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Trial registered on ANZCTR


Registration number
ACTRN12622000289718
Ethics application status
Approved
Date submitted
15/09/2021
Date registered
15/02/2022
Date last updated
30/06/2023
Date data sharing statement initially provided
15/02/2022
Date results provided
30/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I Clinical Trial of IHL-675A to Assess Safety and Pharmacokinetics in Healthy Volunteers
Scientific title
A Phase I Clinical Trial of IHL-675A to Assess Safety and Pharmacokinetics in Healthy Volunteers
Secondary ID [1] 305308 0
IHL675APh1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammation 323624 0
Condition category
Condition code
Inflammatory and Immune System 321159 321159 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This phase I clinical trial is designed to assess the pharmacokinetics and safety and tolerability of IHL-675A compared to the reference listed drugs Epidiolex (CBD) and Plaquenil (HCQ).
Healthy volunteers will be enrolled and randomised to receive 1 of 3 treatments;
• Treatment 1: Two IHL-675A softgel capsules (75mg CBD, 100 mg hydroxychloroquine sulfate per capsule, 150 mg CBD, 200 mg hydroxychloroquine sulfate total). Treatment 1-two softgel caps- will be administered orally, with a glass of water.
• Treatment 2: One 200mg hydroxychloroquine sulfate tablet (Plaquenil). Treatment 2- one Plaquenil tablet will be administered orally, with a glass of water.
• Treatment 3: 1.5mL of 100 mg/mL (150 mg) CBD (Epidiolex) Treatment 3 - 1.5ml of Epidiolex (liquid) will be administered orally, via an oral syringe.
Initially, 3 sentinels will be enrolled and randomised into Treatment 1, 2, and 3. The sentinels will be dosed at least 24 hours prior to the remainder of the subjects. If there are serious adverse events associated with the dose the trial will be paused and the risk of further subjects receiving IHL-675A will be assessed.
Each Treatment group will enrol at least 12 subjects each, for a total of at least 36 subjects. Subjects will be randomised into the treatment groups.

Screening procedures, which include mental health questionnaires, ECG and safety bloods will determine eligibility.
After the screening period (maximum 28 days), subjects will be admitted to the clinical unit, undergo baseline assessments, including safety bloods and urine sampling to screen for pregnancy and drugs of abuse. On Day 1 (the day of dosing), subjects will be given a high-fat/high-calorie meal 30 minutes prior to dosing. This high fat meal consists of 2 fried eggs, bacon, 2 slices of white toast with butter, hash brown potatoes and a glass of full cream milk. (Note the high fat meal is based on the FDA Guidance for Industry Food-Effect Bioavailability and Fed Bioequivalence Studies of (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories)). The meal must be consumed within 30 minutes. At least 30 minutes before the time of dosing, the 24-hour telemetry period for cardiac monitoring will commence. Blood samples for pharmacokinetic analysis, including one pre-dose sample, will be taken throughout the study period. These samples will be assessed for the Acitve Pharmaceutical Ingredients (APIs) as well as metabolites 7-OH-CBD and 7-COOH-CBD, and desethylhydroxychloroquine, desethylchloroquine, and bisdesethylhydroxychloroquine. Blood samples will also be taken from screening to Day 7 for safety analysis and will include the following analytes: blood cell count, Follicle Stimulating Hormone (FSH), electrolytes, urea, and liver enzymes.
Subjects are discharged from the clinical unit on Day 2, at least 24 hours post dose, and will return to the clinical unit for outpatient visits on Days 3, 7, 14, 21, and 28 for blood sampling and/or to assess existing or new Adverse Events and concomitant medications.
Subjects who have completed Cohort 1 and who continue to meet study entry criteria may be permitted to screen for participation in Cohort 3.
Intervention code [1] 321727 0
Treatment: Drugs
Comparator / control treatment
Two comparator drugs will be used in this trial: Epidiolex (CBD) and Plaquenil (HCQ)
Subjects allocated to Cohort 1-Epidiolex (reference listed drug for cannabidiol) will receive one dose of 100mg/ml Epidiolex (CBD-oil ). While subjects in Cohort 2- Plaquenil (reference listed drug for hydroxychloroquine sulfate) will receive 200mg HCQ, in tablet form.
Control group
Active

Outcomes
Primary outcome [1] 328971 0
To Assess the plasma pharmacokinetics of the active pharmaceutical ingredients HCQ as well as its major metabolites, desethylhydroxychloroquine, desethylchloroquine, and bisdesethylhydroxychloroquine in cohort 2 and 3.
Timepoint [1] 328971 0
The timepoints for all plasma pharmacokinetic samples taken for analysis in cohort 2 and 3 for HCQ and its metabolites are at pre-dose administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24hr, Day 3, 7, 14, 21 and 28. The parameters for testing are Cmax (Maximum observed drug concentration), Tmax (Time of the maximum drug concentration), AUC0-last (Area under the drug concentration-time curve, from time zero to time of the last measurable concentration), AUC0-inf (Area under the drug concentration-time curve from time zero to infinity), AUC0-12h (Area under the drug concentration-time curve from time zero to 12 hours), AUC0-24h (Area under the drug concentration-time curve from time zero to 24 hours), .t1/2 (Terminal elimination half-life), kel (Terminal elimination rate constant), CL/F (Apparent total body clearance) and .
Vz/F (Apparent volume of distribution).
Primary outcome [2] 329256 0
To Assess the plasma pharmacokinetics of IHL-675A for subjects in cohort 3, compared to the reference listed drugs Plaquenil (Hydroxychloroquine sulfate), and Epidiolex (Cannabidiol) taken by subjects in cohorts 1 and 2.
Timepoint [2] 329256 0
The timepoints for all plasma pharmacokinetic samples taken for analysis are at pre-dose administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24hr, Day 3, 7, 14, 21 and 28. The parameters for testing are Cmax (Maximum observed drug concentration), Tmax (Time of the maximum drug concentration), AUC0-last (Area under the drug concentration-time curve, from time zero to time of the last measurable concentration), AUC0-inf (Area under the drug concentration-time curve from time zero to infinity), AUC0-12h (Area under the drug concentration-time curve from time zero to 12 hours), AUC0-24h (Area under the drug concentration-time curve from time zero to 24 hours), .t1/2 (Terminal elimination half-life), kel (Terminal elimination rate constant), CL/F (Apparent total body clearance) and .
Vz/F (Apparent volume of distribution).
Primary outcome [3] 328970 0
To Assess the plasma pharmacokinetics of the active pharmaceutical ingredients CBD as well as its major metabolites, 7-OH-CBD, and 7-COOH-CBD in cohort 1 and 3.
Timepoint [3] 328970 0
The timepoints for all plasma pharmacokinetic samples taken for analysis in cohort 1 and 3 for CBD and its metabolites are at pre-dose administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24hr, Day 3, Day 7, 14, 21 and 28. The parameters for testing are Cmax (Maximum observed drug concentration), Tmax (Time of the maximum drug concentration), AUC0-last (Area under the drug concentration-time curve, from time zero to time of the last measurable concentration), AUC0-inf (Area under the drug concentration-time curve from time zero to infinity), AUC0-12h (Area under the drug concentration-time curve from time zero to 12 hours), AUC0-24h (Area under the drug concentration-time curve from time zero to 24 hours), .t1/2 (Terminal elimination half-life), kel (Terminal elimination rate constant), CL/F (Apparent total body clearance) and .
Vz/F (Apparent volume of distribution).
Secondary outcome [1] 401001 0
To Assess the safety and tolerability of IHL-675A
Timepoint [1] 401001 0
Safety and tolerability to be assessed by blood tests, assessing haematology, serum chemistry, liver function, urinalysis at screening (Day -28 to Day -3), on admission at Visit Day-1, then on Dosing Day,(Day 1) at 3 hours post dose and Dosing Day 24 hours post dose, and post discharge at follow up visit Day 7.
Secondary outcome [2] 401002 0
To monitor any changes to cardiac parameters, such as resting heart rate, sinus rhythm, Ventricular events, Supraventricular events, Arrythmia and ST Level
Timepoint [2] 401002 0
Cardiac monitoring using 12 lead ECGs, done in triplicate, at Screening, Day-1 (Admission), pre-dose (Day 1 at -1 hour) then at 3hours, 24hours, 48 hours and at Day 7 post dose to monitor any possible impact of the investigational product(s) on QT interval.
Secondary outcome [3] 401003 0
To monitor any possible effect of the investigational product(s) on cardiac rhythm, respiratory rate and arterial oxygen saturation
Timepoint [3] 401003 0
Cardiac monitoring using telemetry, continuously beginning from Day 1-30 minutes pre-dose and continuously through from dosing to post dose Day 2 to observe any possible effect of the investigational product(s) on cardiac rhythm, respiratory rate and arterial oxygen saturation

Eligibility
Key inclusion criteria
Healthy volunteers will be included in the study if they satisfy all the following criteria:

1. Ages 18 to 65

2. BMI 18 to 32

3. QTcF <450 msec (males), <470 msec (females) at screening

4. No known allergic reaction to cannabis products with previous use

5. No known allergic reaction to sesame oil (Epidiolex is formulated in sesame oil)

6. Have no history of past substance abuse or current abuse of illicit drugs as defined by
a negative DOA test at screening

7. Physically well, in the opinion of the investigator, with no severe psychiatric, cardiac, renal, endocrine, gastrointestinal, bleeding, thyroid, cholesterol, or hypertension disorders

8. If male, agree to be sexually abstinent or agree to use two approved methods of contraception when engaging in sexual activity from 14 days prior to Visit Day 1 through to the end of the study. Subjects must agree to continue to use two approved methods of contraception including the use of a condom for 90 days following the administration of the study drug, and not donate sperm during this same period of time. In the event that the sexual partner is surgically sterile, contraception is not necessary.
a. Approved methods of contraception;
i. Inter-uterine device (IUD) in place for at least 3 months prior to Visit Day 1 through 30 days following the final dosing of the study drug
ii. Barrier method (condom or diaphragm) for at least 14 days prior to Visit Day 1 through to 90 days following the last administration of the study drug.
iii. Stable hormonal contraceptive for at least 3 months prior to Visit Day 1 and barrier method (condom or diaphragm) for at least 14 days prior to Visit Day 1 through to 90 days following the last administration of the study drug.
iv. Surgical sterilization (vasectomy) at least 6 months prior to Visit Day 1.

9. Females of non-childbearing potential who have established serum FSH levels >40mlU/ml (determined during screening) are either postmenopausal or have undergone one of the following sterilization procedures at least 6 months prior to Visit Day 1;
a. Bilateral tubal ligation
b. Hysterectomy
c. Hysterectomy with unilateral or bilateral oophorectomy
d. Bilateral oophorectomy

10. Females of childbearing potential that are not currently pregnant, lactating, or planning to be pregnant and agree to be sexually abstinent or agree to use two approved methods of contraception when engaging in sexual activity from 14 days prior to Visit Day 1 through to the end of the study. Subjects must agree to continue to use two approved methods of contraception for 30 days following the administration of the study drug. In the event that the sexual partner is surgically sterile, contraception is not necessary.
a. Approved methods of contraception to use in conjunction with a condom;
i. Inter-uterine device (IUD) in place for at least 3 months prior to Day 1 through 30 days following the final dosing of the study drug
ii. Barrier method (condom or diaphragm) for at least 14 days prior to Day 1 through to 30 days following the last administration of the study drug.
iii. Stable hormonal contraceptive for at least 3 months prior to Visit Day 1 and barrier method (condom or diaphragm) for at least 14 days prior to Visit Day 1 through to 30 days following the last administration of the study drug.
iv. Surgical sterilization (vasectomy) at least 6 months prior to Visit Day 1.

11. Not taking any vitamins, herbal remedies, or supplements within 14 days of admission

12. Able to avoid strenuous exercise from 72 hours prior to admission through to the end of the confinement period (Visit Day 2), and 72 hours prior to Visit Day 7 until the Day 7 outpatient visit is complete

13. Agrees to eat a full fat breakfast within 30 minutes of administration of the IP

14. Voluntarily consent to participate in the study and complete all study required tasks, as instructed by the protocol, including the completion of questionnaires
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy volunteers will be excluded from the study if there is evidence of any of the following at screening, or prior to dosing at the timepoints in the Schedule of Events
1. Family history of QT issues

2. History of significant psychiatric illness (defined as hospitalisation), suicidal ideation, or suicidal attempts

3. History of alcohol abuse or excessive alcohol intake

4. Positive urine drug test at screening

5. Positive alcohol breath test at screening

6. GAD-7 score of 15 or greater, MDI score 31 or greater OR 3 core symptoms and 5 accompanying symptoms, C-SSRS score of 4 or greater, OR reported suicidal behaviour within the past 3 months

7. Any dietary requirements incompatible with study breakfast; must be able to eat high-fat, high-calorie diet

8. In the opinion of the investigator other serious medical conditions

9. Hepatic or renal impairment or disease. Defined as AST/ALT greater than 1.5 x ULN, eGFR less than 60 at screening.

10. Subject has a history of cardiac disease or arrythmias

11. History of gastrointestinal disorders which may impact absorption, distribution, metabolism and/or excretion of the IP (such as cholecystitis, cholecystectomy, Gilbert’s syndrome)

12. Inability to adhere to medication restrictions during the study period

13. Participation in another clinical trial of an investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to study drug administration.

14. Inability to adhere to the protocol

15. Any other reason in the opinion of the investigator

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Cohort 1 will be filled and completed prior to cohort 2 commencing. Similarly, cohort 3 will commence post completion of cohort 2.
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
A total of at least 36 healthy volunteers will be enrolled in a total of 3 cohorts. Each cohort will enrol 12 subjects. Each participant will be enrolled into one of these cohorts.
The sample size was selected as 12 is the minimum sample size recommended for bioequivalence studies in the FDA guidance on Statistical Approaches to Establishing Bioequivalence .

In general, data will be summarized using descriptive statistics (number of non-missing observations, mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data. Where appropriate, missing values will be marked and explained in individual data tables. Baseline will be defined as the last available, valid, non-missing assessment prior to dosing.
Only data from protocol scheduled visits/time points will be included in the summary tables. Data from unscheduled visits/time points will not be included in the summary tables but will be included in the figures and listings.
Demographic and other baseline data will be presented with summary statistics.
Results for the cardiac monitor telemetry will be analysed by the investigator and/or delegated research staff, qualified to review and comment on the data generated.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2022
Actual
31/08/2022
Date of last participant enrolment
Anticipated
31/10/2022
Actual
28/09/2022
Date of last data collection
Anticipated
4/11/2022
Actual
26/10/2022
Sample size
Target
36
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 20526 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 35306 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 309675 0
Commercial sector/Industry
Name [1] 309675 0
Incannex Healthcare Ltd
Country [1] 309675 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Incannex Healthcare Ltd
Address
105 / 8 Century Circuit,
Norwest, 2153
New South Wales
Australia
Country
Australia
Secondary sponsor category [1] 310712 0
None
Name [1] 310712 0
Address [1] 310712 0
Country [1] 310712 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309443 0
Bellberry Limited
Ethics committee address [1] 309443 0
Ethics committee country [1] 309443 0
Australia
Date submitted for ethics approval [1] 309443 0
15/09/2021
Approval date [1] 309443 0
20/07/2022
Ethics approval number [1] 309443 0

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

Contacts
Principal investigator
Name 114178 0
Dr Jonathan Newchurch
Address 114178 0
CMAX Clinical Research
Level 5, 18a North Terrace
Adelaide 5000
South Australia
Country 114178 0
Australia
Phone 114178 0
+61 423 223 756
Fax 114178 0
+61 8 7088 7999
Email 114178 0
cmax@cmax.com.au
Contact person for public queries
Name 114179 0
Jonathan Newchurch
Address 114179 0
CMAX Clinical Research
Level 5, 18a North Terrace
Adelaide 5000
South Australia
Country 114179 0
Australia
Phone 114179 0
+61 8 7088 7900
Fax 114179 0
+61 8 7088 7999
Email 114179 0
cmax@cmax.com.au
Contact person for scientific queries
Name 114180 0
Jonathan Newchurch
Address 114180 0
CMAX Clinical Research
Level 5, 18a North Terrace
Adelaide 5000
South Australia
Country 114180 0
Australia
Phone 114180 0
+61 8 70887900
Fax 114180 0
+61 8 7088 7999
Email 114180 0
cmax@cmax.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will be commercially sensitive


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.