Not Yet RecruitingPhase 3ACTRN12621001302842

NanaBis™ an Oro-Buccal Administered delta9-Tetrahydrocannabinol (d9-THC) and Cannabidiol (CBD) Medicine For The Management of Chronic Pain From Metastatic Bone Cancer

NanaBis™ an Oro-Buccal Administered Equimolar d9-THC and CBD Formulation As Monotherapy For The Management of Opioid-Requiring Chronic-Pain Due To Metastatic Cancer: A Phase 3 Multi-Centre, Double Blind, Randomized-Withdrawal Active And Placebo Controlled Clinical Study

Sponsor

Medlab Clinical Ltd

Enrollment

360 participants

Start Date

Oct 1, 2023

Study Type

Interventional

Conditions

Bone Metastases Cancer Pain Management

Summary

The purpose of this study is to determine whether a nanoparticle cannabis-based medicine (NanaBis™) is effective in reducing metastatic bone pain in patients with cancer. Who is it for? You may be eligible for this study if you are aged between 18-75 years old, have been diagnosed with any cancer that has metastasised to bone, and are experiencing bone pain. Study details Participants will be randomised using a computer software program to receive either the NanaBis™ spray and placebo oxycodone tablets for breakthrough pain, a placebo spray and oxycodone tablets or a placebo spray and placebo tablets. Participants will self-administer the spray into their mouth up to 2-7 times every 4 hours unless asleep, and the tablet up to twice per day as needed. All participants will answer a number of questionnaires before the study starts and throughout the study. These questionnaires are answered weekly during the visits to the study site, except for the Numerical Pain Rating Scale which is completed twice daily as part of the participants medication diary. All questionnaires are also completed at the end of the 6-week period. Participants will also have the option to continue the treatment for a further 12 weeks after the study is complete. It is hoped that this study may demonstrate that NanaBis™ is safe, tolerable, and effective at reducing metastatic bone pain in patients with cancer.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 75 Yearss

Inclusion Criteria13

At Screening Phase participants must fulfill all of the following criteria:
i. Prospective male and female participants that are
a. in the age range 18 to 65 years or
b. 65 to 75 years without significant co-morbidities (heart, lung, liver or renal failure, myocardial infarction, cerebral vascular accident, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, connective tissue disease or diabetes mellitus with end-organ damage)
ii. Metastatic bone pain from a cancer diagnosis is the only major cause of pain.
iii. Pathology (imaging) confirmed metastatic bone cancer;
iv. Meet International Classification of Diseases, Tenth Revision (ICD-10) codes for pain management criteria (i.e., bone cancer pain);
v. During the screening period, the participant is on stable opioid pain management and pain severity (NPRS) is less than or equal to 8 with a maximum variation of plus or minus 1.
vi. Pain Detect score is greater than 18
vii. Participant willing and able to provide informed consent and follow study procedures
a. including agreeing to not drive or operate heavy machinery; and
b. females of child-bearing potential agree to use reliable contraception during the duration of the clinical trial;
viii. Patient deemed tolerable to Oxycodone and NanaBis™ determined by medical history of allergies to cannabinoids or opioids

Exclusion Criteria10

i. History of epilepsy or recurrent seizures;
ii. Moderate to severe medical conditions such as
a. Severe hepatic, cardiovascular, pulmonary or renal impairment; or
b. Psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced psychosis, severe mood disorders), that would be assessed at the medical screen;
iii. If patients have been diagnosed with a substance abuse disorder.
iv. Women who are pregnant, lactating or planning to become pregnant;
v. Identified concerns by the nursing / medical team relevant to the safe storage of medications (i.e., NanaBis™ or standard medical therapy);
vi. Participants who may not be available for follow up (i.e., planned or expected travel or other);
vii. Participants plan to undergo any treatment that will substantially reduce the burden of disease (and therefore bone pain) during the screening, titration or maintenance phase of the clinical trial such as radiotherapy or cytotoxic chemotherapy;
viii. Participants who are unable to withhold all analgesia (apart from that which is part of this trial) during the titration and maintenance phase of the study, including bisphosphonates. Medications such as bisphosphonates may be coordinated so they are given either side of the excluded period that covers the titration and maintenance phases

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Interventions

NanaBis™ is a nanoparticle water soluble equimolar solution of d9-THC and CBD administered through the oro-buccal membrane. One dose is equivalent to 2 actuations of the pump delivering 280 µL volume containing 2.5 mg d9-THC and 2.5 mg CBD. The dose administered will be 2-3.5 doses (2 sprays to 7 sprays) per 4 hours unless asleep. To avoid and adapt participants to potential adverse effects of NanaBis™, NanaBis™ will be started at a low dose, which will be gradually escalated. The titration phase that involves cessation of pre-trial analgesia will only commence once NanaBis™ has reached expected therapeutic levels. The dose of sprays and tablets will be transiently or permanently reduced as required to alleviate adverse reactions. The study consists of: - Screening - Pre-Titration (1 Week) - Titration (1 Week) - Maintenance (4 Weeks) - Open Label Extension (12 Weeks) The medicine will be accounted for by the Research Site’s Pharmacy (e.g., GenesisCare). The pharmacy will be responsible for stock management, dispensing and control of all of the investigational drug vials as well as ensure drug storage and environmental monitoring under drug S8 conditions. Participant compliance will be measured from the participant medication diary and exploring the accurate reporting, interpretation verification and validity of the recorded data and that of missing data. This study has three arms: 1. Double-Placebo Arm: Each participant receives both spray-placebo and tablet-placebo. 2. NanaBis™ Treatment Arm: Each participant receives both NanaBis™ and tablet-placebo. 3. Oxycodone Controlled Release (CR) Comparator Arm: Each participant receives both Oxycodone CR and spray-placebo. Oxycodone Controlled Release (CR) used as the comparator will be Oxycontin oral tablets 10 mg – 70 mg twice per day for a duration of 6 weeks. All arms will have Oxycodone Immediate Release (IR) available as required and not limited by the study, except that excessive use in the MAINTENANCE Phase will lead to forced discontinuation. Participants will be allowed 3 days to transition off their prior analgesia at the start of the TITRATION phase. The amount of Oxycodone IR used and the time require to transition off the prior analgesia (0-3 days) will be determined by the treating physician; however, it is recommended that participants showing symptoms or signs of opiate withdrawal be considered for using Oxycodone IR at regular intervals during the TITRATION phase. After the one week TITRATION phase, absence of any opioid withdrawal symptoms will be confirmed with the Subjective Opioid Withdrawal Scale (SOWS). The emergence of opiate withdrawal symptoms due to cessation of all prior analgesics should be prevented by the use of Oxycodone IR; however, to further minimise discontinuations of participants due to opiate withdrawal issues rather than pain control issues, the Double-Placebo Arm will split off the NanaBis™ Treatment Arm after the TITRATION Phase and all participants will be started on either the NanaBis™ Treatment Arm or Oxycodone Controlled Release (CR) Comparator Arm. Best practice for treatment with NanaBis™ is to commence with a sub-therapeutic dose and escalate to a therapeutic dose over a week, which minimises adverse reactions. This study will use a one week PRE-TITRATION SPRAY ADAPTATION phase that will allow escalation of the spray to a therapeutic level before starting the TITRATION phase. If participants have a TITRATION SOWS score greater than 10 points above their START SOWS Score then entry into the MAINTENANCE phase will be postponed until the a TITRATION SOWS score is less than or equal to 10 points above their START SOWS Score. The procedure for down-titration of pre-trial opioid medication will largely be determined at the principal investigator’s discretion, however oxycodone IR as use as breakthrough analgesia is strongly recommended to minimise withdrawal issues, where appropriate. Furthermore, withdrawal issues will be monitored through use of SOWS measure in conjunction with factors such as drowsiness and other opioid-toxicity symptoms with amount of time taken to properly down-titrate the participant also dependant on both baseline duration of opioid treatment and withdrawal response observed, respectively. OPIATE WITHDRAWAL: All participants will have Oxycodone IR available as required for pain and avoidance of opiate withdrawal. Oxycodone IR may need to be prescribed regularly, at least initially, if participants are showing signs or symptoms of opiate withdrawal. Absence of opiate withdrawal will be confirmed with the SOWS before commencing the MAINTENANCE Phase and entry into the MAINTENANCE phase postponed until the a TITRATION SOWS score is less than or equal to 10 points above their START SOWS Score. FORCED DISCONTINUATION: Applies if any of the below criteria are met in any consecutive 3-day period commencing on or after day 10 of the TITRATION period: (i) Pain severity (NPRS) is greater than 5 (ii) Breakthrough Oxycodone is greater than 1/6 of the SCREENING period’s equivalent average daily opioid use and greater than 20 mg /day Oxycodone. DEFINITIONS: • Responder: Participate fulfilling all following criteria: (i) Average pain score (NPRS) less than or equal to 5 (ii) Average breakthrough Oxycodone used is less than or equal to 1/6 of the SCREENING period equivalent average daily opioid use or 20 mg of Oxycodone (whichever is greater). (iii) No discontinuation for efficacy or tolerability reasons. OPEN LABEL EXTENSION (12 weeks): • While there is no evidence during the trial to contradict current data that NanaBis™ is safe and tolerable, open label extension of NanaBis™ will be offered to all participants. • Other analgesics such as pre-trial analgesics to be used as required. • A three day randomised withdrawal study will occur at the end of the 12 week extension, with a 1:1 randomisation of participants to NanaBis™ or Spray Placebo and stable maintenance of all other analgesia. Pain relapse will be determined by a 30% increase in the NPRS score or a greater than 50% increase in breakthrough analgesia use over the three day period.