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

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ClinicalTrials.gov Identifier: NCT04808531
Recruitment Status : Not yet recruiting
First Posted : March 22, 2021
Last Update Posted : March 22, 2021
Sponsor:
Collaborators:
George Clinical Pty Ltd
WriteSource Medical Pty Ltd
Information provided by (Responsible Party):
Medlab Clinical

Brief Summary:
This is a multi-centre, long term, double blind, clinical protocol for NanaBis™ as a monotherapy treatment in participants 18-70 years of age with cancer related pain.

Condition or disease Intervention/treatment Phase
Cancer Related Pain Drug: NanaBis™ Drug: Oxycodone CR Drug: Placebo Spray Drug: Placebo Tablet Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple blinding
Primary Purpose: Treatment
Official Title: NanaBis™ an Oro-buccal Administered Equimolar d9-THC & CBD Formulation as Monotherapy for Management of Opioid Requiring Bone Pain Due to Metastatic Cancer: Phase 3 Multi Centre Blinded Randomized Withdrawal Active & Placebo Controlled Trial
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Double Placebo Arm

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.

Drug: Placebo Spray
Placebo comparator used against both NanaBis™ and Oxycodone depending on randomisation of arms.
Other Name: NanoCelle® Placebo Spray

Drug: Placebo Tablet
Placebo comparator used against both NanaBis™ and Oxycodone depending on randomisation of arms.

Experimental: Treatment NanaBis™ Arm
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 2 - 3 doses per 4 hours unless asleep.
Drug: NanaBis™
NanaBis™ is a nanoparticle water soluble equimolar solution of d9-THC & 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
Other Names:
  • MDCNB-01
  • NanoCelle® d9-THC & CBD

Drug: Placebo Tablet
Placebo comparator used against both NanaBis™ and Oxycodone depending on randomisation of arms.

Active Comparator: Comparator (Oxycodone) Arm

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.

Drug: Oxycodone CR
Oxycodone CR tablet is an opioid agonist supplied in 10 mg, 15 mg, 20 mg, 30 mg,40 mg, 60 mg and 80 mg tablets for oral administration. The tablet strengths describe the amount of oxycodone per tablet as the hydrochloride salt.
Other Names:
  • OxyNorm®
  • OxyContin®
  • Endone®
  • Proladone®
  • Targin®

Drug: Placebo Spray
Placebo comparator used against both NanaBis™ and Oxycodone depending on randomisation of arms.
Other Name: NanoCelle® Placebo Spray




Primary Outcome Measures :
  1. Significant changes in responders with NanaBis™ spray over placebo (p<0.05) [ Time Frame: 6 weeks ]
    To demonstrate that at the end of the 6-week study period the proportion of responders in the NanaBis™ group shows significant change than the proportion of responders in the placebo group

  2. Comparable efficacy in proportion of responders from NanaBis™ spray to the proportion of responders to Oxycodone CR [ Time Frame: 6 weeks ]
    To demonstrate that at the end of the 6-week study period the proportion of responders in the NanaBis™ group is similar to the proportion of responders in the Oxycodone group


Secondary Outcome Measures :
  1. Significant change in the Health-Related Quality of Life Scores Form (36) Health Survey (SF-36) with NanaBis™ spray over placebo (p<0.05) and comparable to Oxycodone CR [ Time Frame: 6 weeks ]

    To demonstrate that at the end of the 6-week study period the Health-Related Quality of Life scores in the Scores Form (36) Health Survey (SF-36) for the NanaBis™ group are significantly changed than in the Placebo group and is similar to the Oxycodone group.

    Change in the Health Survey Scores Form (SF-36) at End of Titration and Optimal Dose Period [Time Frame: Baseline; End of Week 3 (3 weeks)]; and at End of Treatment Period [Time Frame: Baseline; End of Week 6 (3 weeks)]; and at End of Compassionate Period [Time Frame: Baseline; End of Week 18 (12 weeks)]

    The Scores Form 36 (SF-36) includes 8 aspects, (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant scores. Higher scores indicate improvement in health. Domain scale scores 0 (negative health) to 100 (positive health). 100 represents the best health state.


  2. Significant change in the painDETECT score with NanaBis™ spray over placebo (p<0.05) and comparable to Oxycodone CR [ Time Frame: 18 weeks ]

    painDETECT Assessment at Baseline [Time Frame: Baseline]. painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component.

    painDETECT Assessment for Participants at End of Titration and Optimal Dose Period [Time Frame: End of Week 1 to 3]; painDETECT Assessment for Participants at End of the Treatment Period [Time Frame: End of Weeks 4 to 6]; painDETECT Assessment for Participants at End of the Compassionate Period [Time Frame: End of Weeks 7 to 18].

    painDETECT is a participant completed questionnaire. A total score is calculated. Participants with a score between 0 and 12 are scored as being "negative" (no neuropathic pain component). Value between 19 and 38 as being "positive" (presence of neuropathic component)". Values from 13 to 18 are scored as being "unclear".


  3. NanaBis™ Adverse Events [ Time Frame: 18 weeks ]

    To demonstrate that at the end of the 6-week study period that NanaBis™ is safe and tolerable. The daily use of NanaBis™ oro-buccal spray reduces the severity of Treatment-Emergent Adverse Events (safety and tolerability). [Time Frame: Change from Baseline and Titration and Treatment in UKU-Side Effects Rating Scale for Patients (UKU-SERS-Pat) at Weeks 1 to 3 and 4 to 6.]

    Does the daily use of NanaBis™ oro-buccal spray reduce the severity of Treatment-Emergent Adverse Events (safety and tolerability). [Time Frame: Change during Compassionate Use in UKU-SERS-Pat at Weeks 7 to 18.]

    Changes in validated UKU-SERS-Pat scale range is 0 to 3 for rating the degree of severity (mild, moderate or severe) and a second scale for the investigator that assigns a casual relationship of improbable, possible or probable.


  4. Fifty percent or greater request compassionate extension with NanaBis™ spray [ Time Frame: 12 weeks ]
    To demonstrate that at the end of the 6-week study period that after unblinding, half or more of the NanaBis™ group prefer further treatment with NanaBis™ in the compassionate extension phase



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

At Screening Phase

Participants must fulfil all of the following criteria:

  • Prospective male and female participants in the age range 18-70 years
  • Metastatic bone pain from a cancer diagnosis is the only major cause of pain. Markers of disease progression (e.g. tenderness or unrelieved pain with changes in posture) may need to be randomised
  • Pathology (blood, imaging) confirmed metastatic bone cancer
  • Meet International Classification of Diseases-10 (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

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;
    2. cardiovascular or renal impairment; or
    3. psychiatric disorders (i.e., unstable schizophrenia, recent drug-induced psychosis, severe mood disorders), that would be assessed at the medical screen
  • Presence of substance abuse disorder such as nicotine or alcohol, or other illicit or prescription drug dependence (e.g., opioid dependence), or methadone or buprenorphine treatment for opioid dependence
  • 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)
  • Participant may not be available for follow up (i.e., planned or expected travel or other)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04808531


Contacts
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Contact: Prof. Luis Vitetta +61 8188 0311 ext 106 luis_vitetta@medlab.co
Contact: Dr. Michael Lyon +1 604 777 5500 doctorlyon@me.com

Sponsors and Collaborators
Medlab Clinical
George Clinical Pty Ltd
WriteSource Medical Pty Ltd
Additional Information:
Publications:

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Responsible Party: Medlab Clinical
ClinicalTrials.gov Identifier: NCT04808531    
Other Study ID Numbers: MDC-NB-P3-01
First Posted: March 22, 2021    Key Record Dates
Last Update Posted: March 22, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Medlab Clinical:
Cannabis based medicine
d9-tetrahydrocannabinol
Cannabidiol
Cancer Pain
Cancer Bone Pain
Treatment
Monotherapy
Nanoparticle
Tetrahydrocannabinol
Additional relevant MeSH terms:
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Neoplasm Metastasis
Cancer Pain
Neoplastic Processes
Neoplasms
Pathologic Processes
Pain
Neurologic Manifestations
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents