NanaBis™ an Oro-buccal Administered delta9-Tetrahydrocannabinol (d9-THC) & Cannabidiol (CBD) Medicine for the Management of Bone Pain From Metastatic Cancers

Medlab Clinical

Status and phase: Not yet enrolling; Phase 3

Conditions: Cancer Related Pain

Treatments: Drug: Placebo Spray; Drug: Placebo Tablet; Drug: Oxycodone CR; Drug: Oxycodone IR; Drug: NanaBis™

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04808531

MDC-NB-P3-01

Details and patient eligibility

About

This is a multi-centre, long term, double blind, clinical protocol for NanaBis™ as a monotherapy treatment in participants 18-75 years of age with cancer related pain.

Full description

This trial uses an alternative method to demonstrate the analgesic efficacy of NanaBis™ as a monotherapy in cancer participants. Proving analgesic efficacy requires demonstrating that (i) the analgesic is significantly better than placebo and (ii) that the magnitude of the improvement is clinically important. The latter is standardly done by measuring the change in pain levels from a baseline (no analgesia) to the end of a treatment period. A 30% decrease in the Numerical Pain Rating Scale (NPRS) has been correlated with participants reporting a moderate improvement in their pain and this was adopted as the standard method of demonstrating a clinically important magnitude of improvement. In this strategy, the measure of analgesic efficacy is the proportion of participants in the treatment group whose pain is adequately treated (responders). A responder is defined as a patient who completes the treatment phase with an acceptable level of pain (NPRS ≤ 5) and without requiring excessive amounts of rescue (breakthrough analgesia) medication. Unlimited breakthrough analgesia (Oxycodone) is allowed throughout the study; however, excessive use will result in discontinuation. Comparison of the proportion of responders in the NanaBis™ arm and placebo arms will determine if NanaBis™ is significantly better than placebo. Demonstrating that the proportion of responders in the NanaBis™ arm is non-inferior to the Oxycodone controlled release (CR) comparator arm will determine if the magnitude of improvement (provided by NanaBis™) is clinically important because Oxycodone CR has been established as the benchmark analgesic that provides a clinically important effect.

Enrollment: 360 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

At Screening Phase

Participants must fulfil all of the following criteria:

• Prospective male and female participants that are:

  1. in the age range 18-65 years or
  2. 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)

• Metastatic bone pain from a cancer diagnosis is the only major cause of pain.

• Documented proof (imaging) confirming the Metastatic Bone Disease at the current site of pain and that there has no been treatment since diagnosis

• Meet International Classification of Diseases, Tenth Revision (ICD-10) codes for pain management criteria (i.e., bone cancer pain)

• During the screening period, the participant is on stable opioid pain management and pain severity (NPRS) ≤ 8 with a maximum variation of ± 1

• Pain Detect score > 18

• Participant willing and able to provide informed consent and follow study procedures

  1. including agreeing to not drive or operate heavy machinery; and
  2. females of child-bearing potential agree to use reliable contraception during the duration of the clinical trial

• Patient deemed tolerable to Oxycodone and NanaBis™ determined by medical history of allergies to cannabinoids or opioids

• Patient must not be a participant in a clinical trial or study.

Exclusion criteria

At Screening Phase

Participants will be excluded if they meet any of the following criteria that include:

• History of epilepsy or recurrent seizures

• Moderate to severe medical conditions such as

  1. Severe hepatic, cardiovascular, pulmonary or renal impairment or
  2. Psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced psychosis, severe mood disorders), that would be assessed at the medical screen

• If participants have been diagnosed with a current substance abuse disorder

• Women who are pregnant, lactating or planning to become pregnant

• Identified concerns by the nursing / medical team relevant to the safe storage of medications (i.e., NanaBis™ or standard medical therapy)

• Participants who may not be available for follow up (i.e., planned or expected travel or other)

• 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

• Participants who are unable to withhold all analgesia (apart from which is part of this trial) during the titration and maintenance phase of the study, including bisphosphonates, or are currently exceeding equivalence of 70mg BD Oxycodone CR. Medications such as bisphosphonates may be coordinated so they are given either side of the excluded period that covers the titration and maintenance phases

• Participants will NOT be excluded if they are being treated with maintenance pharmacotherapy to prevent progression of disease such as steroids and hormone therapy, which may be continued during the trial at a stable dose

• Participant will be excluded if they are participating in any other clinical trial or study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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360 participants in 3 patient groups, including a placebo group

Double Placebo Arm

Placebo Comparator group

Description:

Spray Placebo + Tablet Placebo Spray Placebo is a nanoparticle water soluble solution without cannabinoids containing a small amount of hemp seed oil (for fragrance purposes only) as defined by Australian Office of Drug Control (ODC) (https://www.odc.gov.au/hemp-products). One dose is equivalent to 2 actuations of the pump delivering 280 µL volume. Tablet Placebo will be identical to the Oxycontin tablets.

Treatment:

Drug: Placebo Tablet

Drug: Oxycodone IR

Drug: Placebo Spray

Treatment NanaBis™ Arm

Experimental group

Description:

NanaBis™ + Tablet Placebo NanaBis™ is a nanoparticle water soluble equimolar solution of d9-THC and CBD. 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 1 - 3.5 doses (2 sprays to 7 sprays) per 4 hours unless asleep.

Treatment:

Drug: Placebo Tablet

Drug: Oxycodone IR

Drug: NanaBis™

Comparator (Oxycodone) Arm

Active Comparator group

Description:

Spray Placebo + Oxycodone CR Spray Placebo is a nanoparticle water soluble solution without cannabinoids containing a small amount of hemp seed oil (for fragrance purposes only) as defined by Australian ODC (https://www.odc.gov.au/hemp-products). One dose is equivalent to 2 actuations of the pump delivering 280 µL volume. Oxycodone controlled release (CR) used as a comparator will be Oxycontin tablets 10 mg - 70 mg po bd.

Treatment:

Drug: Oxycodone IR

Drug: Oxycodone CR

Drug: Placebo Spray