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Trial registered on ANZCTR


Registration number
ACTRN12623000423617
Ethics application status
Approved
Date submitted
3/04/2023
Date registered
28/04/2023
Date last updated
29/05/2024
Date data sharing statement initially provided
28/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
LUCID-201-001: A Double-Blind, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Lucid-201 in Healthy Male and Female Volunteers and Patients with Depressive Symptoms on a selective-serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI)
Scientific title
A Double-Blind, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Lucid-201 in Healthy Male and Female Volunteers and Patients with Depressive Symptoms on a selective-serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI)
Secondary ID [1] 309279 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mental Health 329437 0
Condition category
Condition code
Mental Health 326380 326380 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Double-blind, single ascending dose (SAD) study in healthy male and female volunteers and patients with symptoms of depression on stable doses on SSRI or SNRI medications. Doses will be administered under fasting conditions (no food or drink for 8 hours prior to dosing and 5 hours post dose). Dosing will be verified via mouth checks to confirm all tablets are swallowed.
Four cohorts consisting of healthy volunteers and two cohorts consisting of patients with mild-to-moderate symptoms of depression on SSRI or SNRI medications receiving either single ascending doses of Lucid-201 or 100 mg niacin (n = 8 per cohort, randomized as six Lucid-201, two niacin), as follows:
• Cohort 1 (healthy volunteers): One Lucid-201 tablet or 100 mg niacin
• Cohort 2 (healthy volunteers): Two Lucid-201 tablets or 100 mg niacin
• Cohort 3 (healthy volunteers): Four Lucid-201 tablets or 100 mg niacin
• Cohort 4 (healthy volunteers): Six Lucid-201 tablets or 100 mg niacin
• Cohort 5 (patients with depressive symptoms): Two Lucid-201 tablets or 100 mg niacin
• Cohort 6 (patients with depressive symptoms): Six Lucid-201 tablets or 100 mg niacin

The intervention for all participants will be completed on site over a 3 day, 2 night period to allow for all assessments to be completed pre and post dose.
Intervention code [1] 325715 0
Treatment: Drugs
Comparator / control treatment
Oral tablet administration of active placebo (100mg niacin) with mouth checks to confirm compliance
Control group
Active

Outcomes
Primary outcome [1] 334234 0
• To assess the safety and tolerability of single ascending doses of orally administered Lucid-201 in healthy participants and patients with symptoms of depression on stable doses of SSRI or SNRI.

Common physical side effects (light headedness, mild headaches, mild nausea, sore muscles, elevated blood pressure, elevated heart rate and hormone levels) will all be monitored and assessed post dose for up to 24 hours by medical staff. Psychological assessments will also be completed during the post dose period.

Safety and tolerability will be assessed via collection of AEs, vital signs; including heart rate, blood pressure (with sphygmomanometer), respiratory rate and temperature (with thermometer), ECG, clinical laboratory tests, physical examination, concomitant medications, Columbia- Suicide Severity Rating Scale (C-SSRS), and HAM-D (for cohorts 5 and 6). Self reported and investigator assessed questionnaires will also be used.
Timepoint [1] 334234 0
Baseline and throughout the dosing period. A follow-up assessment will also take place at the two-week timepoint.
Primary outcome [2] 334235 0
• To assess the pharmacokinetics of single ascending doses of orally administered Lucid-201 in healthy participants and patients with symptoms of depression on stable doses of SSRI or SNRI.

PK assessments will be based on blood samples taken at specified pre-dose and post-dose time points throughout the trial
Timepoint [2] 334235 0
Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 18, and 24 hr post-dose.
Secondary outcome [1] 419927 0
Visual Analogue Scale (VAS)
a. Any Effects VAS: rate the subjective intensity of the effects from the administered drug
Timepoint [1] 419927 0
Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hr post-dose.
Secondary outcome [2] 420725 0
Mystical Experience Questionnaire to self report what degree they experienced
phenomenon consistent with mystical, psychedelic experiences.
Timepoint [2] 420725 0
At 8 hr post-dose.
Secondary outcome [3] 420726 0
5-Dimensional Altered States of Consciousness is a self report scale for alterations from normal waking consciousness
Timepoint [3] 420726 0
At 8 hr post-dose.
Secondary outcome [4] 420727 0
Challenging Experiences Questionnaire is a self report to reflect on a psychedelic experience.
Timepoint [4] 420727 0
At 8 hr post-dose.
Secondary outcome [5] 420728 0
Persisting Effects Questionnaire self report to assess possible change in attitudes, mood, behaviors, and spiritual experiences
Timepoint [5] 420728 0
2 weeks post dose
Secondary outcome [6] 420729 0
State Trait Anxiety Inventory self report to assess for trait anxiety and state anxiety.
Timepoint [6] 420729 0
Pre-dose and at 8 and 24 hr post-dose as well as 2 weeks post dose
Secondary outcome [7] 421350 0
Visual Analogue Scales (VAS)
b. Good Drug Effects VAS: rate the extent to which they are experiencing positive effects
Timepoint [7] 421350 0
Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hr post-dose.
Secondary outcome [8] 421351 0
Visual Analogue Scales (VAS)
c. Bad Drug Effects VAS: rate the extent to which they are experiencing negative effects
Timepoint [8] 421351 0
Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hr post-dose.
Secondary outcome [9] 421352 0
Visual Analogue Scales (VAS)
d. Hallucinations VAS: rate the intensity of hallucinations
Timepoint [9] 421352 0
Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hr post-dose.
Secondary outcome [10] 421353 0
Visual Analogue Scales (VAS)
e. Drug Intensity VAS: rate the subjective intensity of the administered drug
Timepoint [10] 421353 0
Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hr post-dose.

Eligibility
Key inclusion criteria
Inclusion Criteria (cohorts 1 – 4):

1. Healthy male and female volunteers, 18 – 60 years of age, inclusive at the time of informed consent.
2. Body mass index (BMI) that is within 18.0 – 32.0 kg/m2, inclusive, and minimum weight of 50 kg.
3. Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
4. QTcF interval less than or equal to 450 msec for males and less than or equal to 470 msec for females, unless deemed otherwise by the PI/Sub-Investigator.
5. Systolic blood pressure between 90 – 140 mmHg, inclusive, and diastolic blood pressure between 40 – 90 mmHg, inclusive, and heart rate between 40 – 100 bpm, inclusive, unless deemed otherwise by the PI/Sub-Investigator.
6. Clinical laboratory values within the most recent acceptable laboratory test ranges and/or values are deemed by the PI/Sub-Investigator as “Not Clinically Significant.”
7. Non-smoker, for at least 30 days prior to trial drug administration.
8. Ability to comprehend and be informed of the nature of the trial, as assessed by PI. Capable of giving written informed consent prior to any trial related procedure. Must be able to communicate effectively with clinic staff.
9. Ability to speak, read, and understand English sufficiently to allow completion of all trial assessments.
10. Ability to fast for at least 13 hours and the ability to consume standard meals.
11. Availability to volunteer for the entire trial duration and willing to adhere to all protocol requirements.
12. Agree not to have a tattoo or body piercing until the end of the trial.
13. Agree not to receive the COVID-19 vaccination or any other vaccination from seven days prior to the trial drug dose until after the follow-up visit.
14. Agree not to drive or operate heavy machinery if feeling dizzy, drowsy, or otherwise mentally impaired following trial drug administration until full mental alertness is regained.
15. Female participants must be non-pregnant and non-lactating and fulfill at least one of the following:
a. Be surgically sterile for a minimum of six months (achieved through hysterectomy, oophorectomy, or bilateral salpingectomy; note that tubal ligation is not considered a method of permanent sterilization).
b. Post-menopausal for a minimum of one year (postmenopausal is defined as twelve consecutive months with no menses without an alternative medical cause). An FSH test will be performed to confirm post-menopausal status.
c. Agree to avoid pregnancy and use an acceptable effective method of contraception with male sexual partners from at least 30 days prior to the trial until at least 30 days after the follow-up visit.
d. Acceptable effective methods of contraception include using a male condom in combination with oral contraceptives, hormonal patch, implant or injection, hormonal or /non-hormonal intrauterine device; or a double-barrier method (e.g., male condom in addition to pill, implant, or IUD). Abstinence as a method of contraception is acceptable if it is in line with the preferred and usual lifestyle of the trial participant. Female participants with a vasectomised male partner are required to adhere to the acceptable contraception methods.
16. Males who are able to father children must agree to use an acceptable effective method of contraception with female sexual partners of child-bearing potential and not donate sperm during the trial and for at least 30 days after the last dose of the trial drug (Lucid-201 or placebo).
a. Acceptable effective methods of contraception include using a male condom with a female sexual partner of child-bearing potential who is using oral contraceptives, hormonal patch, implant or injection, intrauterine device or system; or a double-barrier method (e.g., male condom in addition to pill, implant, or IUD). Abstinence as a method of contraception is acceptable if it is in line with the preferred and usual lifestyle of the trial participant.
b. Vasectomised male participants are required to use a condom as the acceptable contraception method if they are sexually active with a female partner.
c. Male participants who have a female sexual partner who is surgically sterile or post-menopausal are required to use a condom as the acceptable contraception method.
d. Male participants who have a male sexual partner are required to use a condom as the acceptable contraception method
17. If a participant’s partner becomes pregnant during his participation in the trial and for 30 days after he has completed his last trial drug administration, he must inform site staff immediately.Deemed suitable for dosing with a psychedelic by the PI/Sub-Investigator and/or clinical staff.

Inclusion Criteria (Cohorts 5 and 6)
Criterion 1 has been changed to the following:
• Male and female volunteers, 18 – 60 years of age, inclusive at the time of informed consent.
Criterion 2 has been changed to the following:
• Body mass index (BMI) that is within 18.0 – 35.0 kg/m2, inclusive, and minimum weight of 50 kg.
Two additional criteria have been added:
• Presence of current depressive symptoms with mild-to-moderate severity (as measured by the Hamilton-Depression Rating Scale (HAM-D), scores greater than or equal to 8 but <24).
• Current treatment using a single selective-serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) with a stable dose for two months.

All other inclusion criteria from Cohorts 1 – 4 apply.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria (cohorts 1 – 4):
1. Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
2. Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within seven days prior to first trial drug administration, as determined by the PI/Sub-Investigator.
3. History of seizures, including once off for both the participant and their first-degree relatives with history of seizures, history of head trauma with the exception of fully resolved minor concussions (no hospitalization or loss of consciousness), history of neurosurgery, or first-degree relatives with idiopathic generalized epilepsy or other congenital epilepsies.
4. Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
5. Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
6. A positive test result for human immunodeficiency virus (HIV), chronic Hepatitis B surface antigen, or Hepatitis C.
7. A positive test result for drugs with abuse potential (amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinol), alcohol (via breathalyzer test), and/or cotinine.
8. Positive pregnancy test for female participants.
9. Known history or presence of:
a. Hypersensitivity or idiosyncratic reaction to psilocybin, psilocin and/or related substances and/or excipients;
b. Clinically significant food allergies;
c. Presence of any dietary restrictions unless deemed by the PI/Sub-I as “Not Clinically Significant;”
d. Severe allergic reactions (e.g., anaphylactic reactions, angioedema).
10. Psychiatric exclusion criteria:
a. Current or past history of schizophrenia spectrum, psychotic disorder (unless due to a medical condition), or bipolar I or II disorder.
b. Current or past history within the last two years of alcohol or drug dependence (excluding caffeine and nicotine).
c. Current or past history within the last five years of major depressive disorder, obsessive-compulsive disorder, panic disorder, anorexia nervosa, or bulimia nervosa.
d. Have a first-degree relative with schizophrenia spectrum, psychotic disorder (unless substance-induced or due to a medical condition), or bipolar I or II disorder.
e. Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocin.
f. Suicidal ideation or active suicidality, based on C-SSRS results.
11. Intolerance to and/or difficulty with blood sampling through venipuncture.
12. Use of psychedelics (e.g., psilocybin or ‘magic mushrooms,’ LSD, mescaline, DMT, ayahuasca) in the past two years or more than five times in lifetime.
13. Individuals who have donated, in the days prior to first trial drug administration:
a. >400 mL of blood in the previous 30 days;
b. 500 mL or more in the previous 56 days.
14. Donation of plasma by plasmapheresis within 7 days prior to trial drug administration.
15. Individuals who have participated in another clinical trial or who received an investigational drug within 30 days prior to trial drug administration.
16. Use of any enzyme-modifying drugs and/or other products, including strong inhibitors of cytochrome P450 (CYP) enzymes (e.g., cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (e.g., barbiturates, carbamazepine, glucocorticoids, phenytoin, St. John´s Wort, and rifampicin) in the previous 30 days before trial drug administration.
17. Use of any prescription medication within 14 days prior to trial drug administration (except for accepted methods of contraception). The use of topical drugs (without significant systemic absorption) may be deemed acceptable by the PI/Sub-Investigator.
18. Use of over-the-counter medications (including oral multivitamins, herbal and/or dietary supplements) within seven days prior to trial drug administration (except for accepted methods of contraception). The use of topical drugs (without significant systemic absorption) may be deemed acceptable by the PI/Sub-Investigator.
19. Consumption of food or beverages containing grapefruit and/or pomelo within 10 days prior to trial drug administration.
20. Consumption of food or beverages containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hr before dosing (includes coffee and tea).
21. Individuals having undergone any major surgery within three months prior to the start of the trial, unless deemed not clinically significant by PI/Sub-Investigator.
22. Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the trial.
23. Difficulty with swallowing tablets or capsules.
24. Have had a new tattoo or body piercing within 30 days prior to trial drug administration.
25. In the opinion of the Investigator, the participant is not suitable for the trial.

Exclusion Criteria (cohorts 5 and 6):
Criterion 4 has been changed to the following:
• Presence of any clinically significant illness – except for depressive disorders – within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
Criterion 10 has been changed to the following:
• The Psychiatric exclusion criteria: “Current or past history within the last five years of major depressive disorder” has been removed.
One additional criterion has been added:
• Presence of severe depressive symptoms (as measured by the Hamilton-Depression Rating Scale (HAM-D), scores greater than or equal to 24).


All other exclusion criteria from Cohorts 1 – 4 apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
30/11/2024
Actual
Date of last data collection
Anticipated
3/02/2025
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24326 0
Nucleus Network - Melbourne
Recruitment hospital [2] 24327 0
Nucleus Network - Geelong

Funding & Sponsors
Funding source category [1] 313212 0
Commercial sector/Industry
Name [1] 313212 0
FSD Pharma Australia Pty Ltd
Country [1] 313212 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
FSD Pharma Australia Pty Ltd
Address
Level 7 330 Collins Street, Melbourne, 3000
Country
Australia
Secondary sponsor category [1] 315265 0
None
Name [1] 315265 0
Address [1] 315265 0
Country [1] 315265 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312443 0
Alfred Health Ethics Committee
Ethics committee address [1] 312443 0
Ethics committee country [1] 312443 0
Australia
Date submitted for ethics approval [1] 312443 0
Approval date [1] 312443 0
15/03/2023
Ethics approval number [1] 312443 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124686 0
Dr Philip Ryan
Address 124686 0
Nucleus Network Pty Ltd
Level 5, 89 Commercial Road
Melbourne VIC 3004
Country 124686 0
Australia
Phone 124686 0
+61 438 009 787
Fax 124686 0
Email 124686 0
[email protected]
Contact person for public queries
Name 124687 0
Philip Ryan
Address 124687 0
Nucleus Network Pty Ltd
Level 5, 89 Commercial Road
Melbourne VIC 3004
Country 124687 0
Australia
Phone 124687 0
+61 438 009 787
Fax 124687 0
Email 124687 0
[email protected]
Contact person for scientific queries
Name 124688 0
Andrzej Chruscinski
Address 124688 0
FSD Pharma Australia
Level 7, 330 Collins Street, Melbourne, 3000, Australia
Country 124688 0
Australia
Phone 124688 0
+1 4168146057
Fax 124688 0
Email 124688 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be available


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.