Clinical trial NCT06490445: A Study of Medical Cannabis Aerosol Via the Fixed-dose Syqe Inhaler as an Add-on Treatment of Diabetic Peripheral Neuropathic Pain (DPNP)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetic Peripheral Neuropathic Pain
Keywords: Diabetes
Neuropathy
Painful diabetic neuropathy
Chronic Neuropathic Pain
DPNP
Cannabis
Medical cannabis
Inhaled
Aerosol
Placebo
Randomized
Double-blind
Lead sponsor: Syqe Medical
Sponsor class: INDUSTRY
First posted: 2024-07-08
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Weekly-mean 24-hour Average Pain Score on the Numeric Rating Scale (NRS) at Week 15
timeFrame: Baseline and at Week 15
Secondary outcomes:
measure: Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI)
timeFrame: Baseline up to Week 19
measure: Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Scale
timeFrame: Baseline up to Week 19
measure: Change From Baseline in Weekly-mean 24-hour Average, Worst and Least Pain Score on the NRS
timeFrame: Baseline up to Week 19
measure: 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
timeFrame: Baseline up to Week 19
measure: Proportion of Participants with Treatment-emergent Adverse Events (TEAEs) and Their Severity
timeFrame: Baseline up to Week 19
measure: Proportion of Participants With Adverse Events (AEs) Leading to Study Treatment Discontinuation and Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs).
timeFrame: Baseline up to Week 19
measure: Assessment of Diabetic Neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) - Part B
timeFrame: Baseline up to Week 19
measure: Assessment of Suicidal Ideation and Behavior using the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 19
measure: Assessment of Withdrawal Symptoms After Termination of Study Treatment using the Study Medication Withdrawal Questionnaire Version 2 (SMWQ V2)
timeFrame: Baseline up to Week 19
measure: Number of Participants With Clinically Significant Abnormal Lung Function Measured using Spirometry
timeFrame: Baseline up to Week 19
measure: Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)
timeFrame: Baseline up to Week 19
measure: Number of Participants With Clinically Significant Abnormality in Blood and Urine Parameters
timeFrame: Baseline up to Week 19
measure: Pharmacokinetics - Ctrough
timeFrame: At selected visits from baseline up to Week 16
measure: Pharmacokinetics - Cmax,ss
timeFrame: At selected visits from baseline up to Week 16
measure: Pharmacokinetics - Tmax,ss
timeFrame: At selected visits from baseline up to Week 16
measure: Pharmacokinetics - AUC
timeFrame: At selected visits from baseline up to Week 16
measure: Proportion of Participants who Need Rescue Medication for the Treatment of DPNP
timeFrame: Baseline up to Week 19
measure: Frequency of Rescue Medication Taken for the Treatment of DPNP
timeFrame: Baseline up to Week 19
measure: Amount of Rescue Medication Taken for the Treatment of DPNP
timeFrame: Baseline up to Week 19
measure: Time to First Intake of Rescue Medication Taken for the Treatment of DPNP
timeFrame: Baseline up to Week 19
measure: Change From Baseline in Weekly-mean 24-hour Sleep Score Using the Daily Sleep Interference Scale (DSIS)
timeFrame: Baseline up to Week 19
measure: Change From Baseline in Sleep Score Using the Pain and Sleep Questionnaire-3 (PSQ-3)
timeFrame: Baseline up to Week 19
measure: Change From Baseline in Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Profile Total Score
timeFrame: Baseline up to Week 19
Other outcomes:
Locations:
city: Waitara
country: Australia
facility: Innovate Clinical Research
state: New South Wales
city: Westmead
country: Australia
facility: Western Sydney University NICM Health Research Institute (NICM HRI)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Rychnov Nad Kněžnou
country: Czechia
facility: Rychnov nad Kneznou, Hradec Kralove
state: Hradec Kralove
city: Ostrava
country: Czechia
facility: Ostrava, Ostrava City
state: Ostrava City
city: Plzen
country: Czechia
facility: Plzen, Plzen City
state: Plzen City
city: Prague
country: Czechia
facility: Prague, Praha 12
state: Praha
city: Heidelberg
country: Germany
facility: Heidelberg, Baden-Wuerttemberg
state: Baden-Wuerttemberg
city: Karlsruhe
country: Germany
facility: Karlsruhe, Baden-Württemberg
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Ulm, Baden-Württemberg
state: Baden-Württemberg
city: Hannover
country: Germany
facility: Hannover, Lower Saxony
state: Lower Saxony
city: Schwerin
country: Germany
facility: Schwerin, Mecklenburg
state: Mecklenburg
city: Reinfeld
country: Germany
facility: Reinfeld, Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Berlin, Berlin 4010
city: Berlin
country: Germany
facility: Berlin, Berlin
city: Dresden
country: Germany
facility: Klinische Forschung Dresden GmbH
city: Hamburg
country: Germany
facility: Hamburg, Hamburg
city: Schwerin
country: Germany
facility: Klinische Forschung Schwerin GmbH
city: H̱olon
country: Israel
facility: The Edith Wolfson Medical Center
state: Tel Aviv
city: Ramat Gan
country: Israel
facility: Sheba Medical center Hospital
state: Tel Aviv
city: Ashkelon
country: Israel
facility: Barzilai Medical center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Beilinson hospital/ Petach Tikva
city: Safed
country: Israel
facility: Ziv Medical Center
city: Swidnica
country: Poland
facility: Swidnica, Dolnoslaskie
state: Dolnoslaskie
city: Sochaczew
country: Poland
facility: Sochaczew, Mazowieckie
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa, Mazowieckie 7011
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa, Mazowieckie
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa, Mazowieckie 7010
state: Mazowieckie
city: Katowice
country: Poland
facility: Katowice, Silesia
state: Silesia
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne NEUROMED
city: Chojnice
country: Poland
facility: Centrum Medyczne Pratia Chojnice
city: Katowice
country: Poland
facility: Osrodek Badan Klinicznych Neuro-Medic Clinic
city: Katowice
country: Poland
facility: Katowice, Śląsk
state: Śląsk
Study officials:
affiliation: Syqe Medical Ltd.
name: Edith Dekel
role: STUDY_DIRECTOR
References: