CompletedPhase 1ACTRN12622000289718

A Phase I Clinical Trial of IHL-675A to Assess Safety and Pharmacokinetics in Healthy Volunteers

Sponsor

Incannex Healthcare Ltd

Enrollment

36 participants

Start Date

Aug 31, 2022

Study Type

Interventional

Conditions

Inflammation

Summary

This is a phase I clinical trial designed to assess the pharmacokinetics and safety and tolerability of IHL-675A compared to the reference listed drugs Epidiolex (CBD) and Plaquenil (HCQ). The trial will recruit at least 36 healthy subjects. Initially, 3 sentinels will be enrolled and randomised into Treatment 1, 2, and 3. Treatment 1 - Two IHL-675A softgel capsules (75mg CBD, 100 mg hydroxychloroquine sulfate per capsule, 150 mg CBD, 200 mg hydroxychloroquine sulfate total). Treatment 2: One 200mg hydroxychloroquine sulfate tablet (Plaquenil), Treatment 3: 1.5mL of 100 mg/mL (150 mg) CBD (Epidiolex) 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. The healthy subjects will be informed of the study and pre-screened. Screening will include blood and urine tests, screening for mental and cardiac health using a series of mental health questionnaires and 12-lead ECG in triplicate, respectively. Post screening, subjects will be admitted to the clinical unit, where they will undergo baseline assessments, including safety bloods and urine sampling to screen for pregnancy and drugs of abuse. On Day 1, subjects will be given a high-fat/high-calorie meal 30 minutes prior to dosing. At least 30 min before the time of dosing, the 24-hour telemetry period for cardiac monitoring will commence. Blood samples for plasma pharmacokinetic analysis, will be taken throughout the study. These samples will be assessed for the Active Pharmaceutical Ingredients as well as metabolites 7-OH-CBD and 7-COOH-CBD, and desethylhydroxychloroquine, desethylchloroquine, and bisdesethylhydroxychloroquine. Blood samples will also be taken for safety analysis. 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 any 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.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria30

Healthy volunteers will be included in the study if they satisfy all the following criteria:
Ages 18 to 65
BMI 18 to 32
QTcF <450 msec (males), <470 msec (females) at screening
No known allergic reaction to cannabis products with previous use
No known allergic reaction to sesame oil (Epidiolex is formulated in sesame oil)
Have no history of past substance abuse or current abuse of illicit drugs as defined by
a negative DOA test at screening
Physically well, in the opinion of the investigator, with no severe psychiatric, cardiac, renal, endocrine, gastrointestinal, bleeding, thyroid, cholesterol, or hypertension disorders
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.
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
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.
Not taking any vitamins, herbal remedies, or supplements within 14 days of admission
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
Agrees to eat a full fat breakfast within 30 minutes of administration of the IP
Voluntarily consent to participate in the study and complete all study required tasks, as instructed by the protocol, including the completion of questionnaires

Exclusion Criteria16

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
Family history of QT issues
History of significant psychiatric illness (defined as hospitalisation), suicidal ideation, or suicidal attempts
History of alcohol abuse or excessive alcohol intake
Positive urine drug test at screening
Positive alcohol breath test at screening
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
Any dietary requirements incompatible with study breakfast; must be able to eat high-fat, high-calorie diet
In the opinion of the investigator other serious medical conditions
Hepatic or renal impairment or disease. Defined as AST/ALT greater than 1.5 x ULN, eGFR less than 60 at screening.
Subject has a history of cardiac disease or arrythmias
History of gastrointestinal disorders which may impact absorption, distribution, metabolism and/or excretion of the IP (such as cholecystitis, cholecystectomy, Gilbert’s syndrome)
Inability to adhere to medication restrictions during the study period
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.
Inability to adhere to the protocol
Any other reason in the opinion of the investigator

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Interventions

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 vol

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.