment of adjustment disorder due to incurable cancer diagnosis

Double-blind, randomized 1:1:1 Phase 2b dose-comparison trial (n=84) comparing single oral 25 mg, 10 mg and 1 mg PEX010 plus psychotherapy for adjustment disorder due to an incurable cancer diagnosis.

Target Enrollment
84 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

This interventional, double-blind randomized trial compares three doses of oral PEX010 (25 mg, 10 mg, 1 mg) administered as a single supervised dosing session (Day 14) paired with preparatory and integration psychotherapy in participants with adjustment disorder following an incurable cancer diagnosis.

Participants complete three preparatory therapy sessions in the two weeks prior to dosing (two may be remote), an ~8-hour supervised drug session with therapist support and mouth checks, and integration sessions on Day 15 and Day 21, with follow-up visits through Day 253; non-responders at Week 12 may be offered a second PAP cycle (max 2).

Primary outcome is change in anxiety severity measured by HAM-A; key secondary and safety assessments include ADNM-20, S-STS, vitals, ECG and laboratory monitoring.

Study Protocol

Preparation

3 sessions
60 min each

Dosing

1 sessions
480 min each

Integration

2 sessions
60 min each

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

PEX010 25 mg

experimental

Single oral 25 mg PEX010 (capsule) administered Day 14 with therapist support during an ~8-hour session.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Capsule; mouth check prior to dosing; therapist present throughout session.

PEX010 10 mg

active comparator

Single oral 10 mg PEX010 (capsule) administered Day 14 with therapist support.

Interventions

  • Psilocybin10 mg
    via Oral• single dose• 1 doses total

PEX010 1 mg (low)

active comparator

Single oral 1 mg low-dose comparator PEX010 (capsule) administered Day 14 with therapist support.

Interventions

  • Psilocybin1 mg
    via Oral• single dose• 1 doses total

    Low-dose comparator

Participants

Ages
18 – 80
Sexes
Male & Female

Inclusion Criteria

  • To be eligible for study entry participants must satisfy all of the following criteria:
  • 1. Screening AjD diagnosis (ICD-11), as defined by an ADNM-20 score ≥47.5 and a Distress Thermometer score ≥4.
  • 2. Screening HAM-A Score ≥18 (moderate anxiety).
  • 3. Adults aged 18 to 80 years (inclusive) at screening.
  • 4. Diagnosed with incurable cancer and a minimum life-expectancy of 12 months in the opinion of the treating physician, with performance status of 0-2 on the ECOG scale.
  • 5. Agrees not to commence any new psychiatric medications or psychotherapies from Screening to Week 10.
  • 6. Able to communicate well and follow study procedures; sufficient English to build rapport with study staff.
  • 7. Judged to be of low suicide risk based on Sheehan-Suicide Tracking Scale (S-STS) and the opinion of a research team psychiatrist.
  • 8. Medically suitable as determined by interview, questionnaire, physical exam, ECG and blood tests.
  • 9. Have access to a compatible device for digital technology (smartphone/tablet).
  • 10. Agree not to take sedating medications for ≥12 hours before dosing (benzodiazepines, zopiclone, eszopiclone, zaleplon, zolpidem); cancer pain meds permitted.
  • 11. Willing and able to refrain from smoking during the dosing session; nicotine replacement may be permitted with medical monitor agreement.
  • 12. Agree to refrain for 1 week before dosing from illegal drugs, non-prescription meds (including cannabis/CBD/THC), nutritional or herbal supplements unless approved by investigators.
  • 13. Medications not explicitly listed as excluded will be discussed with investigator and medical monitor; inclusion decisions by clinical judgement.

Exclusion Criteria

  • Psychiatric Exclusion Criteria:
  • 1. Current major depressive disorder (MDD) within 12 months, current or past schizophrenia, psychotic disorder (unless substance-induced or medical), bipolar I/II, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, antisocial personality disorder, or judged incompatible with safe exposure to psilocybin per MINI 7.0.2 and specialist assessment.
  • 2. First-degree relative with a diagnosed psychotic disorder.
  • 3. Scores indicating clinically significant suicide risk on S-STS or psychiatric assessment; referral to medical monitor as needed.
  • 4. Attempted suicide in the 12 months preceding screening.
  • 5. Current (<1 year) alcohol or drug abuse (moderate/severe by DSM-5 via MINI 7.0.2) or unwilling/unable to abstain from alcohol 12 hours prior to dosing.
  • 6. Any reason preventing engagement in preparatory/integration sessions.
  • 7. Previous use of psychedelics within 12 months prior to screening.
  • Medical Exclusion Criteria:
  • 1. Brain metastases, glioblastoma, phaeochromocytoma, bowel obstruction/intestinal failure, active carcinoid syndrome, uncontrolled hypercalcaemia, uncontrolled diabetes mellitus/insipidus.
  • 2. Current or planned use of typical/atypical antipsychotics or MAO inhibitors (must discontinue for specified washout periods where allowed).
  • 3. Current or planned use of anticonvulsants or mood stabilizers (carbamazepine, lithium, phenytoin, valproate) unless discontinued per protocol.
  • 4. SSRI/SNRI use within last 3 months or planned initiation before Day 70.
  • 5. Any fungal allergy.
  • 6. Positive pregnancy test at screening, breastfeeding, or unwilling/unable to use effective contraception during study and for 1 month post-dose (men must agree to contraception for 90 days post-dose).
  • 7. Diagnosis of epilepsy or significant seizure risk.
  • 8. Recent (<1 year) stroke or MI, uncontrolled hypertension (>140/90) or clinically significant arrhythmia at screening unless judged related to cancer and safe for dosing.
  • 9. Clinically significant findings on exam or labs (HR <40 or >120 bpm, BP <90/60 or >140/90, ECG QTcF >450 ms males, >470 ms females); breath alcohol positive.
  • 10. Liver dysfunction ALT/AST >1.5×ULN unless due to cancer and judged safe.
  • 11. eGFR <60 mL/min unless due to cancer and judged safe.
  • 12. Any other clinically significant lab abnormality or illness posing risk for psilocybin administration.
  • 13. BMI <18 or >32 kg/m2 at screening.
  • 14. Organic brain injury or diagnosed cognitive impairment.
  • 15. Positive urine drug test for non-prescribed psychoactives at dosing; positive screen at screening referred to medical monitor.
  • 16. Participation in another investigational drug study within 3 months of enrollment.

Study Details

Locations

Unknown facility — Australia

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