A phase II randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of an oral solution of 9-Δ tetrahydrocannabinol/cannabidiol (THC/CBD) in multiple sclerosis patients with chronic neuropathic pain
- Conditions
- Chronic neuropathic pain due to multiple sclerosis (MS)
- Registration Number
- 2024-520287-34-01
- Lead Sponsor
- Ferraz Lynce Especialidades Farmaceuticas S.A.
- Brief Summary
To evaluate the efficacy of an oral solution of THC:CBD (25 mg + 25 mg/mL) in relieving chronic neuropathic pain due to MS, after 4 weeks of optimized treatment compared with placebo
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 68
Native Portuguese speakers who provided free written informed consent prior to any procedure required by the study.
Stable dose of Disease Modifying Therapies (DMTs) for at least 6 months and willingness to maintain this regimen for the duration of the study
Stable regimen of concomitant medications and non-pharmacological therapies for at least 4 weeks prior to screening visit and willing to maintain these regimens for the duration of the study
A female patient is eligible if she meets one of the following criteria: - is of non-childbearing potential (refer to Section 6.4.- Contraception Requirements for the criteria for non-childbearing potential status); or - is of childbearing potential and agrees to use an highly effective contraceptive method (refer to Section 6.4.- Contraception Requirements for a list of accepted methods) from admission to study period until at least 3 months after the last investigational product administration. – Women choosing to use a hormonal contraceptive should also use a barrier method (condom).
A male patient who is sexually active with a female partner of childbearing potential (pregnant or non-pregnant) must use contraception (condom) from admission until at least 3 months following the last investigational product administration
A male patient must ensure that his non-pregnant female partner of childbearing potential agrees to consistently and correctly use for the same period a highly effective method of contraception (see Section 6.4.)
A male patient must be willing not to donate sperm from admission until 3 months days following the last investigational product administration
Willing to accept and comply with all study procedures and restrictions, including not driving motorized vehicles from first administration until EoS or safety follow-up
Male or female subjects with age between 18 to 65 years old, inclusive at the time of signing the informed consente
No clinically relevant abnormalities on vital signs
No clinically relevant abnormalities on 12-lead ECG
No clinically relevant abnormalities on clinical laboratory tests
Diagnosis of MS for more than 6 months, according to the 2017 revised McDonald criteria, including any subtype of MS (Relapsing-Remitting MS, Secondary Progressive MS, Primary Progressive MS, and Progressive-Relapsing MS)
Chronic neuropathic pain due to MS for at least 6 months
Patients refractory or intolerante to at least one drug for the treatment of chronic neuropathic pain.
Pain symptom that could be attributed to reasons other than neuropathic pain, as judgment of principal Investigator
Baseline QTcF interval >450 msec if man or >470 msec if woman, or <350 msec
Systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <60 mmHg
Known or suspected personal or family history of schizophrenia or other psychotic disorders, history of severe personality disorders, significant anxiety or depression (e.g., Hospital Anxiety and Depression Scale [HADS] ≥11), or any other significant psychiatric condition.
Estimated renal creatinine clearance (CLCr) <60 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula
Participation in another clinical trial within 30 days prior to screening
Any condition that, in the opinion of the Investigator may either put the subject at risk, would interfere with the patient's ability to comply with the study protocol or give informed consent
Average NRS pain score <4 points during the screening period (7 daily measurements)
New pain treatments or significant changes in existing pain treatments during the screening period
If WOCBP, positive pregnancy test in urine
Any other condition that the Investigator considers to render the patient unsuitable for the study period
Known or suspected hypersensivity to cannabinoids or any of the excipients of the study medication.
Patients who did not attain clinical benefit by the end of the treatment period
Veins unsuitable for intravenous puncture on either arm
Unable to attain the 25 mg + 25 mg dose
History of epilepsy
Use of the following medications , within 30 days prior to enrolment on the extension period: - inibitors of CYP3A4 isoenzymes such as macrolides (e.g., clarithromycinand erythromycin), antifungals (e.g., itraconazole, fluconazole, ketoconazole, and miconazole), HIV protease inibitors (e.g.ritonavir), and verapamil. – inducers of CYP3A4 such as carbamazepine, fenobarbital, phenytoin, rifampicin, efavirenz, rifabutin, and troglitazone. – strong inibitors of CYP2C9 (e.g. amiodarone, clopidogrel, fluconazole, fluoruracil, metronidazole, sulfamethoxazole, and valproic acid, St. John’s wort). – strong inducers of CYP2A9 (e.g., barbiturates, carbamazepine,phenytoin, rifampicin, rifabutin, and St. John’s wort). – strong inhibitors of CYP2C19 (e.g., chloramphenicol, clopidogrel, efavirenz, esomeprazole, fluconazole, fluoxetine, fluvoxamine, isoniazid, modafinil, omeprazole, oxcarbazepine, voriconazole). – strong inducers of CYP2C19 (e.g., barbiturates, carbamazepine, phenytoin, primidone, rifampicin, St. John’s wort).
Known or suspected history of alcohol or substance abuse
Any clinically significant cardiovascular or respiratory conditions that could be exacerbated by THC:CBD use
Patients on warfarin, insulin and/or sulfonylureas.
Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months
If woman of childbearing potential (WOCBP), positive pregnancy test Se mulher com potencial para engravidar (WOCBP), teste de gravidez positivo.
Patients with severe unstable cardiovascular disease
Use of cannabinoids or cannabinoid-based medications within 30 days prior to screening and unwillingness to abstain for the duration for the study
Posed a significant risk of a suicide attempt based on history or the Investigator’s judgment; answer “yes” to Suicidal Ideation items 4 or 5 on the C-SSRS for current or past 3 months on the “Baseline/Screening version”; have had suicidal behavior in his/her lifetime as measured by the C-SSRS; or are at imminent risk of suicide or violent behavior based on the Investigator’s clinical assessment or the C-SSRS assessment of lifetime suicidal ideation or behavior.
Patients with liver failure (Child-Pugh B or C)
Scheduled elective surgery or other procedures, which require general anaesthesia during the study
Use of the following medications, within 30 days prior to screening: - systemic corticoids, non-steroidal anti-inflammatory drugs other than those used at stable doses for conditions unrelated to neuropathic pain. - immunomodulatory or immunosuppressive therapies (other than DMTs)
Use of other concomitant medications and non-pharmacological therapies that may lead to patient non-enrolment in this study, according to Investigator judgment. * Unless therapeutic drug monitoring is available, digoxin, lithium, phenytoin, carbamazepine, valproate, clobazam, and theophylline will not be allowed.
Use of concomitant medications not on stable regímen for at least 4 weeks prior to screening visit or with a regímen that is expected to change during the study.
If woman, she is breast-feeding
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Efficacy: Change in pain intensity as measured by the Numeric Rating Scale (NRS 0-10) between baseline (Day 1) and 4 weeks of optimized treatment (corresponding to Week 6 visit); the average of the pain intensity measured over the period of 7 days prior to a study visit will be considered Efficacy: Change in pain intensity as measured by the Numeric Rating Scale (NRS 0-10) between baseline (Day 1) and 4 weeks of optimized treatment (corresponding to Week 6 visit); the average of the pain intensity measured over the period of 7 days prior to a study visit will be considered
- Secondary Outcome Measures
Name Time Method Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment
Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment
Efficacy: Change in pain intensity as measured by the NRS 0-10 between baseline (Day 1) and 12 weeks of optimized treatment Efficacy: Change in pain intensity as measured by the NRS 0-10 between baseline (Day 1) and 12 weeks of optimized treatment
Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment
Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment
Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 4 weeks of optimized treatment. Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 4 weeks of optimized treatment.
Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 12 weeks of optimized treatment. Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 12 weeks of optimized treatment.
Efficacy: Change in spasticity symptom measured by the NRS 0-10 between baseline (Day 1) and 4 weeks of optimized treatment and baseline and 12 weeks of optimized treatment (0: No spasticity - The patient experiences no increase in muscle tone or involuntary muscle spasms; 10: Worst possible spasticity - The patient experiences extreme muscle stiffness, severe spasms, and significant difficulty with movement) Efficacy: Change in spasticity symptom measured by the NRS 0-10 between baseline (Day 1) and 4 weeks of optimized treatment and baseline and 12 weeks of optimized treatment (0: No spasticity - The patient experiences no increase in muscle tone or involuntary muscle spasms; 10: Worst possible spasticity - The patient experiences extreme muscle stiffness, severe spasms, and significant difficulty with movement)
Efficacy: Change in Pittsburgh Sleep Quality Index (PSQI) component scores and global score between baseline (Day 1) and 4 weeks of optimized treatment and baseline and 12 weeks of optimized treatment Efficacy: Change in Pittsburgh Sleep Quality Index (PSQI) component scores and global score between baseline (Day 1) and 4 weeks of optimized treatment and baseline and 12 weeks of optimized treatment
Efficacy: Change in EuroQol 5-Dimensions, 5-Levels (EQ-5D-5L) index score between baseline (Day 1) and 12 weeks of optimized treatment Efficacy: Change in EuroQol 5-Dimensions, 5-Levels (EQ-5D-5L) index score between baseline (Day 1) and 12 weeks of optimized treatment
Efficacy: Change in EQ-5D-5L visual analogue scale (VAS) score between baseline (Day 1) and 12 weeks of optimized treatment Efficacy: Change in EQ-5D-5L visual analogue scale (VAS) score between baseline (Day 1) and 12 weeks of optimized treatment
Efficacy: Proportion of patients reporting improvement in their condition with Patient Global Impression of Change (PGIC) scale after 4 and 12 weeks of optimized treatment Efficacy: Proportion of patients reporting improvement in their condition with Patient Global Impression of Change (PGIC) scale after 4 and 12 weeks of optimized treatment
Efficacy: Change in the Expanded Disability Status Scale (EDSS) score between baseline (Day 1) and 4 weeks of optimized treatment and from baseline and 12 weeks of optimized treatment Efficacy: Change in the Expanded Disability Status Scale (EDSS) score between baseline (Day 1) and 4 weeks of optimized treatment and from baseline and 12 weeks of optimized treatment
Efficacy: Change in the Nine-Hole Peg test (NHPT) completion time from baseline (Day 1) and 4 weeks of optimized treatment and between baseline and 12 weeks of optimized treatment. Efficacy: Change in the Nine-Hole Peg test (NHPT) completion time from baseline (Day 1) and 4 weeks of optimized treatment and between baseline and 12 weeks of optimized treatment.
Efficacy: Reduction of at least a 30% Neuropathic Pain Symptom Inventory (NPSI) score after 4 and 12 weeks of optimized treatment. Efficacy: Reduction of at least a 30% Neuropathic Pain Symptom Inventory (NPSI) score after 4 and 12 weeks of optimized treatment.
Safety: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AE) leading to study discontinuation. Clinically relevant abnormalities in vital signs, 12-lead electrocardiogram (ECG) and laboratory parameters will be reported as AEs. Safety: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AE) leading to study discontinuation. Clinically relevant abnormalities in vital signs, 12-lead electrocardiogram (ECG) and laboratory parameters will be reported as AEs.
Trial Locations
- Locations (1)
CCAB Centro Clinico Academico Braga Associacao
🇵🇹Braga, Portugal
CCAB Centro Clinico Academico Braga Associacao🇵🇹Braga, PortugalJoão CerqueiraSite contact00351253027249joao.cerqueira@ccabraga.org