A Randomized Double Blind Placebo Controlled, Proof-of-concept, Crossover Clinical Trial of Vapourized Cannabis in Adults With Painful Osteoarthritis of the Knee
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Total pain reduction of vapourized cannabinoids with varying degrees of THC/CBD ratios in patients with painful OA of the knee.
研究概览
简要总结
Primary Objective:
- To determine the analgesic dose-response characteristics of vapourized cannabinoids with varying degrees of delta-9-tetrahydrocannabiol (THC)/ Cannabidiol (CBD) ratios.
Secondary Objectives:
- To compare functional changes and patient preferences of different cannabinoid (THC, CBD) profiles in patients with OA (Osteoarthritis);
- To describe the Pharmacokinetics (PK) of vapourized cannabis of differing cannabinoid profiles in patients with OA;
- To explore the short term safety of vapourized cannabis with different cannabinoid profiles.
- To describe the incidence and severity of psychoactive events.
详细描述
A Phase IIa randomized double blind placebo controlled crossover trial (RCT) using six different herbal cannabis drug product formulations prepared by the Sponsor, Prairie Plant Systems Inc. An initial screening period (minimum one week) will be completed for pain assessment and determination of eligibility. After screening, eligible subjects will be randomly assigned to receive all 6 different formulations in a random order.
The study will be conducted using six periods of 7 days duration, with each period consisting of one day of exposure and 6 days of washout from study drug. The study will therefore take 6 weeks to be completed for each enrolled subject with an additional week for adverse event monitoring after the final study exposure. Total time in study may therefore be a maximum of nine weeks (including screening).
Adult subjects (age ≥50y) will be recruited with chronic (>3 months) moderate to severe pain (pain score ≥40/100 on visual analogue scale) due to primary osteoarthritis (OA) of the knee as defined by American College of Rheumatology (ACR) criteria. Target enrolment for this study is 36 (18 from each site).
The study will be conducted at the Alan Edwards Pain Management Unit of the McGill University Health Centre, in Montreal, Quebec, Canada and the Pain Management Unit at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, Canada. A dedicated ventilated room is available at these sites for cannabinoid inhalation studies as used in prior evaluation trials on medicinal cannabis.
All subjects meeting eligibility criteria after the screening period will be randomized to receive all 6 herbal cannabis drug product formulations in a randomly assigned order of treatment between Clinical Visit (CV) 2 and CV7.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic (primary) OA of the knee as defined by American College of Rheumatology criteria
- •Age ≥50 years
- •Numerical Rating Scale (NRS) Pain intensity score ≥ 4 (on a 0-10 scale)
- •Stable medication and treatment regimen
- •Open to Canadian Residents only
排除标准
- •Pregnant/nursing
- •BMI >39kg/m2
- •Secondary causes of OA
- •Stage IV OA of the knee
- •Significant other cause of pain (e.g. fibromyalgia, CRPS)
- •Significant cardiac, neurological, psychiatric or respiratory disease
- •Joint infiltration in 30 days prior to trial or during study
- •Positive urine screen for THC
研究组 & 干预措施
CanniMed™ DPF-I Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation (DPF) with a potency specification similar to CanniMed™ 22·1 product, of 21.9% w/w total THC and 0.8% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Cannabis (Drug)
CanniMed™ DPF-I Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation (DPF) with a potency specification similar to CanniMed™ 22·1 product, of 21.9% w/w total THC and 0.8% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Volcano® Medic Vapourizer (Device)
CanniMed™ DPF-II Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification the same as the CanniMed™ 15·5 product, of 15.0% w/w total THC and 5.0% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Cannabis (Drug)
CanniMed™ DPF-II Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification the same as the CanniMed™ 15·5 product, of 15.0% w/w total THC and 5.0% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Volcano® Medic Vapourizer (Device)
CanniMed™ DPF-III Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification the same as CanniMed™ 9·9 product, of 9.0% w/w total THC and 9.5% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Cannabis (Drug)
CanniMed™ DPF-III Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification the same as CanniMed™ 9·9 product, of 9.0% w/w total THC and 9.5% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Volcano® Medic Vapourizer (Device)
CanniMed™ DPF-IV Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification similar to CanniMed™ 4·10 product, of 3.8% w/w total THC and 10.0% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Cannabis (Drug)
CanniMed™ DPF-IV Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification similar to CanniMed™ 4·10 product, of 3.8% w/w total THC and 10.0% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Volcano® Medic Vapourizer (Device)
CanniMed™ DPF-V Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification similar to CanniMed™ 1·13 product profile of 0.6% w/w total THC and 13.0% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Cannabis (Drug)
CanniMed™ DPF-V Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of finely ground herbal cannabis drug product formulation with a potency specification similar to CanniMed™ 1·13 product profile of 0.6% w/w total THC and 13.0% w/w total CBD is vapourized and inhaled by study subjects.
干预措施: Volcano® Medic Vapourizer (Device)
CanniMed™ DPF-P Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of ethanol extracted DPF-V, reducing the potency profile to <0.3% w/w total THC and <0.3% w/w total CBD (comparable to the threshold levels described for "industrial hemp", as per the Canadian Industrial Hemp Regulations (SOR/98-156), is vapourized and inhaled by study subjects.
干预措施: Cannabis (Drug)
CanniMed™ DPF-P Volcano® Vapourization
Using the Volcano® Medic, a dose of 100 mg of ethanol extracted DPF-V, reducing the potency profile to <0.3% w/w total THC and <0.3% w/w total CBD (comparable to the threshold levels described for "industrial hemp", as per the Canadian Industrial Hemp Regulations (SOR/98-156), is vapourized and inhaled by study subjects.
干预措施: Volcano® Medic Vapourizer (Device)
结局指标
主要结局
Total pain reduction of vapourized cannabinoids with varying degrees of THC/CBD ratios in patients with painful OA of the knee.
时间窗: 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes post-dose
The main efficacy endpoint is pain reduction, calculated as a change in pain intensity (VAS pain intensity) following each exposure. A Total Pain Reduction (TOTPAR) score is calculated from repeated VAS pain scores taken immediately before (baseline) and every 15 minutes after exposure for the first hour then half-hourly for the remaining two hours after treatment exposure (treatment). The treatment VAS pain intensity scores are then subtracted from the baseline VAS pain intensity to generate a pain relief score for each time point. The sum of pain relief scores from each time point is used to generate a 3-hour Total Pain Reduction (TOTPAR-3) score for each exposure.
次要结局
- Blood chemistry - renal function(Up to 7 weeks)
- Hematology - hematocrit level (complete blood count)(Up to 7 weeks)
- Pain, stiffness, physical, social and emotional functional outcomes of vapourized cannabis with varying degrees of THC/CBD ratios in patients with painful OA of the knee.(Up to 6 weeks)
- Pharmacokinetics profile of 7 plasma cannabinoid metabolites from vapourized cannabis of differing cannabinoid profiles in patients with OA.(0, 15, 30, 60, 120 and 180 minutes post-dose)
- Changes in blood pressure from baseline(Up to 7 weeks)
- Changes in heart rate (HR) from baseline(Up to 7 weeks)
- Blood chemistry - liver function(Up to 7 weeks)
- Cannabinoid urine analysis at screening and for washout confirmation(Up to 7 weeks)
- Psychoactive adverse events(Up to 6 weeks)
- Patient global rating of preference for each cannabis preparation.(Up to 6 weeks)
- Visual Analog Scale (VAS) feelings of drug effect(Up to 6 weeks)