Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000898459
Ethics application status
Approved
Date submitted
29/07/2025
Date registered
18/08/2025
Date last updated
18/08/2025
Date data sharing statement initially provided
18/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase 2 Double-blind Placebo-controlled Multicenter Cross-over Study with Titration Period to Evaluate the Efficacy and Safety of IRX211a for the Treatment of Breakthrough Cancer Pain in Opioid Tolerant Patients
Scientific title
Phase 2 Double-blind Placebo-controlled Multicenter Cross-over Study with Titration Period to Evaluate the Efficacy and Safety of IRX211a for the Treatment of Breakthrough Cancer Pain in Opioid Tolerant Patients
Secondary ID [1] 315028 0
IRX211-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breakthrough Cancer Pain 338369 0
Condition category
Condition code
Anaesthesiology 334669 334669 0 0
Pain management
Cancer 334789 334789 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This multicentre phase 2 study investigates the use of IRX211a (dronabinol), an inhaled cannabinoid formulation administered via a pressurized metered dose inhaler (pMDI), for the management of breakthrough cancer pain (BTcP) in patients on stable around-the-clock opioid therapy. The study consists of two main phases following an initial screening and 14-day baseline observation period. During the baseline observation period, participants record the frequency and characteristics of their breakthrough cancer pain (BTcP) episodes while continuing their prescribed background opioid therapy. This includes daily tracking of BTcP episode frequency, background pain intensity (twice daily), and use of any previously prescribed rescue medications. Eligibility for randomization requires experiencing between 1 and 4 BTcP episodes per day on at least 7 of the 14 days.
Part A: Open-Label Titration Phase – This is a dose-finding phase with a maximum duration of 3 weeks, in which approximately 156 eligible participants are enrolled. On Day 0, participants receive their initial IRX211a dose (1 mg; 2 actuations) under medical supervision in-clinic, with up-titration (1 actuation of 0.5mg increase per administration until pain relief is achieved or maximum dose reached) permitted up to a maximum dose of 3.5 mg (7 actuations). Doses are increased based on the patient’s assessment of pain relief and tolerability. Participants continue titration at home with detailed e-diary documentation. An effective individualized dose is defined as the lowest IRX211a dose that provides adequate pain relief with tolerable side effects across two consecutive BTcP episodes. It is administered as needed by the participant over the 3-week period, at least once a day. Participants who cannot identify an effective dose by the end of the 3-week titration period are discontinued.
Part B: Double-Blind, Randomized, Placebo-Controlled, Cross-Over Phase – Participants who establish an effective dose in Part A enter Part B. A short interval (~3 days max) between Part A and Part B is required for participants. Each participant receives 10 numbered pMDI inhalers in a pre-randomized sequence (7 containing active IRX211a and 3 containing matching placebo). Over a period of up to 4 weeks, participants treat one BTcP episode per day using their individualized dose, with study medication administered at least 4 hours after any rescue medication. Pain intensity and relief are recorded before and after each administration at multiple time points (5, 10, 15, 30, and 60 minutes). The 10 BTcP episodes are treated in a cross-over design to assess efficacy and tolerability of IRX211a. Adherence to the intervention in this study is primarily monitored through a detailed electronic diary (e-Diary) system, patient training, and scheduled follow-up visits. Participants are trained at the screening visit on how to accurately use the study medication (IRX211a inhaler) and complete the e-Diary using a web-based interface. Scheduled telehealth or site visits every 7±3 days during both phases allow investigators to assess dosing patterns, e-Diary completeness, adverse events, and protocol adherence. These oversight mechanisms collectively ensure that adherence is tracked in real-time and reviewed regularly throughout the trial.
Intervention code [1] 331626 0
Treatment: Drugs
Comparator / control treatment
The placebo is administered via a pressurized metered dose inhaler (pMDI) that is identical in appearance, packaging, and administration method to the active study drug (IRX211a). Adherence is primarily monitored through a detailed electronic diary (e-Diary) system as in the intervention.
Control group
Placebo

Outcomes
Primary outcome [1] 342340 0
To evaluate the efficacy of IRX211a in treating breakthrough pain episodes in opioid tolerant cancer patients using stable doses of opioid medication. Outcome is for both parts of the study
Timepoint [1] 342340 0
Baseline and 30 minutes post intervention. This is assessed for each BTcP episode treated in both parts of the study
Secondary outcome [1] 450399 0
To evaluate the safety and tolerability of IRX211a in patients with Breakthrough Cancer Pain (BTcP) (Composite Outcome for both parts of the study
Timepoint [1] 450399 0
Baseline, 30 and 60 minutes post intervention. This is assessed for each BTcP episode treated in both parts of the study
Secondary outcome [2] 450400 0
To evaluate the efficacy of IRX211a in changing opioid usage for BTcP management in patients in both parts of the study.
Timepoint [2] 450400 0
From baseline to end of Part A period (maximum 3 weeks) and baseline to end of Part B (maximum 4 weeks), Assessed at every intervention administration (maximum of 3 episodes per day in Part A, daily in part B) from baseline and throughout intervention period (maximum 3 weeks for Part A and maximum 4 weeks for Part B),

Eligibility
Key inclusion criteria
1. Male or female, aged equal or more than 18, at screening.
2. Patients must have a current diagnosis of cancer.
3. Eastern Cooperative Oncology Group (ECOG) status of 0 to 3 (with Principal Investigator discretion based on the participant's ability to reliably use the pMDI).
4. Life expectancy should be longer than 3 months.
5. If currently receiving chemotherapy and/or radiotherapy treatment, patients must be on a stable regimen for at least one month (30 days plus/minus 2 days) prior to screening and the treatment(s) is expected to remain stable thoughout the clinical trial. If any changes to treatment are anticipated, detailed information must be provided and it will be at the Investigator’s discretion if the patient will be deemed eligible for this trial.
6. Participants must experience at least 1 and no more than 4 BTcP* episode(s) per day on at least 7 days of the 14-day baseline observation period (i.e. experience a BTcP episode during a minimum of 50% of the days of the baseline observation period).
*Defined as transitory flare of moderate to severe pain (PI more than or equal to 5/10 on an 11-point numerical rating scale (NRS) as the minimum qualifying intensity for BTcP episodes) that occurs against a background of persistent pain controlled to moderate intensity or less, by the opioid regimen.
7. Background stable pain (mean pain less than or equal to 4/10 on numeric rating scale for more than or equal to 1 week prior to enrollment) and adequately controlled with the use of long-acting oral morphine or oral morphine equivalent (OME).
8. Patients must be opioid-tolerant – taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone/day, at least 8 mg of hydromorphone/day, or an equianalgesic dose of another opioid for relief of chronic pain management.
9. Add-on therapy for pain such as physical therapy, biofeedback therapy, acupuncture therapy or herbal remedies, should remain unchanged throughout the duration of trial; if any changes occur they must be reported to the Investigator immediately.
10. No known history or family history of schizophrenia or other psychotic illness; history or presence of severe personality disorder or other significant psychiatric history or mental illness (in the opinion the Investigator).
11. No known allergic reaction to cannabis products (including THC, CBD, marijuana, and hashish), Marinol® and Epidiolex®;
12. The patient is able to perform deep inhalations with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) to be more than or equal to 70% of predicted value and FEV1/FVC ratio of more than 0.7 at screening.
13. Must not be pregnant, breastfeeding (non-lactating), or planning pregnancy.
14. Female patients must have negative serum hCG pregnancy test at screening and negative urine test a check-in.
15. Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomised at least 6 months prior to the first study drug administration) must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 3 months after the last study drug administration:
a. Simultaneous use of intrauterine contraceptive device without hormone release system placed at least 4 weeks prior to the first study drug administration; or intrauterine contraceptive device with hormone release system placed at least 12 weeks prior to first study drug administration; or oral hormonal contraceptives (minimum 12 week use without issue), and a condom for the male partner. Other hormonal contraceptives such as depot are allowed.
16. Females of non-childbearing potential must be:
a. Post-menopausal (absence of menses for at least 12 months prior to the first study drug administration) with confirmation of the post menopausal status by documented FSH level more than or equal to 40 mIU/mL; or
b. Surgically sterile (complete hysterectomy, bilateral oophorectomy or tubal ligation at least 3 months prior to the first study drug administration).
17. All male participants (including men who have had a vasectomy) must agree to use a condom from the first dose and for 90 days after the last dose.
18. Male Patients who are not vasectomised for at least 3 months prior to dosing and who are sexually active with a female partner of childbearing potential must be willing to use one of the following acceptable contraceptive methods from the first dose and for 90 days after the last dose:
a. Simultaneous use of condom and established use of oral, injected or implanted hormonal contraceptive or placement of intrauterine device (IUD) or intrauterine system (IUS) for the female partner;
19. Male patients must be willing not to donate sperm for 90 days after the last dose.
20. Willing and able to adhere to all study requirements, including willingness to remain in the study unit for the entire duration of the confinement period.
21. Able to collect the required Pain Intensity and Pain Relief scores at the appropriate time points for at least 3 BTcP episodes during the screening period.
22. Able to understand the study procedures and provide signed and dated patient informed consent form (ICF) to participate in the study prior to screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of any clinically significant cardiopulmonary disease, including but not limited to moderate to severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stages 2-4 requiring daily use of bronchodilators or steroids), Congestive Heart Failure (NYHA Class III or IV), significant Coronary Artery Disease (CAD) (previous myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention within the last 6 months), Pulmonary Hypertension (mean pulmonary artery pressure more than or equal to 25 mmHg at rest or more than or equal to 30 mmHg during exercise), or uncontrolled symptomatic arrhythmias (such as atrial fibrillation with rapid ventricular response or ventricular tachycardia), or any other condition which, in the opinion of the Investigator, would jeopardize participant safety or impact the validity of study results.
2. History (1 month prior screening) or presence of active unstable lung disease (e.g. asthma, chronic obstructive pulmonary disease [COPD], pulmonary fibrosis, hemoptysis, bronchiectasis) or prior intubation for respiratory illness, as per Investigator discretion. Patients with active infective exacerbation will be excluded.
3. Neurologic or psychological disease that would compromise data collection. This includes patients with cognitive impairment as determined by a Short Blessed Test score >10 or those with acute delirium within 30 days prior to screening.
4. Any laboratory test results deemed clinically significant by the Investigator.
5. Patients with uncontrolled or rapidly escalating pain as determined by the Investigator.
6. Patients with a score more than or equal to 10 Columbia Suicide Severity Rating Scale (C-SSRS)
7. The patient is expected to have surgery during the study.
8. Known allergic reactions to any excipient in the formulations
9. History of substance use disorder, as defined by DSM-5 criteria, such as cocaine, phencyclidine (PCP), cannabis, crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening.
10. Use of marijuana within 1 month prior to the screening.
11. Current (less than 1 year) alcohol as identified during screening in accordance with Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria.
12. Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis:
a. Monoamine oxidase inhibitors (MAOIs) within 14 days prior to dosing;
b. Marinol®, Sativex, Epidiolex® or Medical Cannabis therapy
c. Any investigational drug (non-approved) within the previous 30 days or during the course of the study.
13. Any reason which, in the opinion of the Investigator, would prevent the patient from participating in the study.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple central randomisation by computer that is stratified by sites
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2025
Actual
Date of last participant enrolment
Anticipated
31/08/2026
Actual
Date of last data collection
Anticipated
9/11/2026
Actual
Sample size
Target
156
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 319592 0
Commercial sector/Industry
Name [1] 319592 0
InhaleRx Ltd.
Country [1] 319592 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
InhaleRx Ltd.
Address
Country
Australia
Secondary sponsor category [1] 322093 0
None
Name [1] 322093 0
Address [1] 322093 0
Country [1] 322093 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318155 0
Bellberry Human Research Ethics Committee F
Ethics committee address [1] 318155 0
Ethics committee country [1] 318155 0
Australia
Date submitted for ethics approval [1] 318155 0
10/09/2024
Approval date [1] 318155 0
14/11/2024
Ethics approval number [1] 318155 0

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

Contacts
Principal investigator
Name 143290 0
Dr Arul Sivanesan
Address 143290 0
Vitalis Clinical Research, 456 St Kilda Rd, Melbourne VIC 3004
Country 143290 0
Australia
Phone 143290 0
+610422156206
Fax 143290 0
Email 143290 0
[email protected]
Contact person for public queries
Name 143291 0
Darryl Davies
Address 143291 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 143291 0
Australia
Phone 143291 0
+61 1300633226
Fax 143291 0
Email 143291 0
[email protected]
Contact person for scientific queries
Name 143292 0
Darryl Davies
Address 143292 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 143292 0
Australia
Phone 143292 0
+61 1300633226
Fax 143292 0
Email 143292 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.