Bioavailability, Bioequivalence and Tolerability of IHL-42X Compared to the Reference Drugs

NCT05857384 | Completed Phase 1 FDA Drug

• 1 other identifier: IHL42XBABE
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this randomised four-period cross-over Phase I study is to assess bioavailability, bioequivalence and tolerability of IHL-42X compared to the reference drugs in healthy volunteers. Volunteers will be enrolled and randomised to one of four treatment groups. Each group is to receive all four treatments in a twenty eight day cross-over study, with each treatment period running for seven days. The four treatment groups are described below; A = dronabinol 5 mg, fasted; B = acetazolamide 250 mg, fasted; C = IHL-42X (5 mg dronabinol, 250 mg acetazolamide), fasted; D = IHL-42X (5 mg dronabinol, 250 mg acetazolamide), fed. Each treatment group will enrol at least 29 participants each, for a total of at least 116 participants. Bioavailability and bioequivalence will assess and compare all four of the seven day treatments.

Conditions

Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (12)

• Bioavailability of IHL-42X

  Assess the proportion of IHL-42X that is taken up and enters the circulation post dose.

  28 days

• Bioequivalence of IHL-42X

  Compare the proportion of IHL-42X taken up and enters the circulation to the reference listed drugs for dronabinol and acetazolamide. It will be determined whereby 90% confidence interval for the ratio of averages of measures Cmax and AUC0-inf for IHL-42X and the reference listed drug.

  28 days

• Effect of food on IHL-42X - maximum observed drug concentration

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring Cmax (Maximum observed drug concentration)

  7 days

• Effect of food on IHL-42X - time of the maximum drug concentration

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring Tmax (time of the maximum drug concentration)

  7 days

• Effect of food on IHL-42X - area under the drug concentration time curve from time zero to time of last measurable concentration

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring AUC0-last (Area under the drug concentration-time curve, from time zero to time of last measurable concentration)

  7 days

• Effect of food on IHL-42X - area under the drug concentration time curve from time zero to infinity

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring AUC0-inf (Area under the drug concentration-time curve from time zero to infinity)

  7 days

• Effect of food on IHL-42X - area under the drug concentration time curve from time zero to 12 hours

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring AUC0-12h (Area under the drug concentration-time curve from time zero to 12 hours)

  7 days

• Effect of food on IHL-42X - area under the drug concentration time curve from time zero to 24 hours

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring AUC0-24h (Area under the drug concentration-time curve from time zero to 24 hours)

  7 days

• Effect of food on IHL-42X - the elimination half-life

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring t1/2 (the elimination half-life)

  7 days

• Effect of food on IHL-42X - terminal elimination rate constant

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring kel (Terminal elimination rate constant)

  7 days

• Effect of food on IHL-42X - apparent total body clearance

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring CL/F (Apparent total body clearance)

  7 days

• Effect of food on IHL-42X - apparent volume of distribution

  Assess the effect of food on the uptake and absorption of IHL-42X by measuring Vz/F (Apparent volume of distribution)

  7 days

Secondary Outcomes (1)

• Safety and tolerability

  28 days

Study Arms (4)

Comparator Arm A- Reference Listed Drug/Marinol

ACTIVE COMPARATOR

dronabinol 5 mg, two capsules of 2.5 mg administered on an empty stomach once only in the study period

Drug: Dronabinol 2.5 MG

Comparator Arm B-Reference Listed Drug/Taro Acetazolamide

ACTIVE COMPARATOR

250 mg acetazolamide, one tablet administered on an empty stomach once only in the study period

Drug: Acetazolamide 250 MG

Investigational Product Arm C-IHL42X Fasted

EXPERIMENTAL

IHL-42X (5 mg dronabinol, 250 mg acetazolamide), one capsule administered on an empty stomach once only in the study period

Drug: IHL42X

Investigational Product Arm D-IHL42X Fed

EXPERIMENTAL

IHL-42X (5 mg dronabinol, 250 mg acetazolamide), one capsule administered after food once only in the study period

Drug: IHL42X

Interventions

IHL42X DRUG

IHL-42X consists of acetazolamide and dronabinol.

Also known as: IHL-42X

Investigational Product Arm C-IHL42X Fasted; Investigational Product Arm D-IHL42X Fed

Acetazolamide 250 MG DRUG

A solid tablet containing 250 mg acetazolamide

Also known as: Taro Acetazolamide

Comparator Arm B-Reference Listed Drug/Taro Acetazolamide

Dronabinol 2.5 MG DRUG

A soft gelatin capsules containing 2.5mg dronabinol

Also known as: Marinol

Comparator Arm A- Reference Listed Drug/Marinol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers will be enrolled in the study if they satisfy all the following criteria:
• Ages ≥18 to ≤65 at the time of screening
• BMI ≥18.0 to ≤32.0
• Physically well, in the opinion of the investigator, with no clinically significant psychiatric, cardiac, hepatic, renal, endocrine, gastrointestinal, bleeding, thyroid, cholesterol, or hypertension disorders
• If male, willing to use an approved method of contraception from 30 days prior to dosing, throughout the study, and 90 days after last dose.
• Options include:
• Surgically sterile (vasectomy at least 6 months prior to dosing) Condom + partner with IUD device (in place 3 months prior to dosing through to 90 days after last dose) Condom + partner with diaphragm for at least 30 days prior to dosing through to 90 days after last dose Condom + partner using hormonal contraception for at least 3 months prior to dosing + condom for at least 30 days prior to dosing through to 90 days after last dose OR Contraception not required Sexual partner is surgically sterile. Partner is of non-childbearing potential Same sex relationship Abstinence
• If female of non-childbearing potential, must be postmenopausal with established serum FSH levels \>30IU/L (determined during screening or have undergone one of the following sterilization procedures at least 6 months prior to Visit Day 1;
• Bilateral tubal ligation
• Hysterectomy
• Hysterectomy with unilateral or bilateral oophorectomy
• Bilateral oophorectomy If females of childbearing potential must not be currently pregnant, lactating, or planning to be pregnant and are willing to use an approved method of contraception from 30 days prior to dosing, throughout the study, and 30 days after last dose.
• Options include:
• Condom + IUD device (in place 3 months prior to dosing + 30 days after last dose) Condom + Diaphragm for at least 30 days prior to dosing + 30 days after last dose Condom + Hormonal contraception for at least 3 months prior to dosing + condom for at least 30 days prior to dosing + 30 days after last dose OR Contraception not required Partner has had a vasectomy at least 6 months prior to first dose Of non-childbearing potential (postmenopausal or surgically sterile by any method for at least 3 months prior to check-in) Abstinence Same sex relationship
• Voluntarily consent to participate in the study and complete all study required tasks, as instructed by the protocol, including the completion of questionnaires.

You may not qualify if:

• 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.
• History of cardiac disease or arrythmias
• History of significant psychiatric illness (defined as hospitalisation or history of pharmacological prescription for psychiatric conditions), suicidal ideation, or suicidal attempts
• Current use of illicit drugs or as defined by a positive urine drug test at screening or baseline
• History of alcohol abuse or excessive alcohol intake according to the Australian guidelines (more than 10 standard drinks per week/4 standard drinks per day on average) or alcohol consumption (by self-declaration) defined as \> 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit, or a 125 mL glass of wine).
• Any cannabis use within 30 days of screening
• Known hypersensitivity and/or intolerance to any cannabis products with previous use
• Known hypersensitivity and/or intolerance to sesame oil (dronabinol is formulated in sesame oil)
• Known hypersensitivity and/or intolerance to acetazolamide
• Has taken any vitamins, herbal remedies, supplements or cannabidiol products within 7 days of each check-in
• GAD-7 score of ≥15, MDI score ≥31 OR 3 core symptoms and 5 accompanying symptoms, C-SSRS score ≥4 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 (including meat, dairy products) (As described in FDA guidance for BA and BE studies (Appendix 6))
• Hepatic or renal impairment or disease, as defined as AST/ALT \>1.5 x ULN, eGFR \<60 at screening and check-in.
• History of gastrointestinal disorders or previous surgeries which may impact absorption, distribution, metabolism and/or excretion of the IP (such as cholecystitis, cholecystectomy)
• Female participants who are pregnant, lactating or planning to become pregnant

Sponsors & Collaborators

• Incannex Healthcare Ltd: lead

Study Sites (4)

CMAX

Adelaide, South Australia, 5000, Australia

Location

Nucleus Network Pty Ltd

Geelong, Victoria, 3220, Australia

Location

Nucleus Network Pty Ltd [Commercial Road]

Melbourne, Victoria, 3004, Australia

Location

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Acetazolamide; Dronabinol

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cannabinoids; Terpenes; Hydrocarbons

Study Officials

• Emir Redzepagic, MBBS

  CMAX Clinical Research

  PRINCIPAL INVESTIGATOR

• Phillip Ryan, MBBS

  Nucleus Network Pty Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: May 12, 2023
• Study Start: September 8, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: January 17, 2025

Record last verified: 2024-11

Locations

AU (4)