A Study of Medical Cannabis Aerosol Via the Fixed-dose Syqe Inhaler as an Add-on Treatment of Diabetic Peripheral Neuropathic Pain (DPNP)

Phase 2RecruitingNCT06490445

Syqe Medical192 enrolled

Overview

The primary purpose of this study is to evaluate the efficacy of medical cannabis aerosol containing 0.25, 0.5, 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

192

Conditions

Diabetic Peripheral Neuropathic Pain

Interventions

Medical CannabisDRUG

Syqe cartridge containing medical cannabis (Bedrocan®) administered using Fixed-dose Syqe Inhaler.

PlaceboDRUG

Placebo administered using Fixed-dose Syqe Inhaler.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Able to comprehend and willing to sign the informed consent form (ICF), and willing to abide by the study restrictions. 2. Males and females aged between 18 (included) and 75 (included) years. 3. Agree to use only medical cannabis provided by study team until the end of study (EOS) and not to use any other cannabis or cannabis-containing products. 4. Agree not to participate in other interventional clinical studies during participation in this study. 5. Treated with standard of care for DPNP, either duloxetine or gabapentin or pregabalin as monotherapy or combination of 2. 6. Not current cannabis products users, that is, participants who were previous cannabis products users for any reason but have not used cannabis products within 3 months of the screening visit, or participants who have never used cannabis products, that is, cannabis naïve participants. 7. A diagnosis of DPNP (at screening). 8. Confirmed diagnosis of diabetes mellitus type I or type II with stable disease. 9. Glycated hemoglobin (HbA1c) less than (\<) 9% at screening. 10. Body mass index between 18 and 40 kilograms per square meter (kg/m\^2), inclusive. 11. Have at least 5 out of 7 records of daily average pain intensity recordings in the 7 days prior to randomization. 12. Agree not to drive or operate heavy machinery during the study treatment period. 13. Female participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to the administration of study treatment on Day 1or be of non-child-bearing potential as defined in the protocol. 14. Participants of reproductive potential who are sexually active must use effective birth control methods. Exclusion Criteria: 1. 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. 2. Presence of skin conditions in the affected dermatome at screening or randomization that could interfere with the evaluation of the neuropathic pain condition. 3. Presence of pain not associated with diabetic peripheral neuropathy (DPN) or other neuropathies that may interfere with study assessments. 4. Known history of significant hypersensitivity, intolerance, adverse reaction or allergy to cannabis products, cannabinoids, or acetaminophen/paracetamol. 5. Malignancies in the past 5 years prior to screening, except for cutaneous basal cell or squamous cell carcinoma resolved by excision. 6. Liver disease or liver injury as indicated by abnormal liver function tests at screening. 7. History or presence of impaired renal function at screening 8. Presence of significant pulmonary disease at screening 9. Ongoing respiratory infection at screening. 10. History of acute coronary syndrome; unstable angina; congestive heart failure; cardiogenic syncope; cardiomyopathy; or symptomatic arrhythmia, or current uncontrolled blood pressure. 11. 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. 12. History of clinically significant electrocardiograms (ECG) abnormalities, or any of the following ECG abnormalities at screening or baseline: * PR greater than (\>) 200 milliseconds (msec) * QRS complex \>120 msec * Fridericia QT correction formula (QTcF) greater than (\>) 450 msec * History of familial long QT syndrome or known family history of ventricular arrythmia. * Acute ischemic changes. 13. History or presence of mental illness evidenced as defined in the protocol. 14. Abnormal neurological condition or abnormal neurological examination at screening in judgment of investigator.

Locations (38)

Outcomes

Primary Outcomes

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.

Time frame: Baseline and at Week 15

Secondary Outcomes

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.

Time frame: 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.

Time frame: Baseline up to Week 19

Change From Baseline in Weekly-mean 24-hour Average, Worst and Least Pain Score on the NRS

Time frame: 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

Central Contacts

Head of Clinical Operations

CONTACT

+972 3-376-7338 edith.dekel@syqemed.com

Benny Schwartz, BSc

CONTACT

benny@syqemed.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Innovate Clinical Research

Waitara, New South Wales, Australia

NOT_YET_RECRUITING

Western Sydney University NICM Health Research Institute (NICM HRI)

Westmead, New South Wales, Australia

RECRUITING

Westmead Hospital

Westmead, New South Wales, Australia

ACTIVE_NOT_RECRUITING

Emeritus Research

Camberwell, Victoria, Australia

NOT_YET_RECRUITING

The Royal Melbourne Hospital

Parkville, Victoria, Australia

NOT_YET_RECRUITING

Rychnov nad Kneznou, Hradec Kralove

Rychnov nad Kněžnou, Hradec Kralove, Czechia

RECRUITING

Ostrava, Ostrava City

Ostrava, Ostrava City, Czechia

RECRUITING

Plzen, Plzen City

Pilsen, Plzen City, Czechia

RECRUITING

Prague, Praha 12

Prague, Prague, Czechia

RECRUITING

Heidelberg, Baden-Wuerttemberg

Heidelberg, Baden-Wurttemberg, Germany

RECRUITING

...and 28 more locations

Time frame: Baseline up to Week 19

Proportion of Participants with Treatment-emergent Adverse Events (TEAEs) and Their Severity

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to Week 19

Pharmacokinetics - Ctrough

Pre-dose plasma concentration (Ctrough) of Δ9-THC, cannabidiol, cannabinol, 11-OH-THC, and 11-COOH-THC.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: At selected visits from baseline up to Week 16

Proportion of Participants who Need Rescue Medication for the Treatment of DPNP

Time frame: Baseline up to Week 19

Frequency of Rescue Medication Taken for the Treatment of DPNP

Time frame: Baseline up to Week 19

Amount of Rescue Medication Taken for the Treatment of DPNP

Time frame: Baseline up to Week 19

Time to First Intake of Rescue Medication Taken for the Treatment of DPNP

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to Week 19