Nabilone for Non-motor Symptoms in Parkinson's Disease: A Randomized Placebo-controlled, Double-blind, Parallel-group, Enriched Enrolment Randomized Withdrawal Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Changes of Non-motor Symptoms
研究概览
简要总结
This is a randomized placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal study assessing the efficacy and safety of nabilone for non-motor symptoms in patients with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the psychoactive component of cannabis. Nabilone acts as a partial agonist on both Cannabinoid 1 (CB1) and Cannabinoid 2 (CB2) receptor in humans and therefore mimics the effect of THC but with more predictable side effects and less euphoria.
Part 1 is an open-label dose adjustment phase of the study. In eligible patients, a screening period is followed by an open-label nabilone dose optimization phase and a stable phase for at least 1 week. Treatment responders will be included in Part 2 of the study (randomized placebo-controlled, double-blind, parallel-grouped).
Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of the study.
详细描述
This is a randomized placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal study assessing the efficacy and safety of nabilone for non-motor symptoms in patients with Parkinson´s Disease. Nabilone is an analogue of tetrahydrocannabinol (THC), the psychoactive component of cannabis. Nabilone acts as a partial agonist on both Cannabinoid 1 (CB1) and Cannabinoid 2 (CB2) receptor in humans and therefore mimics the effect of THC but with more predictable side effects and less euphoria.
Part 1 is the open-label dose adjustment phase of the study. In Part 1, eligible subjects, who have signed the informed consent form at the screening visit, will receive open-label nabilone starting with a dosage of 0.25 mg in the evening. During dose titration and optimization, nabilone will be titrated in 0.25 mg increments (increase by 0.25 mg/ every one to four days) up to a maximum dose of 1 mg twice daily. Patients should be on a stable nabilone dose for at least 1 week afterwards until Baseline Visit (V 0).
Part 2 is the placebo-controlled, double-blind, parallel-group randomized withdrawal phase of the study. At Baseline Visit, treatment responders will be included in Part 2 of the study (randomized placebo-controlled, double-blind, parallel-grouped). Responders are randomized in a 1:1 ratio at Baseline Visit to receive either nabilone or matching placebo for 4 weeks + 2 days. The placebo-controlled, double-blind, randomized withdrawal phase will end with a clinic visit (Termination Visit V 1). Following this, the study medication will be tapered in all patients. During this period the patients will receive phone calls every other day. A Safety Telephone Call and a Safety Follow-Up Visit will be performed.
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
placebo-controlled, double-blind, parallel-group with 1 : 1 randomization
入排标准
- 年龄范围
- 30 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible for the study subjects must meet all inclusion criteria:
- •Age ≥30 years
- •Diagnosis of Parkinson´s Disease (PD): PD should be either de novo or on stable medication without disturbing motor fluctuations or dyskinesia.
- •NMS with a score of ≥4 on MDS-UPDRS Part
- •One of the following domains have to be affected with a score ≥2: 1.4 (anxious mood) or 1.9 (pain)
- •On a stable regimen of anti-parkinson medications for at least 30 days prior to screening and willing to continue the same doses and regimens during study participation
- •Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation
- •Patient is informed and had enough time and opportunity to think about his/her participation in the study and has signed a current Institutional Review Board-approved informed consent form
- •Contraception
- •Women of childbearing potential must use or attest an acceptable method* of contraception starting 4 weeks prior to study drug administration and for a minimum of 1 month after study completion.
- •Men with a potentially fertile partner must be willing to use an acceptable method of contraception for the duration of the study and for 3 months after study drug discontinuation or have had a vasectomy.
排除标准
- •Patients with any of the following characteristics will be excluded from entering the study:
- •Patient previously participated in any study with nabilone.
- •Current use of cannabinoids or use of cannabinoids within 30 days prior to screening.
- •Patient is currently participating in or has participated in another study of investigational products within 30 days prior to screening.
- •Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post stroke).
- •Patient presents with motor complications which are, based on the investigator's judgment, not adequately controlled (i.e. a score ≥2 on one of the items of the MDS-UPDRS Part IV at screening)
- •Hoehn and Yahr stage > 3
- •Evidence of disturbing (i.e. requiring treatment) impulse control disorder in the participant. Can be resolved through a structural interview during screening period.
- •History of neurosurgical intervention for PD
- •presence of symptomatic orthostatic hypotension at screening (MDS-UPDRS 1.12 > 2)
- •Use of prohibited medication (e.g. benzodiazepines (except for clonazepam up to a maximum of 1.5 mg per d), lithium, opioids, buspirone, muscle relaxing agents, central nervous system depressing substances, ...)
- •Patients with laboratory values that are out-of-range at Screening (or within 4 weeks prior to Screening) and haven´t been reviewed and documented as not clinically significant by the investigator. Lab Tests can be repeated for confirmation.
- •Patients with known or newly diagnosed sinus tachycardia in ECG evaluation at Screening or within 4 weeks prior to Screening.
- •presence of an acute or chronic major psychiatric disorder (e.g., Major Depressive Disorder, psychosis) or symptom (e.g., hallucinations, agitation, paranoia) (MDS-UPDRS 1.2 and/or 1.3 > 2)
- •Patients who had a recent suicidal attempt (active, interrupted, aborted) within the past five years or report suicidal ideation within the past 6 months.
- •presence of dementia (MDS-UPDRS 1.1 > 2, Mini-Mental State Examination of <24 at the Screening visit)
- •clinically significant or unstable medical or surgical condition at Screening or Baseline visit that may preclude safety and the completion of the study participation (based on the investigator's judgment).
- •Patients with moderate or severe hepatic or renal impairment.
- •Patient has a history of chronic alcohol or drug abuse within the last 2 years.
- •women of child-bearing potential who do not practice an acceptable method of birth control
- •Pregnant women or women planning to become pregnant during the course of the study and nursing women.
- •Patients who are knowingly hypersensitive to any of the components of the investigational medicinal product or excipients.
- •Patient is legally incapacitated or persons held in an institution by legal or official order
- •Persons with any kind of dependency on the investigator or employed by the Sponsor or investigator
研究组 & 干预措施
Treatment Group
Nabilone 0.25 mg
干预措施: Nabilone 0.25 mg (Drug)
Placebo Group
Placebo (corn starch)
干预措施: Placebo (Drug)
结局指标
主要结局
Changes of Non-motor Symptoms
时间窗: from baseline to 4 weeks + 2 days
Changes in Movement Disorders Society - Unified Parkinson´s Disease Rating Scale (MDS-UPDRS) Part I minimum points: 0, maximum points: 52, higher score values indicate a worse outcome.
次要结局
- Incidence of AEs and Number of Withdrawals in PD Patients Taking Nabilone.(from baseline to 4 weeks + 2 days)
- Suicidality in PD Patients Taking Nabilone.(from baseline to 4 weeks + 2 days)
- Change in Hallucinations in PD Patients Taking Nabilone(from baseline to 4 weeks + 2 days)
- Orthostatic Hypotension in PD Patients Taking Nabilone(from baseline to week 4 + 2 days)
- Day-time Sleepiness in PD Patients Taking Nabilone: MDS-UPDRS(from baseline to week 4 + 2 days)
- Changes in Motor and Different Non-motor Symptoms of PD(from baseline to 4 weeks + 2 days)
- Changes in Different Domains of Non-motor Symptoms of PD(from baseline to 4 weeks + 2 days)
- Changes in Non-motor Symptoms of PD(from baseline to 4 weeks + 2 days)
- Clinical Global Impression - Global Improvement (CGI-I) Scale(Values of the Termination visit (4 weeks + 2 days from baseline))
- Changes in Temperature (Degree Celsius) in PD Patients Taking Nabilone.(from baseline to week 4 + 2 days)
- Changes in Supine and Standing Blood Pressure Measurements (mmHg) in PD Patients Taking Nabilone.(values from baseline and week 4 + 2 days)
- Subject Incompliance in PD Patients Taking Nabilone(from baseline to week 4 + 2 days)
- Weight (kg) in PD Patients Taking Nabilone.(from baseline to week 4 + 2 days)
- Changes in Quality of Life of PD(from baseline to week 4 + 2 days)
研究者
Klaus Seppi, MD
Principal Investigator
Medical University Innsbruck