Different Dosage Regimens of Methocarbamol/Paracetamol in Acute Non-specific Low Back Pain. MioPain Study

Inclusion Criteria:

-Male and female patients of any ethnic origin between 18 and 64 years of age (limits included).

-Patients with current episode of acute (pain lasting less than 6 weeks) non-specific LBP, defined as pain and discomfort, localised below the costal margin and above the inferior gluteal folds, with or without leg pain, or acute exacerbation of chronic low back pain defined with a VAS score ≥ 40 mm.

• Patients with signs and symptoms of muscle spasm of the lumbar region, as clinicallydiagnosed by the Investigator.

• Women of childbearing potential and women with no menses for a period < 12 monthsmust have a negative pregnancy test at Visit 0 and have to agree not to start apregnancy from the signature of the informed consent up to the Final Visit/Visit 2,using an appropriate birth control method such as combined oestrogen-progestincontaining hormonal contraceptives (e.g., oral, injectable, transdermal),progestin-only hormonal contraceptives (e.g., oral, injectable, implantable),intrauterine device (IUD) or Intrauterine hormone-releasing System (IUS) incombination with male condom, bilateral tubal occlusion, vasectomised partner,sexual abstinence. The following definitions will be considered:

• Woman of childbearing potential (WOCBP): i.e., fertile, following menarche and untilbecoming post-menopausal, unless permanently sterile. Permanent sterilizationmethods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

• A postmenopausal state is defined as no menses for 12 months without an alternativemedical cause.

• Patients legally capable of giving their consent to participate in the study andavailable to sign and date the written Informed Consent.

Exclusion Criteria:

-1. Known hypersensitivity or allergy to the active ingredients and/or to any component of the study medications.

2. Lactating and pregnant women. 3. Clinically significant abnormalities on physicalexamination and vital signs at Visit 0 which in the opinion of the Investigatorcould interfere with the study procedures or endpoints evaluation.

3. Suspicious (according to the patient's symptoms at baseline) or confirmed COVID-19infection at time of screening visit.

4. History of cervical, thoracic, or lumbosacral pain for ≥75% of the time in the lastyear, or any other LBP episode in the last 3 months that required pharmacologicaltreatment with an opioid analgesic.

5. Patients with:

• serious spinal pathology; spinal surgery in the year prior to screening or historyof more than one spinal surgery; history of severe lumbar spinal stenosis;ankylosing spondylitis; lumbosciatalgia; herniated disc or radiculopathy; severearthritis and osteoporosis; muscular diseases, such as myositis, poliomyelitis,muscular dystrophy and myotonia; fibromyalgia; myasthenia grave; fracture or recenthistory of violent trauma of the back; structural deformity of the back;

• cancer, not in remission or in complete remission less than 1 year;

• active influenza or other viral syndrome; immunosuppression; systematically unwell;unexplained significant weight loss;

• women with polymenorrhea, endometriosis, ovarian cysts, uterine fibroids;

• widespread neurological symptoms (including cauda equina syndrome) or any braindisease; ever suffered from any brain damage or have been in a coma; epilepsy orseizures;

• active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration, orbleeding in the last 30 days;

• previous treatment with anticoagulants in the seven days before the screening visit;

• renal and/or hepatic failure;

• acute hepatitis;

• cardiac or pulmonary diseases;

• acetylsalicylic acid-triggered asthma;

• glucose-6-phosphate dehydrogenase-deficient patients; glutathione deficiency,dehydration, chronic malnutrition; anemia.

Any other condition that, in the opinion of the Investigator, interferes with the study endpoints/procedures and does not justify the inclusion of the patient in the study.

7. Current use of full, regular, recommended doses of any skeletal muscle relaxants/non

• opioid analgesics/anti-inflammatory/NSAIDs in the 6 hours prior to the screeningvisit. Use is forbidden for the entire trial duration.

8. Current use of full, regular, recommended doses of or any medication that can alterthe perception of pain (e.g., opioids, heparinoids, psychotropic agents, anti-H1agents or glucocorticosteroids, etc.), in the 24 hours prior to the screening visit.Use is forbidden for the entire trial duration.

Chronic intake of low doses of acetylsalicylic acid, i.e., ≤162 mg/daily, taken for at least 30 days prior to the first dose of study medication for non-analgesic reasons could be continued for the duration of the study.

9. Current use of the following medications (use is forbidden for the entire trialduration):

• systemic corticosteroids;

• other drugs containing paracetamol;

• central nervous system (CNS) depressants and stimulants, including barbiturates,anaesthetics, appetite suppressants, anticonvulsants and lamotrigine (with theexception of therapeutic doses of benzodiazepines used as hypnoinducers in patientsstabilised for more than one month since the screening visit);

• anticholinergic drugs; psychotropic drugs; anti-cholinesterase drugs,pyridostigmine;

• oral anticoagulants;

• chloramphenicol; rifampicin; zidovudine;

• loop diuretics; examination and vital signs at Visit 0 which in the opinion of the Investigator could interfere with the study procedures or endpoints evaluation.

4. Suspicious (according to the patient's symptoms at baseline) or confirmed COVID-19 infection at time of screening visit.
5. History of cervical, thoracic, or lumbosacral pain for ≥75% of the time in the last year, or any other LBP episode in the last 3 months that required pharmacological treatment with an opioid analgesic.
6. Patients with:

• serious spinal pathology; spinal surgery in the year prior to screening or history of more than one spinal surgery; history of severe lumbar spinal stenosis; ankylosing spondylitis; lumbosciatalgia; herniated disc or radiculopathy; severe arthritis and osteoporosis; muscular diseases, such as myositis, poliomyelitis, muscular dystrophy and myotonia; fibromyalgia; myasthenia grave; fracture or recent history of violent trauma of the back; structural deformity of the back;
• cancer, not in remission or in complete remission less than 1 year;
• active influenza or other viral syndrome; immunosuppression; systematically unwell; unexplained significant weight loss;
• women with polymenorrhea, endometriosis, ovarian cysts, uterine fibroids;
• widespread neurological symptoms (including cauda equina syndrome) or any brain disease; ever suffered from any brain damage or have been in a coma; epilepsy or seizures;
• active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration, or bleeding in the last 30 days;
• previous treatment with anticoagulants in the seven days before the screening visit;
• renal and/or hepatic failure;
• acute hepatitis;
• cardiac or pulmonary diseases;
• acetylsalicylic acid-triggered asthma;
• glucose-6-phosphate dehydrogenase-deficient patients; glutathione deficiency, dehydration, chronic malnutrition; anemia. Any other condition that, in the opinion of the Investigator, interferes with the study endpoints/procedures and does not justify the inclusion of the patient in the study.

7. Current use of full, regular, recommended doses of any skeletal muscle relaxants/non

• opioid analgesics/anti-inflammatory/NSAIDs in the 6 hours prior to the screening visit. Use is forbidden for the entire trial duration.

8. Current use of full, regular, recommended doses of or any medication that can alter the perception of pain (e.g., opioids, heparinoids, psychotropic agents, anti-H1 agents or glucocorticosteroids, etc.), in the 24 hours prior to the screening visit. Use is forbidden for the entire trial duration. Chronic intake of low doses of acetylsalicylic acid, i.e., ≤162 mg/daily, taken for at least 30 days prior to the first dose of study medication for non-analgesic reasons could be continued for the duration of the study.
9. Current use of the following medications (use is forbidden for the entire trial duration): • systemic corticosteroids;

• other drugs containing paracetamol;

• central nervous system (CNS) depressants and stimulants, including barbiturates, anaesthetics, appetite suppressants, anticonvulsants and lamotrigine (with the exception of therapeutic doses of benzodiazepines used as hypnoinducers in patients stabilised for more than one month since the screening visit);

• anticholinergic drugs; psychotropic drugs; anti-cholinesterase drugs, pyridostigmine;

• oral anticoagulants;

• chloramphenicol; rifampicin; zidovudine;

• loop diuretics;

• isoniazid; probenecid;

• propranolol;

• antiemetics;

• metoclopramide; domperidone;

• ion exchange resins (e.g. cholestyramine).

10. Patients undergoing physiotherapy, osteopathy or chiropractic treatments aimedto reduce LBP.

11. Patients treated with invasive procedures aimed to reduce LBP (e.g., epiduralinjections, spinal cord stimulation therapy).

12. History of alcoholic/substance abuse. Use of alcohol is forbidden during theentire duration of the study.

13. Inability to comply with the protocol requirements, instructions orstudy-related restrictions (i.e., uncooperative attitude, inability to returnfor study visits, unlikelihood of completing the clinical study); vulnerablepatients (i.e., persons kept in detention).

14. Patients involved in the conduct of the study (i.e., Investigator or his/herdeputy, first grade relatives, pharmacist, assistant or other personnel).

15. Participation to an interventional clinical trial within 3 months prior toVisit 0.