2023-508932-68-00招募中2 期
A Double-blind, Randomized, Placebo-controlled, 4-arm Parallel-group, Multiple-Dose Study to Assess Efficacy and Safety of Medical Cannabis Aerosol via the Fixed-dose Syqe Inhaler as an Add-on Treatment of Diabetic Peripheral Neuropathic Pain
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 137
- 试验地点
- 33
- 主要终点
- 1. Change from baseline in weekly-mean 24-hour average pain score (using the 11-point Numeric Rating Scale [NRS]) at Week 16.
研究概览
简要总结
To evaluate the efficacy of medical cannabis (MC) aerosol containing 0.25, 0.5, 1.0 mg Δ9- tetrahydrocannabinol (THC) inhaled three times a day (TID) compared to placebo on pain intensity at Week 16.
研究设计
- 分配方式
- Randomized
- 主要目的
- Safety Follow-up Period
- 盲法
- Double (Analyst, Monitor, Carer, Investigator, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Able to comprehend and willing to sign the informed consent form (ICF), and willing to abide by the study restrictions.
- •Not current cannabis products users, i.e., patients who were previous cannabis products users for any reason but have not used any cannabis-based products (including CBD only) within 30 days of the screening visit, or patients who have never used cannabis, i.e., cannabis naïve patients.
- •A diagnosis of DPNP (at screening), including: • Daily, symmetrical foot pain in diabetic patients, present for at least 3 months, associated with definite or probable peripheral neuropathic pain and classified ≥3 using the Michigan Neuropathy Screening Instrument Part B at screening And • A mean average pain intensity score of ≥4 and ≤9 (Numeric Rating Scale [NRS]; the absolute range of scores [maximum score − minimum score] not exceeding 4) assessed during the last 7 days prior to randomization.
- •Confirmed diagnosis of diabetes mellitus type I or type II with stable disease, i.e., patient’s blood glucose to have been controlled by 1 or a combination of the following: diet, glucose control medication, or insulin, all on a stable dose for ≥3 months prior to screening.
- •Hemoglobin A1c ≤10% at screening.
- •Body mass index between 18 and 40 kg/m2, inclusive, at screening.
- •During the screening period, have at least 5 out of 7 records of daily average pain intensity recordings in the 7 days prior to randomization.
- •Female patients must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to the administration of study treatment on Day 1; alternatively, female patients of non-child-bearing potential must fulfil 1 of the following criteria at screening: • Post-menopausal defined as aged more than 50 years old and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. • Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and having luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range as per the central laboratory assessments. • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
- •Patients of reproductive potential and sexually active must use effective birth control methods, defined as: • For females: hormonal contraceptives, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, abstinence for duration of the trial (if it is patient lifestyle choice). • For males: vasectomy, or abstinence for duration of the trial (if it is patient lifestyle choice). Condom could be used by patients who are not vasectomized or do not agree with abstinence, its use must be in combination with a highly effective contraceptive method by the female partner or woman of childbearing potential.
- •Males and females aged ≥18 to ≤75 years at screening.
- •Agree to use only MC provided by study team until EOS and not to use any other cannabis or cannabis-containing products including, but not limited to products that are smoked, inhaled, ingested, or topically administered, or over-the-counter CBD products.
- •Agree not to participate in other interventional clinical studies during participation in this study.
- •Treated with standard of care for DPNP, defined as either duloxetine, gabapentin or pregabalin as monotherapy or a combination of 2, or patients who discontinued the use of standard of care, or amitriptyline used for the management of pain related to DPNP, at least 3 months prior to screening. The standard of care treatment and dosage must have been stable for at least 30 days prior to screening and without intention to change during the study. Patients who receive non-pharmacological, non-invasive pain therapy e.g., behavioral, or cognitive therapy etc., are allowed to enroll, provided there was no change reported to these therapies within 3 months before screening and no changes planned during the study.
排除标准
- •Evidence of significant uncontrolled concomitant disease that, in the judgment of the investigator, could affect compliance with the protocol at screening or randomization, ability to complete the study, and study assessments.
- •Presence of pain not associated with diabetic peripheral neuropathy or other neuropathies that may interfere with study assessments, as per Investigator’s judgement.
- •History of acute coronary syndrome in the last 12 month ; unstable angina; congestive heart failure; cardiogenic syncope; cardiomyopathy or; uncontrolled blood pressure at screening OR UP1 visits, defined as: • Systolic blood pressure ≤90 mm Hg or ≥140 mm Hg, or • Diastolic blood pressure ≤50 mm Hg or ≥95 mm Hg, or • Orthostatic hypotension with a decrease in systolic blood pressure of ≥ 20 mm Hg or a decrease in diastolic blood pressure of ≥10 mm Hg 3 minutes after rising from supine to standing, and • Orthostatic hypotension manifested by symptoms, e.g. lightheadedness, dizziness, syncope, and blurred vision after rising from supine to standing, or • Pulse rate at screening or UP1 visits of ≥120 bpm or ≤50 bpm.
- •Known history of significant hypersensitivity, intolerance, adverse reaction or allergy to cannabis products, cannabinoids, or acetaminophen/paracetamol.
- •Malignancies in the past 5 years prior to screening, except for cutaneous basal cell or squamous cell carcinoma resolved by excision.
- •Liver disease or liver injury as indicated by abnormal liver function tests at screening including elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), or total bilirubin exceeding 2 × upper limit of normal.
- •History or presence of impaired renal function at screening. • Clinically significant renal insufficiency chronic kidney disease (CKD) <3 or an estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 (Inker 2021) equation of < 30 mL/min ÷ 1.73 m2 at screening (as calculated by the central laboratory). • Evidence of urinary obstruction or difficulty in voiding at screening.
- •Pulmonary conditions: a) Abnormal lung function testing indicates forced expiratory volume in the first second (FEV1) <80% predicted value and FEV1/forced vital capacity ratio <70%. b) Presence or history of pulmonary diseases at screening: History of acute or chronic obstructive pulmonary disease (COPD); presence of asthma or • History of diagnosis of any pulmonary disease (interstitial lung disease, pulmonary hypertension, etc) in the judgment of the investigator is likely to be exacerbated by use of the Syqe Fixed-dose Inhaler.
- •Ongoing respiratory tract infection.
- •Female patients who are breast feeding or pregnant (including a positive serum pregnancy test at screening or a positive urine pregnancy test on Day 1).
- •Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, atrial fibrillation, paroxysmal supraventricular arrhythmia, second- or third-degree atrioventricular block without a pacemaker, or any other relevant cardiac disease as judged by the investigator.
- •History of epilepsy or other seizure disorders (except childhood febrile convulsions).
- •History of clinically significant ECG abnormalities, known familial long QT syndrome or familial ventricular arrythmia, or any clinically significant ECG abnormalities at screening or baseline, including: • QRS complex >120 msec • QTcF >450 msec for men, >470 msec for women • Acute ischemic changes.
- •History or presence of mental illness evidenced by • History of recurrent or ongoing major depressive disorders, mania, bipolar disorder, suicidality or a psychotic disorder, or • Family history of schizophrenia or other psychotic illness, or • Current psychiatric condition requiring treatment with a prohibited medication (see prohibited medication list in Section 9.5.2), or • Results from the Columbia-Suicide Severity Rating Scale (C-SSRS) and Mini International Neuropsychiatric Interview (MINI)-Standard (Modules A, C, K, O and diagnostic algorithm at screening, that in the judgment of the investigator indicates history or presence of mental illness, or • Any other current psychiatric condition that might interfere with ability to participate in the study.
- •Abnormal neurological condition or abnormal neurological examination other than related to DPN as judged by the investigator at screening that impacts the assessment of study endpoints.
- •History of immunodeficiency diseases, including a positive human immunodeficiency virus test result (as per local guidance) at screening.
- •A positive hepatitis B surface antigen or hepatitis C test result at screening, unless chronic or acute infection can be ruled out.
- •History or presence of drug or alcohol abuse or evidence of such abuse as indicated by the laboratory assays conducted during screening (including Δ9-THC and opiates).
- •Presence of skin conditions in the affected dermatome at screening or randomization that, in the judgment of the investigator, could interfere with the evaluation of the neuropathic pain condition.
- •Inadequate hematological function, defined as neutrophil count <1.5 × 109/L and/or platelet count <100 × 109/L at screening.
- •History of irreversible neurolytic or neurosurgical therapies, or recent other nonpharmacological treatments that, in the opinion of the investigator, may influence the result of the study assessments.
- •Prior use of the Syqe Inhaler for the administration of cannabis sativa L ‘Afina’ aerosol.
- •Plans to change current medications or any other intervention intended to treat or relieve DPNP signs or symptoms from screening to EOS.
- •Use of prohibited medications as per Section 9.5.2, or participation in an interventional clinical study within 30 days prior to screening.
- •Any factor or condition likely to affect compliance, study intervention, visit plan, assessments, scientific integrity, or any clinically significant medical condition which might be worsened by study treatment as judged by the investigator.
结局指标
主要结局
1. Change from baseline in weekly-mean 24-hour average pain score (using the 11-point Numeric Rating Scale [NRS]) at Week 16.
1. Change from baseline in weekly-mean 24-hour average pain score (using the 11-point Numeric Rating Scale [NRS]) at Week 16.
次要结局
- 1. Change from baseline in Neuropathic Pain Symptom Inventory and in Brief Pain Inventory – Short Form.
- 2. Change from baseline in weekly-mean 24-hour average, worst and least pain score (using the 11-point NRS).
- 3. Proportion of patients achieving at least 30% and 50% reduction from baseline in the weekly-mean 24-hour average pain score (using the 11-point NRS).
- 4. Proportion of patients with treatment-emergent adverse events (TEAEs) and their severity, AEs leading to study treatment discontinuation, TEAEs of special interest, and serious TEAEs.
- 5. Safety and tolerability will also be assessed by Michigan Neuropathy Screening Instrument Part B, Columbia-Suicide Severity Rating Scale, spirometry, electrocardiogram, laboratory blood, and urine tests.
- 6. Pharmacokinetic concentrations and parameters (pre-dose plasma concentration [Ctrough], maximum observed steady state concentration [Cmax ss], time at which maximum observed steady state concentration occurs [Tmax ss], area under the concentration-time curve [AUC]) of Δ9-THC, cannabidiol, cannabinol, 11-OH-THC, and 11-COOH-THC at selected visits.
- 7. Proportion of patients who need rescue medication for the treatment of DPNP.
- 8. Frequency and amount of rescue medication taken and time to first intake for the treatment of DPNP.
- 9. Change from baseline in weekly-mean 24-hour sleep score using the 11-point Daily Sleep Interference Scale and the Pain and Sleep Questionnaire-3.
- 10. Change from baseline in Patient-Reported Outcomes Measurement Information System-29 Profile v2.1 total score.
研究者
Ayelet Grinhut
Scientific
Syqe Medical Ltd.
研究点 (33)
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