About Phase 3 Trial
NanaBis™ an oro–buccal administered equimolar THC and CBD formulation as monotherapy for the management of opioid-requiring–chronic–pain due to metastatic bone cancer: a phase 3 multi-centre, quadruple-blind, randomized-withdrawal active and placebo-controlled clinical study.
This phase III trial uses a randomized-withdrawal method to demonstrate the analgesic efficacy of NanaBis™ as a monotherapy in cancer participants.
- Demonstrate that at the end of the 6-week study period the proportion of responders in the NanaBis™ treated group is significantly greater than the proportion of responders in the placebo group.
- Denonstrate that at the end of the 6-week study period the proportion of responders in the Oxycodone CR treated group is significantly greater than the proportion of responders in the placebo group (study validation).
- Demonstrate that at the end of the 6-week study period the HR-QoL scores in the NanaBis™ treated group are significantly greater than in the Placebo group and non-inferior to the Oxycodone CR treated group.
- Demonstrate that NanaBis™ is safe and tolerable.
- Demonstrate that half or more of the NanaBis™ treated group preferred further treatment with NanaBis™ in the open label extension study (note that all participants will be offered open label extension if appropriate).
Trial design shown on ClinicalTrials.gov, as of 22nd April 2021
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.
NanaBis™ Study Progression
Phase I/II (SAD/MAD), Royal North Shore Hospital
- NanaBis™ displayed approximately 2x the bioavailability reported for Nabiximols spray (same or higher plasma levels from half the dose).
- NanaBis™ appeared to be more efficiently absorbed across the mucous membrane than reported for Nabiximols (one peak compared to two and faster time to maximum concentration).
Pain reduction and quality of life (QoL) improvements:
- NanaBis™ treatment demonstrated a 12% reduction in pain from baseline for all patients (heterogeneous group; p=0.02).
- Homogeneous group of metastatic bone pain patients (from breast or prostate cancer) groups showed a clinically important 33% reduction in pain severity (p<0.01).
- NanaBis™ treatment showed clinically significant improvement in patient functioning including emotional functioning, fatigue, dyspnoea, insomnia and appetite.
NanaBis™ use and opioid use:
- Cancer patients on NanaBis™ used on average only 6.4 mg/day each of THC and CBD (half the average dose reportedly required for Nabiximols for an equivalent effect in a similar patient group).
- NanaBis™ treatment allowed patients to maintain or decrease opioid use. With progressive disease, there was no increase in opioid use.
- After ceasing NanaBis™ participants required increased opioids to maintain analgesia.
- No serious adverse events were related to NanaBis™ treatment. There were non-serious adverse events in a minority of patient (dizziness, drowsiness, and nausea), which generally did not warrant cessation of NanaBis™ treatment.
- The water-soluble nanoparticle vehicle used in the NanaBis™ spray did not cause irritation at the site of application, unlike reported for the ethanol (50% w/v) vehicle used in Nabiximols spray.
Clarke S BB, McLachlan AJ, Henson JD, Rutolo D, Hall S, Vitetta L. Pilot Clinical and Pharmacokinetic Study of Δ9-Tetrahydrocannabinol (THC) / Cannabidiol (CBD) Nanoparticle Oro-Buccal Spray in Patients with Advanced Cancer Experiencing Uncontrolled Pain. Cancers. 2020; UNDER REVIEW.
NanaBis™ Observational Study Progression
Multiple Australian sites (general and specialty medical practices).
Observational study data from the last review, dated April 2021
- An interim analysis of 119 patients who have completed six and 12-month administration of the drug has shown a 55%^ reduction in pain scores, with significant quality of life improvements also reported in the areas of sleep, mood and general activities.
- It is the fifth monitoring report on the 12-month study and complements results from the earlier Phase I Royal North Shore Hospital pilot study in New South Wales.
- Medlab has recruited almost 40% (or 801 people) of a total 2000 participants into the observational study, ranging in age from 21 years to 99 years with females representing 59% of the intake.
- Approximately 3% of the 801 participants presented with cancer-induced bone pain, with 99% registering chronic pain and 1% with acute pain.
- Preliminary analysis of their Brief Pain Inventory (BPI) scores after six and 12 months showed improvement in mean pain scores from 6.5 at the commencement of the study; to 5.5 at six months; and 4.7 at 12 months.
- Of the 119 patients (65% female; 35% male) who have completed six and 12-month courses of NanaBis™, approximately 50% had muscular or neuropathic pain; 32% had soft tissue pain with muscular pain; 11% had visceral pain; and 7% registered “other categorised pain”.
Safety and Tolerability
The results support the safety and tolerability of NanaBis™ for pain in a chronically ill cohort of patients with intractable pain. Furthermore, the study presented preliminary analgesic efficacy of NanaBis™ for pain management in a real world setting while remains consistent with the growing body of evidence supporting the drug.
^ Results are relative to the 55% of participants that had been tracked as of today’s date.
Study approved by NIIM Human Research Ethics Committee, approval ID 0052E_2019.
About NanaBis™ and NanoCelle®
NanaBis™ is an investigational new product containing a 1:1 ratio of delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in a sub-micron (NanoCelle®) spray applied to the oro-buccal membrane.
Medlab’s proprietary sub-micron delivery system NanoCelle® creates nano-sized water-soluble particles that enable optimised delivery of particles, overcoming issues with solubility and degradation.
NanoCelle® is optimised for buccal absorption, bypassing first-pass metabolism, a digestive mechanism known to significantly degrade compounds via the gastrointestinal route. NanoCelle® allows NanaBis™ to rapidly cross the buccal membrane and utilises the facial lymphatics allowing for a rapid systemic response.
About Cancer Bone Pain & Opioids
Cancer-induced bone pain is a neuropathic pain by medical definition and is degenerative in nature. It impacts about 600,000 new breast and prostate cancer patients in US, Australia and Canada each year. Up to 75% of patients with bone metastasis endure crippling bone pain.
Opioids or opioid derivatives remain the main method of treatment for cancer-related pain. Despite the known side effects of opioids, there’s been little advancement in the management of cancer pain. Abuse and toxicity profiles underpin a need for opioid alternatives.
Urol Clin North Am. 2017 November; 44(4): 611-621