Evaluation of the Efficacy of Diclofenac Sodium and Thiocolchicoside Combination Versus Diclofenac Sodium and Placebo in Acute Moderate-Severe Low Back Pain
- Trial ID
- 2024-518753-42-00
- Protocol
- EPDICTIO75+4F01-2022
- Sponsor
- Epifarma S.r.l.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **superiority** of a fixed combination of diclofenac 75 mg and thiocolchicoside 4 mg administered via intramuscular injection over the reference diclofenac 75 mg intramuscular injection and placebo in alleviating pain symptoms in adult patients with acute moderate-severe **low back pain** (LBP). This assessment will be conducted 48 (±2) hours after the initiation of treatment, which involves two intramuscular injections on Day 1 and Day 2 of all investigational medicinal products. The efficacy will be evaluated using a 100-mm Visual Analog Scale (VAS) for pain assessment. This is clinically relevant as LBP is a prevalent and disabling condition, and effective pain management is crucial for improving patient mobility and quality of life.
The secondary objectives of the study include:
- Comparing the efficacy of the test, reference, and placebo groups in terms of pain symptoms (VAS for pain) at various daily time points up to 7 days from treatment initiation.
- Evaluating the proportion of responder patients after 48 hours (Day 3) and 7 days (Day 7) from treatment start.
- Assessing muscle contracture using the Schober index.
- Measuring disability due to LBP with the Roland Morris disability questionnaire.
- Monitoring the consumption of rescue medication (oral diclofenac 50 mg tablet).
- Assessing the tolerability and safety of the investigational medicinal products through summaries of adverse events, treatment discontinuation due to adverse events, laboratory evaluations, electrocardiograms (ECGs), and vital signs (sitting heart rate, sitting systolic/diastolic blood pressure, respiratory rate, body temperature).
Participants
The clinical trial focuses on adult patients experiencing **acute low back pain** (LBP), a prevalent and disabling condition. The study population includes both male and female participants aged 18 years and older, with no specific upper age limit provided. Participants are required to have moderate to severe intensity of back pain, as indicated by a Visual Analog Scale (VAS) score of 50 mm or higher. The trial does not involve a vulnerable population. Participants must be in satisfactory general health as assessed by the investigator, based on medical history and physical examination. Female participants of child-bearing potential are required to use highly effective birth control methods and must have a negative pregnancy test prior to the study. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants have stable muscle contracture and understand the study procedures, providing informed consent to participate. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, parallel-group study with active and placebo controls to evaluate the efficacy of a fixed combination of **diclofenac sodium** 75 mg and **thiocolchicoside** 4 mg administered via intramuscular injection. The trial aims to demonstrate the superiority of this combination over a reference treatment of diclofenac 75 mg and placebo in relieving pain symptoms in adult patients with acute moderate to severe low back pain (LBP). The study will utilize a 100-mm Visual Analog Scale (VAS) to assess pain relief efficacy after 48 hours from the start of treatment, with two intramuscular injections administered on Day 1 and Day 2.
The trial is expected to last until March 31, 2025, with participant recruitment starting on May 22, 2023. Participants will be involved in the study for a maximum of 7 days, with the primary endpoint being the sum of pain intensity difference (SPID) from baseline to Day 3. Secondary endpoints include changes in muscle contracture, proportion of responders, and use of rescue medication. Safety endpoints will monitor adverse events, laboratory parameters, electrocardiograms, and vital signs.
Study visits will include an initial screening visit to confirm eligibility based on criteria such as age, acute LBP status, and general health. Follow-up visits will occur on Day 3 and Day 7 to assess pain relief, muscle contracture, and any adverse events. The end-of-study visit will evaluate overall treatment efficacy and safety. Participants may be terminated early from the study if they experience significant adverse events or require rescue medication within 48 hours of treatment initiation. The trial will ensure that all participants provide informed consent and adhere to the study protocol throughout their involvement.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The **experimental medication** is a fixed combination of **diclofenac sodium** 75 mg and **thiocolchicoside** 4 mg, formulated as a solution for injection. This medication is provided in a vial for intramuscular use. The maximum daily dose is 4 mL, with a total maximum dose of 8 mL over a treatment period of 2 days. The administration route is intramuscular, and the medication is classified under centrally acting agents, specifically thiocolchicoside combinations. The product is manufactured by EPIFARMA and is not a paediatric formulation.
The **comparator treatment** in the study is **VOLTAREN**, which contains **diclofenac sodium** 75 mg/3 mL as a solution for injection. This non-steroidal anti-inflammatory and antirheumatic product is administered intramuscularly. The maximum daily dose is 75 mg, with a total maximum dose of 150 mg over a 2-day treatment period. The product is manufactured by NOVARTIS IRELAND LIMITED and is not a paediatric formulation.
The **placebo** used in the study is **water for injection**, which serves as a solvent for parenteral use. It is administered intramuscularly with a maximum daily dose of 3 mL and a total maximum dose of 6 mL over a 2-day treatment period. This product is not a paediatric formulation and is used to maintain the double-blind nature of the study.
Additionally, **diclofenac** in tablet form is used as an **auxiliary treatment**. This non-steroidal anti-inflammatory and antirheumatic product is administered orally. The maximum daily dose is 150 mg, with a total maximum dose of 1200 mg over an 8-day treatment period. This product is not a paediatric formulation and serves as a supportive treatment in the study.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the use of a 100-mm Visual Analog Scale (VAS) for the evaluation of pain in patients with acute moderate-severe low back pain. The primary efficacy endpoint is the sum of pain intensity difference (SPID) from baseline to Day 3, with measurements taken every 12 hours (two in the morning and two in the evening). Pain intensity difference (PID) from baseline is calculated by subtracting each pain intensity score from the baseline score, and the overall SPID is used to evaluate the primary efficacy endpoint.
Secondary efficacy endpoints include changes from baseline to Day 3 and Day 7 in muscle contracture, as measured by the Schober index, and the SPID based on daily VAS measurements for pain up to 7 days from the start of treatment. The proportion of responder patients, defined as those with a decrease in VAS for pain of at least 50% from baseline, will be assessed after 48 hours and 7 days. Additional secondary endpoints include changes in disability due to low back pain, as measured by the 24-item Roland Morris disability questionnaire, and the use of rescue medication, including the number and percentage of users, number of days with use, and number of tablets used up to Day 3 and Day 7. The time elapsed from the first study drug administration to the first intake of rescue medication will also be recorded.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and female patients aged ≥ 18 years; 2. Patients with acute LBP at the moment of initiating treatment; LBP is defined as pain initiating from the area below the tips of the scapulae and above the buttocks, with onset no more than 12 weeks prior to the screening visit; 3. Back pain of moderate to severe intensity, defined as ≥ 50 mm at VAS; 4. Patients with stable muscle contracture; a muscle contracture is defined as an increase < 5 cm in the distance between the two fingers of the examiner in the Schober test performed at the screening visit; 5. If female and of child-bearing potential, the patient must use a highly effective method of birth control during the study treatment period and until one month after the end of treatment. Highly effective birth control methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence; 6. If female and of child-bearing potential, the patient must be non-nursing and should not become pregnant throughout the whole study duration; all females of child-bearing potential must have a negative urine pregnancy test prior the first administration. A childbearing potential female is defined as a fertile female, following menarche and until becoming post-menopausal unless permanently sterile (permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause; 7. Satisfactory general health status as determined by the Investigator based on medical history and physical examination; 8. Patients must understand and provide written informed consent before they can participate in the study. They must understand the study procedures of the trial, and be willing to complete the required assessments.
- If male patient, the patient must use an effective method of birth control during the study treatment period and until three months after the end of treatment. Effective birth control methods include: permanent sterilization methods (i.e. vasectomy); sexual abstinence; use of condom with spermicide.
Exclusion Criteria
- Patients with symptoms that might be attributable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) at inclusion and in the 48 hours preceding the inclusion in the study or contact with subjects positive to SARS-CoV-2 in the 48 hours preceding the inclusion in the study; 2. Patients with a history of cervical, thoracic, or lumbosacral pain for ≥ 50% of the time in the year prior to screening; 3. Patients with presence of lumbosciatalgia; 4. Patients with a history of any LBP episode, except the current acute episode, within 3 months prior to screening that was associated with disability, or required treatment with an opioid analgesic; 5. Patients with acute LBP caused by a serious or malignant condition; 6. Patients with acute LBP of traumatic origin; 7. Patients with acute LBP of infective origin; 8. Patients with acute LBP caused by a rheumatic disease; 9. Patients on treatment with anticoagulant agents; 10. Patients who underwent spinal surgery in the year prior to screening or had a history of more than one spinal surgery; 11. Patients who had a history of severe lumbar spinal stenosis, fibromyalgia, or ankylosing spondylitis; 12. Patients with a medical history of seizures; 13. Pregnancy or lactation period; 14. Women with childbearing potential who are not using highly effective methods of birth control to avoid pregnancy and who are not willing to use highly effective methods of birth control until one month after the end of the treatment; 15. Women with polymenorrhea; 16. History of alcohol or drug abuse; 17. History of allergy or hypersensitivity or intolerance to diclofenac or thiocolchicoside, and/or to active or inactive excipients of the used IMPs formulations; 18. Known hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs); 19. Use of non-steroid anti-inflammatory drugs (e.g. acetyl salicylic acid) and analgesics (with the exception of diclofenac) in the week before the entry in the study. Chronic intake of small doses of acetylsalicylic acid (≤ 162 mg/daily) taken for at least 30 days prior to the first dose of study medication for non-analgesic reasons may be continued for the duration of the study; 20. Use of diclofenac in the 12 hours preceding entry in the study; 21. Use of any other treatment or medication that can alter the perception of pain (e.g. heparinoids, opioids, psychotropic agents, anti H1 agents or analgesics like glucocorticosteroids, NSAIDs, etc.) for the same indication or other indications (e.g. rheumatoid arthritis) in the week before the entry in the study; 22. Use of diuretic agents in the 30 days preceding entry in the study; 23. History of active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration or bleeding within 30 days preceding screening; 24. History of uncontrolled chronic or acute concomitant disease which, in the Investigator’s opinion, would contraindicate study participation or confound interpretation of the results. In particular, patients with any of the following diseases should be excluded from participation: overt congestive heart failure (NYHA class II-IV), ischemic heart disease, peripheral arterial disease and/or cerebral vascular disease, severe liver or renal impairment, alterations of haematopoiesis; 25. Patients in which the administration of the IMP is contraindicated, such as in case of flaccid paralysis and muscular hypotonia; 26. Participation in any other clinical study or investigation within 30 days prior to the screening or use of any investigational product within a period of more than 5 half-lives, whichever is longer.
- Males who are not willing to use effective methods of birth control until three months after the end of treatment.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Recruiting | 22 May 2023 | 96 |
 Italy | Not Recruiting | 22 May 2023 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
WATER FOR INJECTION | Placebo | — | INTRAMUSCULAR | 3 | 2 | SUB12398MIG |
VOLTAREN 75mg/3mL solution for injection. | Comparator | SOLUTION FOR INJECTION | INTRAMUSCULAR | 75 | 2 | PRD6278180 |
DICLOFENAC | Other | — | ORAL | 150 | 8 | SUB07092MIG |
Diclofenac Sodium 75 mg + Thiocolchicoside 4 mg/ 4 ml solution for injection for intramuscular use | Test | VIAL FOR INTRAMUSCULAR USE | INTRAMUSCULAR | 4 | 2 | PRD11665347 |