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
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 360
- 主要终点
- Significant changes in responders with NanaBis™ spray over placebo (p<0.05)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple blinding
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At Screening Phase
- •Participants must fulfil all of the following criteria:
- •Prospective male and female participants that are:
- •in the age range 18-65 years or
- •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
- •including agreeing to not drive or operate heavy machinery; and
- •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.
排除标准
- •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
- •Severe hepatic, cardiovascular, pulmonary or renal impairment or
- •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.
研究组 & 干预措施
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.
干预措施: Placebo Spray (Drug)
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.
干预措施: Placebo Tablet (Drug)
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.
干预措施: Oxycodone IR (Drug)
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 1 - 3.5 doses (2 sprays to 7 sprays) per 4 hours unless asleep.
干预措施: NanaBis™ (Drug)
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 1 - 3.5 doses (2 sprays to 7 sprays) per 4 hours unless asleep.
干预措施: Placebo Tablet (Drug)
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 1 - 3.5 doses (2 sprays to 7 sprays) per 4 hours unless asleep.
干预措施: Oxycodone IR (Drug)
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.
干预措施: Oxycodone CR (Drug)
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.
干预措施: Placebo Spray (Drug)
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.
干预措施: Oxycodone IR (Drug)
结局指标
主要结局
Significant changes in responders with NanaBis™ spray over placebo (p<0.05)
时间窗: 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. A responder is defined as a participant who completes the maintenance phase with an acceptable level of pain (NPRS is equal to 5) and without requiring excessive amounts of rescue (breakthrough analgesia) medication. NPRS Assessment \[Time Frame: Baseline and then twice daily for the duration of the study\]. The NPRS questionnaire is completed by the participant to determine their pain intensity. The NPRS is an 11-point scale scored from '0-10'. A score of '0' being no pain and a score of '10' being the most intense pain imaginable. Participants select the value that is most in line with the intensity of pain they have experienced in the last 24 hours.
次要结局
- Significant change in the Health-Related Quality of Life Scores with NanaBis™ spray over placebo (p<0.05) and comparable to Oxycodone CR(6 weeks)
- Comparable efficacy in proportion of responders from NanaBis™ spray to the proportion of responders to Oxycodone CR(6 weeks)
- NanaBis™ Adverse Events(18 weeks)
- Fifty percent or greater of the NanaBis™ treated group request compassionate extension with NanaBis™ spray(12 weeks)
- Significant change in the NPRS score with NanaBis™ spray over placebo (p<0.05) and comparable to Oxycodone CR(18 weeks)