Dronabinol; Cannabidiol for Multiple sclerosis | Chronic neuropathic pain

Inclusion criteria

• {"criterion_text":"- Native Portuguese speakers who provided free written informed consent prior to any procedure required by the study.\n- Stable dose of Disease Modifying Therapies (DMTs) for at least 6 months and willingness to maintain this regimen for the duration of the study\n- 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\n- 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).\n- 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\n- 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.)\n- A male patient must be willing not to donate sperm from admission until 3 months days following the last investigational product administration\n- 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\n- Male or female subjects with age between 18 to 65 years old, inclusive at the time of signing the informed consente\n- No clinically relevant abnormalities on vital signs\n- No clinically relevant abnormalities on 12-lead ECG\n- No clinically relevant abnormalities on clinical laboratory tests\n- 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)\n- Chronic neuropathic pain due to MS for at least 6 months\n- Patients refractory or intolerante to at least one drug for the treatment of chronic neuropathic pain."}

Exclusion criteria

• {"criterion_text":"- Pain symptom that could clearly be attributed to reasons other than neuropathic pain, as judgment of principal Investigator\n- If WOCBP, positive pregnancy test in urine\n- Any other condition that the Investigator considers to render the patient unsuitable for the study period\n- Known or suspected hypersensivity to cannabinoids or any of the excipients of the study medication.\n- Patients who did not attain clinical benefit by the end of the treatment period\n- Veins unsuitable for intravenous puncture on either arm\n- Unable to attain the 25 mg + 25 mg dose\n- History of epilepsy\n- 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).\n- Known or suspected history of alcohol or substance abuse\n- Any clinically significant cardiovascular or respiratory conditions that could be exacerbated by THC:CBD use\n- Baseline QTcF interval >450 msec if man or >470 msec if woman, or <350 msec\n- Patients on warfarin, insulin and/or sulfonylureas.\n- Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months\n- If woman of childbearing potential (WOCBP), positive pregnancy test Se mulher com potencial para engravidar (WOCBP), teste de gravidez positivo.\n- Patients with severe unstable cardiovascular disease\n- Use of cannabinoids or cannabinoid-based medications within 30 days prior to screening and unwillingness to abstain for the duration for the study\n- 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.\n- Patients with liver failure (Child-Pugh B or C)\n- Scheduled elective surgery or other procedures, which require general anaesthesia during the study\n- 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)\n- 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.\n- Systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <60 mmHg\n- 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.\n- If woman, she is breast-feeding\n- Positive result in urine ethanol test.\n- Patients who did not take the last four doses of IMP as per protocol.\n- 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.\n- Estimated renal creatinine clearance (CLCr) <60 mL/min, based on creatinine clearance calculation by the Cockcroft-Gault formula\n- Participation in another clinical trial within 30 days prior to screening\n- 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\n- Average NRS pain score <4 points during the screening period (mean of the last four available ratings in the 7 days prior to the visits).\n- New pain treatments or significant changes in existing pain treatments during the screening period"}

Primary endpoints

• {"endpoint_text":"- 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 mean of the last four available ratings in the 7 days prior to a study visit will be considered.","definition_or_measurement_approach":"Change in pain intensity 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 mean of the last four available ratings in the 7 days prior to a study visit will be considered."}

Secondary endpoints

• {"endpoint_text":"- Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment","definition_or_measurement_approach":"Proportion of patients with ≥30% reduction in pain NRS 0-10 after 4 weeks of optimized treatment."}
• {"endpoint_text":"- Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 4 weeks of optimized treatment","definition_or_measurement_approach":"Proportion of patients with ≥50% reduction in pain NRS 0-10 after 4 weeks of optimized treatment."}
• {"endpoint_text":"- Efficacy: Change in pain intensity as measured by the NRS 0-10 between baseline (Day 1) and 12 weeks of optimized treatment","definition_or_measurement_approach":"Change in pain intensity measured by NRS 0-10 between baseline and 12 weeks of optimized treatment."}
• {"endpoint_text":"- Efficacy: Proportion of patients who achieved at least a 30% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment","definition_or_measurement_approach":"Proportion of patients with ≥30% reduction in pain NRS 0-10 after 12 weeks of optimized treatment."}
• {"endpoint_text":"- Efficacy: Proportion of patients who achieved at least a 50% reduction in their pain NRS 0-10 score after 12 weeks of optimized treatment","definition_or_measurement_approach":"Proportion of patients with ≥50% reduction in pain NRS 0-10 after 12 weeks of optimized treatment."}
• {"endpoint_text":"- Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 4 weeks of optimized treatment.","definition_or_measurement_approach":"Proportion of patients with ≥30% reduction in spasticity NRS 0-10 after 4 weeks."}
• {"endpoint_text":"- Efficacy: Proportion of patients who achieved at least a 30% reduction in spasticity NRS 0-10 score after 12 weeks of optimized treatment.","definition_or_measurement_approach":"Proportion of patients with ≥30% reduction in spasticity NRS 0-10 after 12 weeks."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Change in spasticity measured by NRS 0-10 at baseline vs 4 and 12 weeks; scale 0-10 with definitions provided."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in PSQI component and global scores between baseline and 4 and 12 weeks."}
• {"endpoint_text":"- Efficacy: Change in EuroQol 5-Dimensions, 5-Levels (EQ-5D-5L) index score between baseline (Day 1) and 12 weeks of optimized treatment","definition_or_measurement_approach":"Change in EQ-5D-5L index score between baseline and 12 weeks."}
• {"endpoint_text":"- Efficacy: Change in EQ-5D-5L visual analogue scale (VAS) score between baseline (Day 1) and 12 weeks of optimized treatment","definition_or_measurement_approach":"Change in EQ-5D-5L VAS score from baseline to 12 weeks."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion of patients reporting improvement per PGIC at 4 and 12 weeks."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in EDSS score between baseline and 4 and 12 weeks."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change in NHPT completion time between baseline and 4 and 12 weeks."}
• {"endpoint_text":"- Efficacy: Reduction of at least a 30% Neuropathic Pain Symptom Inventory (NPSI) score after 4 and 12 weeks of optimized treatment.","definition_or_measurement_approach":"Proportion with ≥30% reduction in NPSI score at 4 and 12 weeks."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Incidence and reporting of TEAEs, SAEs, AEs leading to discontinuation; clinically relevant abnormalities in vital signs, ECG and labs reported as AEs."}

Portugal

Earliest CTIS Part Ii Submission Date

26-05-2025

Latest Decision Or Authorization Date

13-01-2026

Processing Time Days

232

Number Of Sites

1

Number Of Participants

68

Primary sponsor

Full Name

Ferraz Lynce Especialidades Farmaceuticas S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Portugal

Third parties

• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Portugal","full_name":"Blueclinical Investigacao E Desenvolvimento Em Saude Lda.","duties_or_roles":"sponsorDuties codes: 6, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Portugal","full_name":"CCAB Centro Clinico Academico Braga Associacao","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Kymos S.L.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}