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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-508932-68-00 | EU Trial (CTIS) Number |
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The primary purpose of this study is to evaluate the safety and efficacy of medical cannabis aerosol containing 0.25, 0.50, 1.0 milligrams (mg) delta (Δ) 9-tetrahydrocannabinol (THC) inhaled three times a day (TID) compared to placebo via the Fixed-dose Syqe Inhaler on pain intensity at Week 15.
This study will assess the efficacy, safety, tolerability, and pharmacokinetics (PK) of medical cannabis aerosol inhaled via the Syqe Inhaler at nominal doses of 0 (placebo), 0.25, 0.5, and 1.0 mg TID of Δ9-THC added on to standard of care for treatment of DPNP.
The target sample size is 192 eligible participants worldwide, randomized from up to approximately 51 recruiting sites in up to approximately 8 countries.
The study consists of 1) a screening period of up to 14 days; 2) a 15-week, parallel-group, randomized, double-blind treatment period, including a 3-week up-titration period and a 12-week maintenance period; and 3) a post-treatment, safety follow-up period of 4 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants will receive placebo, inhaled TID via the Fixed-dose Syqe Inhaler. |
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| 0.25 mg THC | Experimental | Participants will inhale medical cannabis aerosol containing 0.25 mg THC via the Fixed-dose Syqe Inhaler three times a day. |
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| 0.5 mg THC | Experimental | Participants will inhale medical cannabis aerosol containing 0.5 mg THC via the Fixed-dose Syqe Inhaler three times a day. |
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| 1.0 mg THC | Experimental | Participants will inhale medical cannabis aerosol containing 1.0 mg THC via the Fixed-dose Syqe Inhaler three times a day. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Medical Cannabis | Drug | Syqe cartridge containing medical cannabis (Bedrocan®) administered using Fixed-dose Syqe Inhaler. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Weekly-mean 24-hour Average Pain Score on the Numeric Rating Scale (NRS) at Week 15 | The NRS is an 11-point scale with scores ranging from 0 (no pain) to 10 (worst pain imaginable) for measuring participant self-reporting of pain intensity. A reduction in the score over time represents an improvement. | Baseline and at Week 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) | The NPSI is a 12-items patient reported outcome (PRO) measure that contains 10 descriptors representing 5 dimensions of pain (burning pain, deep/pressing pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia), and 2 temporal items designed to assess pain duration and the number of pain paroxysms. Total score range for NPSI is 0-100, higher scores indicate more severity. |
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Inclusion Criteria:
Exclusion Criteria:
Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol at screening or randomization, ability to complete the study, or study assessments.
Presence of skin conditions in the affected dermatome at screening or randomization that could interfere with the evaluation of the neuropathic pain condition.
Presence of pain not associated with diabetic peripheral neuropathy (DPN) or other neuropathies that may interfere with study assessments.
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.
History or presence of impaired renal function at screening
Presence of significant pulmonary disease at screening
Ongoing respiratory infection.
History of acute coronary syndrome in the last 12 months; unstable angina; congestive heart failure; cardiogenic syncope; cardiomyopathy; or symptomatic arrhythmia, or current uncontrolled blood pressure.
Concomitant clinically significant cardiac arrhythmias, examples, sustained ventricular tachycardia, and second or third degree atrioventricular block without a pacemaker, or any other relevant cardiac disease in the judgment of the investigator.
History of clinically significant electrocardiograms (ECG) abnormalities, or any of the following ECG abnormalities at screening or baseline:
History or presence of mental illness evidenced as defined in the protocol.
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.
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| Name | Affiliation | Role |
|---|---|---|
| Edith Dekel | Syqe Medical Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Innovate Clinical Research | Waitara | New South Wales | 2077 | Australia | ||
| Western Sydney University NICM Health Research Institute (NICM HRI) |
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| Placebo | Drug | Placebo administered using Fixed-dose Syqe Inhaler. |
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| Baseline up to Week 19 |
| Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Scale | The BPI-SF allows participants to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function using a 0 to 10 NRS. A higher score indicates more severity or more interference. | Baseline up to Week 19 |
| Change From Baseline in Weekly-mean 24-hour Average, Worst and Least Pain Score on the NRS | The NRS is an 11-point scale with scores ranging from 0 (no pain) to 10 (worst pain imaginable) for measuring participant self-reporting of pain intensity. A reduction in the score over time represents an improvement. | Baseline up to Week 19 |
| Proportion of Participants Achieving at least 30 Percent (%) and 50% Reduction From Baseline in the Weekly-mean 24-hour Average Pain Score on the NRS | The NRS is an 11-point scale with scores ranging from 0 (no pain) to 10 (worst pain imaginable) for measuring participant self-reporting of pain intensity. A reduction in the score over time represents an improvement. | Baseline up to Week 19 |
| Proportion of Participants with Treatment-emergent Adverse Events (TEAEs) and Their Severity | Baseline up to Week 19 |
| Proportion of Participants With Adverse Events (AEs) Leading to Study Treatment Discontinuation and Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs). | Baseline up to Week 19 |
| Assessment of Diabetic Neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) - Part B | The MNSI Part B consists of visual inspection of the feet and assessment of ankle reflexes, vibration sense, and monofilament testing. The measure is a score between 0 (normal) and 10 (most severe). | Baseline up to Week 19 |
| Assessment of Suicidal Ideation and Behavior using the Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is a semi-structured interview to assess the presence and severity of suicidal ideation and behavior. | Baseline up to Week 19 |
| Assessment of Withdrawal Symptoms After Termination of Study Treatment using the Study Medication Withdrawal Questionnaire Version 2 (SMWQ V2) | The SMWQ V2 is a 10-item patient-reported measure, where responses related to withdrawal symptoms are rated on 5-level Lickert scales between 0 (not at all) and 4 (very much). | Baseline up to Week 19 |
| Number of Participants With Clinically Significant Abnormal Lung Function Measured using Spirometry | Spirometry is a test that measures how much air can be breathed out in one forced breath. It is used to measure acute effects of study treatment on lung function. Spirometry testing will include measurement of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC. | Baseline up to Week 19 |
| Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG) | An ECG is a test that records the electrical activity of the heart. It is used to measure acute effects of study treatment on heart function. | Baseline up to Week 19 |
| Number of Participants With Clinically Significant Abnormality in Blood and Urine Parameters | A variety of laboratory tests will be used to identify any clinically significant abnormalities. | Baseline up to Week 19 |
| Pharmacokinetics - Ctrough | Pre-dose plasma concentration (Ctrough) of Δ9-THC, cannabidiol, cannabinol, 11-OH-THC, and 11-COOH-THC. | At selected visits from baseline up to Week 16 |
| Pharmacokinetics - Cmax,ss | Maximum observed plasma steady state concentration (Cmax,ss) for Δ9-THC, cannabidiol, cannabinol, 11-OH-THC, and 11-COOH-THC. | At selected visits from baseline up to Week 16 |
| Pharmacokinetics - Tmax,ss | Time to reach maximum observed plasma steady state concentration (Tmax,ss) for Δ9-THC, cannabidiol, cannabinol, 11-OH-THC, and 11-COOH-THC. | At selected visits from baseline up to Week 16 |
| Pharmacokinetics - AUC | Area under the concentration-time curve (AUC) for Δ9-THC, cannabidiol, cannabinol, 11-OH-THC, and 11-COOH-THC. | At selected visits from baseline up to Week 16 |
| Proportion of Participants who Need Rescue Medication for the Treatment of DPNP | Baseline up to Week 19 |
| Frequency of Rescue Medication Taken for the Treatment of DPNP | Baseline up to Week 19 |
| Amount of Rescue Medication Taken for the Treatment of DPNP | Baseline up to Week 19 |
| Time to First Intake of Rescue Medication Taken for the Treatment of DPNP | Baseline up to Week 19 |
| Change From Baseline in Weekly-mean 24-hour Sleep Score Using the Daily Sleep Interference Scale (DSIS) | The DSIS diary consists of an 11-point Likert scale with which participants assess how pain has interfered with their sleep during the past 24 hours. On this scale a 0 indicates "pain does not interfere with sleep" and 10 indicates "pain completely interferes with sleep." A higher score indicates more inference of pain with sleep. | Baseline up to Week 19 |
| Change From Baseline in Sleep Score Using the Pain and Sleep Questionnaire-3 (PSQ-3) | The PSQ-3, also called Chronic Pain Sleep Inventory©, is a patient-reported 3-item index to assess the impact of chronic pain on sleep over the past 7 days. Each item is reported on a visual analog scale (VAS) between "never" and "always". The score ranges from 0 to 100. | Baseline up to Week 19 |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile Total Score | PROMIS-29 Profile v2.1 is a set of person-centered measures that evaluates and monitors physical, mental, and social health. PROMIS-29 Profile v2.1 consists of 7 domains with a total of 29 questions answered on Lickert scales. | Baseline up to Week 19 |
| Westmead |
| New South Wales |
| 2145 |
| Australia |
| Westmead Hospital | Westmead | New South Wales | 2145 | Australia |
| Emeritus Research | Camberwell | Victoria | 3124 | Australia |
| The Royal Melbourne Hospital | Parkville | Victoria | 3050 | Australia |
| Rychnov nad Kneznou, Hradec Kralove | Rychnov nad Kněžnou | Hradec Kralove | 516 01 | Czechia |
| Ostrava, Ostrava City | Ostrava | Ostrava City | 71000 | Czechia |
| Plzen, Plzen City | Pilsen | Plzen City | 30100 | Czechia |
| Prague, Praha 12 | Prague | Prague | 12000 | Czechia |
| Heidelberg, Baden-Wuerttemberg | Heidelberg | Baden-Wurttemberg | 69115 | Germany |
| Karlsruhe, Baden-Württemberg | Karlsruhe | Baden-Wurttemberg | 76137 | Germany |
| Ulm, Baden-Württemberg | Ulm | Baden-Wurttemberg | 89073 | Germany |
| Hamburg, Hamburg | Hamburg | Free and Hanseatic City of Hamburg | 20253 | Germany |
| Hannover, Lower Saxony | Hanover | Lower Saxony | 30449 | Germany |
| Schwerin, Mecklenburg | Schwerin | Mecklenburg | 19053 | Germany |
| Reinfeld, Schleswig-Holstein | Reinfeld | Schleswig-Holstein | 23858 | Germany |
| Berlin, Berlin 4010 | Berlin | State of Berlin | 10629 | Germany |
| Berlin, Berlin | Berlin | State of Berlin | 13187 | Germany |
| Klinische Forschung Dresden GmbH | Dresden | 3109601 | Germany |
| Klinische Forschung Schwerin GmbH | Schwerin | 19055 | Germany |
| The Edith Wolfson Medical Center | Holon | Tel Aviv | 58100 | Israel |
| Sheba Medical center Hospital | Ramat Gan | Tel Aviv | 5262100 | Israel |
| Barzilai Medical center | Ashkelon | 7830604 | Israel |
| Bnai Zion Medical Center | Haifa | 3104802 | Israel |
| Rambam Medical Center | Haifa | 3109601 | Israel |
| Hadassah Medical Center | Jerusalem | 91120 | Israel |
| Beilinson hospital/ Petach Tikva | Petah Tikva | 4941492 | Israel |
| Ziv Medical Center | Safed | 13100 | Israel |
| Swidnica, Dolnoslaskie | Swidnica | Lower Silesian Voivodeship | 58-100 | Poland |
| Sochaczew, Mazowieckie | Sochaczew | Masovian Voivodeship | 96-500 | Poland |
| Warszawa, Mazowieckie 7011 | Warsaw | Masovian Voivodeship | 01-018 | Poland |
| Warszawa, Mazowieckie | Warsaw | Masovian Voivodeship | 02-172 | Poland |
| Warszawa, Mazowieckie 7010 | Warsaw | Masovian Voivodeship | 02-677 | Poland |
| Katowice, Silesia | Katowice | Silesian Voivodeship | 40-282 | Poland |
| Katowice, Śląsk | Katowice | Silesian Voivodeship | 40-748 | Poland |
| Centrum Medyczne NEUROMED | Bydgoszcz | 85-163 | Poland |
| Centrum Medyczne Pratia Chojnice | Chojnice | 89-600 | Poland |
| Osrodek Badan Klinicznych Neuro-Medic Clinic | Katowice | 40-686 | Poland |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D003929 | Diabetic Neuropathies |
| D002189 | Marijuana Abuse |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D064086 | Medical Marijuana |
| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
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