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Trial registered on ANZCTR


Registration number
ACTRN12623000465651
Ethics application status
Approved
Date submitted
19/01/2023
Date registered
5/05/2023
Date last updated
14/06/2024
Date data sharing statement initially provided
5/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Study of the Pharmacokinetics and Safety of IRX211 in Healthy Volunteers
Scientific title
A Phase 1 Study of the Pharmacokinetics and Safety of IRX211 in Healthy Volunteers.
Secondary ID [1] 308782 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Complex Regional Pain Syndrome 328733 0
Condition category
Condition code
Neurological 325733 325733 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
IRX211 is an inhaled formulation of dronabinol, administered through a pressurised metered dose inhaler, and is being developed for the treatment of patients with Complex Regional Pain Syndrome (CRPS). This Phase I study is a double-blind, randomized, placebo controlled, single ascending dose study in healthy male and female subjects.
The study will investigate the pharmacokinetics (PK), safety and tolerability of single escalating doses of IRX211. The study will enrol up to 4 cohorts of 8 participants. For each dose cohort, participants will be randomized accordingly (3:1) to ensure 6 will receive IRX211 and 2 the placebo. The cohorts will enrol in sequential order depending on when participants join the study. They will enrol in either Cohort 1, 2, 3 or 4 to receive one of four doses of IRX211 or placebo respectively. Intended trial doses will include 0.5mg, 1mg, 2.5mg or 5mg. The first cohort will include the initial dosing of a sentinel group (1 IRX211 and 1 placebo participant). The remaining 6 participants in the cohort (5 IRX211 and 1 placebo) will be dosed if, in the opinion of the investigator or delegate, there are no significant safety concerns identified in the sentinel participants within the first 24 hours after administration of the dose (IRX211 or placebo). The study will dose ascend once safety data and PK data are reviewed by the Safety Review Committee (SRC). The SRC will also advise if sentinel dosing will be required for subsequent cohorts.

Participants will be screened within 28 days prior to dosing. Participants will report to the study site on the day prior to administration of IRX211 to confirm eligibility. Participants will complete at least a 10 hour fast prior to study drug administration. Participants will receive either IRX211 or placebo on Day 1. Participants will be trained to self-administer a single dose of the study drug via the inhaler under close supervision. Participants will remain at the study site for observation through to 8 hours post-dose and will complete an end of study visit 7 ± 2 days after dosing.
Intervention code [1] 325236 0
Treatment: Drugs
Comparator / control treatment
Matching inhalers containing only the excipients (no active drug) will be used as a placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 333591 0
To determine the safety and tolerability of escalating doses of IRX211 administered as a single inhaled dose in healthy volunteers.
Incidence and severity of adverse events (AE);
Incidence of serious adverse events (SAEs) and suspected unexpected serious adverse reactions;
Clinically significant changes from baseline in: Laboratory evaluations (hematology, biochemistry, urinalysis), Electrocardiograms (ECGs), Vital signs.

Examples of known/possible adverse events include:

1. Respiratory problems: Inhaling the drug can cause irritation of the throat, airways and lungs, leading to potential respiratory issues such as cough, wheezing, shortness of breath or infection. A lung function (FEV1%) test will be conducted on a regular basis to evaluate this.

2. Possible haemodynamic effects: such as lower blood pressure, higher heart rate, potential light-headedness and fainting. These are typically mild, and the participants will be monitored for these.

The following assessments will be performed at specific time points throughout the study:

Vital signs measurements will include systolic and diastolic blood pressure (mmHg) measured using a digital sphygmomanometer, radial pulse rate (beats/minute) and respiratory rate (breaths/minute) measured manually, oxygen saturation by pulse oximetry, and body temperature (tympanic; °C) using a digital thermometer.

A 12-lead ECGs will be performed and the following ECG parameters will be assessed: heart rate, PR, QRS, QT, QTcF.

FEV1% will be performed as a screening evaluation. FEV1% is a measure of lung function and is defined as the proportion of a person's forced vital capacity (FVC) that can be expired in the first second of forced expiration. Measurements will be taken electronically by spirometry.

Blood analysis will be performed to assess aspects of biochemistry and haematology.

Urine analysis will be performed to detect effects on the function of the kidney.

A discharge checklist assessing activity, respiration, circulation, consciousness and oxygen saturation) will be completed prior to discharge.

The study will dose ascend once safety data and PK data are reviewed by the Safety Review Committee (SRC).
Timepoint [1] 333591 0
On day -1 (pre-dose), day 1 (dosing), and day 7 (+/-2 days) post-dose.
Secondary outcome [1] 417652 0
To determine the systemic exposure of escalating doses of IRX211 administered as a single inhaled dose in healthy volunteers.
Plasma Pharmacokinetic (PK) parameters relating to the study drug to be assessed include: areas under the plasma concentration curve (AUC), peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination half-life (t1/2), apparent total clearance (CL/F); apparent volume of distribution (Vz/F). Analytes screened will include: Delta-9-Tetrahydrocannabinol (THC) and 11-Hydroxy-Delta-9-Tetrahydrocannabinol (11-Hydroxy-THC).
Timepoint [1] 417652 0
On day 1, plasma samples for Pharmacokinetic (PK) will be collected pre dose, and at 1, 2, 3, 4, 5, 10, 15, 30, 60, 90, 120 and 150 minutes post-dose, at 4, and 8 hours post-dose.

Eligibility
Key inclusion criteria
Each participant must meet all the following criteria to be enrolled in this study:
1. Aged between 18 and 55 years (inclusive at Day 1).
2. Free from clinically significant (in the opinion of the Investigator) illness or disease as determined by their medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory determinations.
3. BMI between 18 and 32 kg/m2 (inclusive) at Screening.
4. Weight greater or equal to 50.0 kg at Screening.
5. Adequate venous access in both arms for collection of a number of blood samples.
6. Capable of understanding the purposes and risks of the study and able to provide written informed consent before any study-specific screening procedures are performed.
7. Willing and able to adhere to all protocol requirements, including willingness to comply with scheduled visits, and tolerance to dosing using an inhaler.
8. The subject is able to perform deep inhalations with FEV1 more than 80%.
9. Female subjects of childbearing potential must be abstinent from heterosexual intercourse or agree to use an acceptable form of contraception with a male sexual partner and agrees to refrain from egg donation.
10. Male subjects must be abstinent from heterosexual intercourse or agree to use an acceptable form of contraception with a female sexual partner of childbearing potential and agrees to refrain from sperm donation.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants who meet any of the following criteria will be excluded from this study:
1. History of coronary disease, peripheral vascular disease, cerebrovascular accident, transient ischemic attack, uncontrolled hypertension or signs/symptoms of ischemic heart disease.
2. History of acute or severe bronchial asthma (excluding childhood or exercise induced asthma), diagnosed obstructive sleep apnea, hypoxia, hypoxemia, hypercarbia, or other obstructive airway disease or any condition that may increase the risk for respiratory depression.
3. History of neurologic conditions such as seizures (excluding single febrile seizures during childhood) or convulsive disorders (including epilepsy), severe head injury or increased intracranial pressure.
4. Any concussion (within 5 weeks from Day 1), or prior concussion where there are ongoing symptoms.
5. Presence of current psychiatric condition or psychiatric condition requiring pharmacological management within the last 6 months, presence of current or history of psychosis/schizophrenia and bipolar disorders.
6. A calculated creatinine clearance of less than 80 mL/minute at Screening or Check-In (Day -1) according to the equation using Cockcroft and Gault.
7. Liver function tests showing values for alanine transaminase (ALT) or aspartate transaminase (AST) greater than 1.5 times the upper limit of normal (ULN) at Screening.
8. Evidence or history of clinically relevant (in the opinion of the Investigator) other cardiovascular, pulmonary, neurologic or renal disorders or hepatic, gastrointestinal, oral (difficulty swallowing / taking oral medication), hematological, endocrine, or psychiatric impairment/disorders, making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study in the opinion of the Investigator.
9. Have undergone surgery requiring or have received (for any reason) anesthetic within 30 days of Day 1.
10. Use of central nervous system (CNS) depressants including opioids, sedatives, anxiolytics, hypnotics, neuroleptics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines or cimetidine within 30 days of Day 1.
11. Use of macrolide antibiotics (e.g., Erythromycin), azole antifungal agents (e.g., Ketoconazole) or protease inhibitors (e.g., Ritonavir) within 30 days of Day 1.
12. Use of any prescription medication within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and the Medical Monitor (in writing). COVID-19 vaccine within 1 week of Day 1 may be administered. Paracetamol ibuprofen, hormonal contraception may be administered.
13. Use of any over the counter product, herbal product, diet aid, or hormone supplement, with a particular regard to hemp or products containing cannabidiol, within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and Medical Monitor (in writing). Vitamins and dietary supplements and topical preparations may be administered (other than those in the prohibited list).
14. History of severe allergic or anaphylactic reactions, known intolerance, allergy or hypersensitivity reactions to dronabinol.
15. Positive screening test for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen or Hepatitis C antibody.
16. Evidence or history of substance or alcohol abuse (drink more than 4 standard units of alcohol per day or greater or equal to 14 standard units per week), including positive results for the urine drugs of abuse test or a positive alcohol breath test at Screening or at Check-In (Day -1).
17. Unwilling or unable to abstain from recreational drug/substance use, alcohol, from 48 hours before check-in until discharge.
18. Unwilling or unable to abstain from caffeine or other xanthine-containing products from check-in until discharge.
19. Subjects who within the last 3 months (from the screening visit) were smokers or vapers.
20. Consumption of grapefruit, grapefruit juice or any products containing CYP3A4 inhibitors and/or inducers and/or CYP2C9 F inhibitors and/or inducers within 14 days of Day 1 and through to completion of the study.
21. Female subject or female partner of male subject that is pregnant or lactating.
22. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 5 half-lives prior to Day 1.
23. Donation or loss of more than 500 mL of blood within 1 month of Day 1 and/or plans to donate blood during the study.
24. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrolment.

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)
Sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
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
Completed
Date of first participant enrolment
Anticipated
9/05/2023
Actual
6/06/2023
Date of last participant enrolment
Anticipated
Actual
24/10/2023
Date of last data collection
Anticipated
Actual
31/10/2023
Sample size
Target
32
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312999 0
Commercial sector/Industry
Name [1] 312999 0
InhaleRx Ltd
Country [1] 312999 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
InhaleRx Ltd
Address
Level 5, 126 Phillip Street, Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 314685 0
None
Name [1] 314685 0
Address [1] 314685 0
Country [1] 314685 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312262 0
Alfred Health - Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 312262 0
Ethics committee country [1] 312262 0
Australia
Date submitted for ethics approval [1] 312262 0
11/01/2023
Approval date [1] 312262 0
16/03/2023
Ethics approval number [1] 312262 0
644/22 (HREC/92177Alfred-2023)

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

Contacts
Principal investigator
Name 124030 0
Dr Phillip Ryan
Address 124030 0
Nucleus Network
Level 5 Burnet Tower, 89 Commercial Rd, Melbourne, VIC 3004
Country 124030 0
Australia
Phone 124030 0
+61 438 009 787
Fax 124030 0
Email 124030 0
p.ryan@nucleusnetwork.com.au
Contact person for public queries
Name 124031 0
Michelle Tusler
Address 124031 0
iNGENu CRO Unit 22, 456 St Kilda Road, Melbourne, VIC 3004
Country 124031 0
Australia
Phone 124031 0
+61 1300 633 226
Fax 124031 0
Email 124031 0
clinicaltrial.queries@ingenucro.com
Contact person for scientific queries
Name 124032 0
Phillip Ryan
Address 124032 0
Nucleus Network
Level 5 Burnet Tower, 89 Commercial Rd, Melbourne, VIC 3004
Country 124032 0
Australia
Phone 124032 0
+61 3 85939800
Fax 124032 0
Email 124032 0
p.ryan@nucleusnetwork.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
Sensitive commercial data


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.