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

Inclusion Criteria27

• Male or female, aged equal or more than 18, at screening.
• Patients must have a current diagnosis of cancer.
• 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).
• Life expectancy should be longer than 3 months.
• 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.
• 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.
• 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).
• 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.
• 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.
• 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).
• No known allergic reaction to cannabis products (including THC, CBD, marijuana, and hashish), Marinol® and Epidiolex®;
• 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.
• Must not be pregnant, breastfeeding (non-lactating), or planning pregnancy.
• Female patients must have negative serum hCG pregnancy test at screening and negative urine test a check-in.
• 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.
• 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).
• 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.
• 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;
• Male patients must be willing not to donate sperm for 90 days after the last dose.
• 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.
• 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.
• Able to understand the study procedures and provide signed and dated patient informed consent form (ICF) to participate in the study prior to screening.