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

Exclusion Criteria77

• Current major depressive disorder (MDD) (or within 12 months of Screening),
• current or past diagnosis of schizophrenia, psychotic disorder, unless this was
• substance-induced or resulting from a medical condition (e.g. lupus or malaria etc.),
• bipolar disorder I and II, delusional disorder, paranoid personality disorder,
• schizoaffective disorder, borderline personality disorder, anti-social personality
• disorder or judged to be incompatible with establishment of rapport or safe exposure
• to psilocybin, as assessed through medical history and the Mini Neuropsychiatric
• Inventory (MINI 7.0.2) by any specialist psychiatrist or registered medical
• professional under the authorized delegation of a specialist psychiatrist.
• First-degree relative with a diagnosed psychotic disorder.
• Scores from the screening psychiatrist (or registered medical professional under
• the authorized delegation of a specialist psychiatrist) and baseline (S-STS) indicate
• that the participant is of clinically significantrisk ofsuicide. A decision will be formed
• based on S-STS scores and used in combination with other clinically significant data
• at screening. Sites should refer to the medical monitor if required.
• Has attempted suicide in the 12 months preceding the screening visit.
• Current (< 1 year) alcohol or drug abuse asidentified as moderate or severe during screening in accordance with Diagnostic and Statistical Manual of Mental Disorders
• (DSM-5) criteria, using the MINI 7.0.2, not able or willing to abstain from alcohol
• consumption in the period 12 hours prior to the dosing session.
• Any other reason that might prevent a participant from engaging in therapeutic
• preparation and integration sessions.
• Previous use of psychedelics within 12 months preceding screening.
• Diagnosed with brain metastases, glioblastoma, phaeochromocytoma, bowel
• obstruction or intestinal failure, active carcinoid syndrome, uncontrolled
• hypercalcaemia, or uncontrolled diabetes mellitus or insipidus.
• Currently taking or planning to take any of the following: any typical or atypical
• antipsychotic and monoamine-oxidase inhibitors. Participants with prior use of these
• medications must be willing to discontinue their use for at least 2 weeks prior to the
• baseline visit and to Day 28.
• Currently taking or planning to take any anticonvulsant or mood stabilizer,
• including carbamazepine, lithium, phenytoin, and valproate. Participants with prior
• use of these medications must be willing to discontinue their use for at least 1 week
• prior to the baseline visit and to Day 28.
• Participants who have taken selective serotonin reuptake inhibitor/serotoninnorepinephrine reuptake inhibitor (selective and norepinephrine reuptake inhibitor
• [SNRI] and selective serotonin reuptake inhibitor [SSRI]) within the last 3 months
• and/or who are planning to initiate them before Day 70 of their study participation.
• Any form of fungal allergy.
• Positive pregnancy test at screening, women who are breastfeeding or of
• childbearing potential who are unwilling or unable to use an effective form of
• contraception (or abstinence) for the study period and for 1 month post PEX010 dose
• will be excluded. Women will be required to conduct a serum pregnancy test at the
• in-person screening visit and urine test prior to dosing session. Male participants who
• do not agree to use contraception for the study period and for 90 days post PEX010
• dose to mitigate the risk of pregnancy will also be excluded. Note: Refer to Section
• 3.2.1 for further details about contraception.
• A diagnosis of epilepsy or at significant risk of seizures based on medical history.
• Cardiovascular conditions including stroke and/or myocardial infarction (less than
• one year before providing informed consent), uncontrolled hypertension (blood
• pressure > 140/90 mmHg) or clinically significant arrhythmia at screening. Results
• are exempt if they are a direct result of the participant’s cancer diagnosis and do not
• present a risk to administration of psilocybin, following discretion of the investigator.
• Anyone who, at screening, has clinically significant findings on physical
• examination, including resting vital signs (heart rate below 40 or above 120 bpm,
• blood pressure below 90/60 or above 140/90), ECG (QTcF > 450 msec for males
• and >470 for females), and positive alcohol breath test. Note: Testing for any outof-range values may be repeated at the discretion of the Investigator.
• Liver dysfunction at screening as defined by ALT/AST >1.5 times the upper limit of
• normal or upper reference range. Results are exempt if they are a direct result of the
• participant’s cancer diagnosis and do not present a risk to the administration of
• psilocybin, following discretion of the investigator.
• Renal Function: estimated glomerular filtration rate <60 mL/min (calculated
• using Chronic Kidney Disease Epidemiology Collaboration) unless this is a direct
• result of the cancer diagnosis and does not present a risk to the administration of
• psilocybin, following the discretion of the investigator.
• Any clinically significant laboratory abnormality(s) that in the opinion of the
• investigator would present a risk to the administration of psilocybin.
• Any clinically significant renal, pulmonary, gastrointestinal, hepatic, or other
• illness that could affect the interpretation of results or be a potential health risk for
• the person if they were to be included in the study. Results are exempt if they are a direct result of the participant’s cancer diagnosis and do not present a risk to
• administration of psilocybin, following discretion of the investigator.
• Below 18 or above 32 kg/m2 Body Mass Index (BMI) score at Screening.
• Anyone with organic brain injury or diagnosed with any cognitive impairment.
• Positive urine drug test for non-prescribed psychoactive substances at the Dosing
• sessionvisit. Positive urine drug test for psychoactive substances at the in-person
• screening should be referred to the medical monitor. Note: Testing may be repeated
• once at the discretion of the Investigator.
• Anyone on a research study of an investigational drug or who has been on a
• clinical trial within 3 months of enrollment.