Comparative Efficacy and Tolerability of Intramuscular Diclofenac and Thiocolchicoside Versus Diclofenac in Acute Moderate to Severe Low Back Pain

The primary objective of this clinical trial is to confirm the superior **efficacy** of a combination intramuscular (IM) product containing **Thiocolchicoside** and **Diclofenac** compared to Diclofenac IM (Voltaren®) in patients with acute moderate to severe low back pain. This will be assessed by the relief of pain as reported by patients using a 10 cm visual analogue scale (VAS) at the Test of Cure visit, which occurs 3 hours post-administration of the investigational medicinal product. The clinical relevance of this objective lies in potentially providing a more effective treatment option for managing acute low back pain, which is a common and debilitating condition.

Secondary objectives include:

• Estimating the clinical improvement of muscle spasm, as assessed by the investigator, comparing the Test product to the Reference at the Test of Cure visit (3 hours post-administration).
• Estimating the relief of pain using the Test product compared to the Reference at the Intermediate visit, evaluated by VAS score 1 hour post-administration.
• Estimating the clinical improvement of muscle spasm at Visit 2, 1 hour post-administration.
• Investigating the safety and tolerability profile of the Test product compared to the Reference by assessing the occurrence of either topical or systemic adverse events (AEs).

The clinical trial focuses on evaluating the efficacy of a combination intramuscular product of **Thiocolchicoside** and Diclofenac in patients experiencing acute moderate to severe low back pain. The study population includes both male and female participants aged 18 years and older. Participants are required to present with acute low back pain that began within the last seven days and is of moderate to severe intensity, as indicated by a score of 50 mm or higher on a visual analogue scale. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must be able to comprehend the trial requirements and agree to attend follow-up visits. They must also provide voluntary written informed consent prior to any trial-related procedures. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include the ability to understand the trial requirements and willingness to provide informed consent, while exclusion criteria are not detailed in the provided data.

The clinical trial is designed as a **randomized**, multicenter, **double-blind**, two parallel group, Phase III study. It aims to compare the efficacy and tolerability of an intramuscular (IM) combination product of **diclofenac sodium** and **thiocolchicoside** against **diclofenac sodium** alone in patients experiencing acute moderate to severe low back pain. The trial is expected to commence recruitment on July 1, 2024, and conclude by January 2, 2025. Participants will be randomly assigned to receive either the test product or the reference product, with the primary objective being the assessment of pain relief using a 10 cm visual analogue scale (VAS) at the Test of Cure visit, which occurs 3 hours post-administration.

The study will include several visits, starting with a screening visit to confirm eligibility based on criteria such as age (≥18 years), recent onset of acute low back pain (≤7 days), and a VAS score of ≥50 mm. Participants must also be capable of understanding the trial requirements and willing to provide informed consent. Following the screening, participants will undergo baseline assessments before receiving the investigational medicinal product (IMP). Subsequent visits will include follow-up assessments at 1 hour and 3 hours post-administration to evaluate changes in VAS scores and other secondary endpoints, such as the proportion of patients achieving a >30% reduction in pain intensity and changes in finger-to-floor distance.

The expected duration of participant involvement is up to 2 days, aligning with the maximum treatment period. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any protocol deviations that compromise the integrity of the trial. The trial will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the confidentiality and safety of all participants throughout the study duration.

The clinical trial involves the administration of an experimental medication, **Diclofenac+Thiocolchicoside** solution for injection, which is a combination product containing the active substances **diclofenac sodium** and **thiocolchicoside**. This pharmaceutical form is a solution for injection intended for **intramuscular use**. The maximum daily dose is 6 ml, with a total maximum dose of 12 ml over a treatment period of up to 2 days. The medication is chemically derived and is not a pediatric formulation. The trial aims to assess the efficacy and tolerability of this combination product in patients with acute moderate to severe low back pain.

The comparator treatment in this study is **Voltaren**, a solution for injection containing the active substance **diclofenac sodium**. This medication is also administered via **intramuscular use**. The maximum daily dose for Voltaren is 150 mg, with a total maximum dose of 300 mg over a treatment period of up to 2 days. Voltaren serves as the reference product in this trial, providing a standard-of-care therapy against which the experimental combination product is compared. The secondary packaging of Voltaren has been modified for blinding purposes in the study.

Efficacy in this clinical trial will be assessed by comparing the combination intramuscular (IM) product of **Thiocolchicoside** and **Diclofenac** against Diclofenac IM (Voltaren®) in patients with acute moderate to severe low back pain. The primary endpoint for evaluating efficacy is the mean change in pain intensity, as measured by a 10 cm visual analogue scale (VAS), from baseline to 3 hours after administration of the investigational medicinal product (IMP). The VAS scoring range is 0–100, with assessments conducted at the Test of Cure visit, which occurs 3 hours post-administration.

Secondary endpoints include the mean change in VAS from baseline to 1 hour after administration, the proportion of patients achieving more than a 30% reduction in pain intensity from baseline at both 1 and 3 hours, and the mean change in Finger-to-floor distance from baseline to 1 and 3 hours post-administration. Additionally, the trial will monitor the proportion of patients withdrawn due to treatment-related reasons and those experiencing adverse events. These efficacy parameters will be collected and analyzed to determine the superior efficacy of the test product compared to the reference product.