A Dose-ranging Study to Examine the Pharmacokinetics, Safety, Tolerability and Efficacy of Cybis™ 10:25 THC:CBD Oil in Adults With Chronic Back/Neck Pain
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- Number (and percentage) of participants with one or more serious adverse events
研究概览
简要总结
This is a non-randomised, single arm, open-label study of medical cannabis, Cybis™ 10:25, in participants with chronic back or neck pain in which participants receive escalating doses of Cybis™ 10:25.
详细描述
This is a non-randomised, single arm, open-label study of Cybis™ 10:25 in participants with chronic back or neck pain in which participants receive escalating doses of Cybis™ 10:25.
The purpose of the study is to demonstrate the safety and tolerability of Cybis™ 10:25 in participants with moderate to severe chronic back or neck pain that is unresponsive to over-the-counter non-opioid analgesics.
Participants will undergo a screening visit, then seven clinic visits (Day 1, 2, 8, 15, 22, 29, and 35). Cybis™ 10:25 will be administered oromucosally at doses varying from 0.5 mL once daily to 1.5 mL twice daily. Total duration of dosing is 28 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Aged over 18 years and less than 75 years of age on the date of the Screening Visit;
- •Have back and or neck pain of at least three months duration;
- •Have an average back or neck pain score of between 5 and 9 on a 10-point visual analogue pain scale;
- •Have failed to achieve self-reported satisfactory pain relief using over-the-counter paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs);
- •Are willing to cease all current pain medications 14 days prior to commencing Cybis™ 10:25, and for the duration of the study (except as allowed under rescue medication); Note: Pain medication may include opioids (including but not limited to paracetamol+codeine combinations, codeine, tramadol, tapentadol, buprenorphine), NSAIDs and other co-analgesic medications (such as anti-epileptics, antidepressants, clonidine) and/or any other pain medications.
- •Agree to cease any dietary or herbal supplements (e.g. St John's Wort) fourteen days prior to commencing Cybis™ 10:25, and for the duration of the study;
- •Are willing to cease driving a car or operating heavy machinery from the day of first dosing to seven days after administration of the last dose of Cybis™ 10:25;
- •Agree to use contraception throughout the study, and for one month after the last dose of Cybis™ 10:25 is administered (if reproductive age female) or three months after the last dose of Cybis™ 10:25 is administered (if male); Note: women of childbearing potential must have a negative serum or urine pregnancy test prior to entry into the study. For women, adequate contraception is a double barrier method for the duration of the study and for 30 days post the last study dose. For men, barrier contraception is required for the duration of the study and for 3 months after the last study dose.
- •Agree to adhere to the study protocol; and
- •Are willing and able to provide written informed consent.
排除标准
- •Are pregnant or breastfeeding;
- •Currently using marijuana or other medicinal cannabis products; Use of medical cannabis products > 6 months prior to Screening is acceptable;
- •History of cannabis use disorder (score of 8 or higher on The Cannabis Use Disorder Identification Test - Revised (CUDIT-R);
- •Current or previous allergies or allergic responses to any of the components of the study treatment (e.g., THC, CBD, MCT);
- •Current or previous allergies or allergic responses to any of the components of the rescue medication (e.g. paracetamol, ibuprofen, aspirin, other NSAIDs);
- •Significant cardiac disease (e.g. poorly controlled hypertension, symptomatic ischaemic heart disease, symptomatic heart failure);
- •Chronic liver disease with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper level or normal limits;
- •Chronic renal impairment with eGFR <30mL/min;
- •Taking sildenafil or other PDE5 inhibitors;
- •Being treated with known inducers/inhibitors of CYP3A4, in particular clarithromycin, rifampicin, azole antifungals, antiretroviral agents, anticonvulsants (phenytoin, carbamazepine), SSRI within 30 days of study commencement; Use of such enzyme-altering agents is prohibited throughout the study.
- •Have a major psychiatric disorder (e.g. schizophrenia, psychosis, bipolar disorder, but not anxiety or depression), by history or examination;
- •Are currently using any illicit drug (including, but not limited to, amphetamines, cocaine);
- •Have a history of other substance abuse disorder (as defined by DSM-5);
- •Have active substance abuse disorder (alcohol, illicit drugs);
- •Other clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, or vital signs, which in the opinion of the Investigator, may put the participant at risk of adverse events;
- •Other chronic disease (other than chronic pain) that in the opinion of the Investigator may impact the safety, efficacy and/or pharmacokinetics of the study drug;
- •Are currently participating in, or have participated (in the last 30 days) in a drug or device clinical trial;
- •Currently using opioids (including but not limited to paracetamol+codeine combinations, codeine, tramadol, tapentadol, buprenorphine) and not willing to cease opioids for the duration of the study;
- •COVID-19 vaccination within two (2) weeks of study assessments:
- •Study assessments should not commence until two (2) weeks after a COVID-19 vaccination dose (first, second or booster dose)
- •Subsequent COVID-19 vaccination doses (first, second or booster dose) should not be administered until 7 days after Day 35 study assessments have been completed.
- •Back and/or neck surgery within three (3) months of Screening; or
- •Have history of metastatic cancer or are currently receiving treatment for cancer.
结局指标
主要结局
Number (and percentage) of participants with one or more serious adverse events
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants who drop-out
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants with one or more adverse event of special interest
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants with changes in vital signs
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants who withdraw due to adverse events
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants with one or more adverse event
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants with clinically relevant changes in clinical chemistry
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Adverse events, adverse events of special interest, serious adverse events will be summarised descriptively with the number of participants experiencing the event and the percentages of participants experiencing the event.
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
Number (and percentage) of participants with clinically relevant changes in physical examination
时间窗: Safety and tolerability will be assessed throughout the trial. Up to 35 days.
To assess the safety and tolerability of Cybis™ 10:25 at low (0.5 mL qd), medium-low (0.5 mL bd), medium (1.0 mL bd) and high (1.5 mL bd) doses.
次要结局
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. Time to maximum concentration (tmax) of THC in plasma.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate rescue medication use in participants prescribed Cybis™ 10:25 (proportion of patients requiring rescue medication, the number of doses of rescue medication required, the time to rescue medication).(Day 1, 8, 15, 22, 29 and 35)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. Peak plasma concentration (Cmax) of THC in plasma.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. Area under the concentration/time curve (AUC) will be calculated for THC.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. Time to maximum concentration (tmax) of CBD in plasma.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. The elimination half-life (t1/2) will be calculated for CBD.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate the dose-response relationship between Cybis™ 10:25 and pain response, as measured by the change from baseline in Numerical Pain Rating Scale (NPRS)(Baseline (pre-dose), Day 1, 8, 15, 22, 29 and 35)
- To investigate the dose-response relationship between Cybis™ 10:25 and quality of life as measured by the change from baseline in Medical Outcomes Sleep Survey.(Baseline (pre-dose), Day 1, 8, 15, 22, 29 and 35)
- To investigate the dose-response relationship between Cybis™ 10:25 and pain response, as measured by the change from baseline in Brief Pain Inventory - Short Form.(Baseline (pre-dose), Day 1, 8, 15, 22, 29 and 35)
- To investigate the dose-response relationship between Cybis™ 10:25 and quality of life as measured by the change from baseline in Depression Anxiety Stress Scale.(Baseline (pre-dose), Day 1, 8, 15, 22, 29 and 35)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. The elimination half-life (t1/2) will be calculated for THC.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate the dose-response relationship between Cybis™ 10:25 and quality of life as measured by the change from baseline in Self-Assessment of Treatment (SAT-II) scale.(Baseline (pre-dose), Day 1, 8, 15, 22, 29 and 35)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. Peak plasma concentration (Cmax) of CBD in plasma.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)
- To investigate the pharmacokinetics of Cybis™ 10:25 in participants with chronic back and neck pain following single and repeated doses. The area under the concentration/time curve (AUC) will be calculated for CBD.(Up to 29 days. Samples collected at baseline 0 (pre-dose), 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12.0, and 24.0 hours post dosing. Day 8, 15, 22 and 29 trough levels.)