Evaluation of Efficacy and Tolerability of Diclofenac, Orphenadrine, and Paracetamol Combination in Acute Severe Low Back Pain: A Phase III Randomized Controlled Trial

The primary objective is to demonstrate therapeutic superiority of the Fixed-Dose Combination of diclofenac, orphenadrine and paracetamol versus diclofenac monotherapy, the orphenadrine‑paracetamol combination, and placebo in patients with acute severe low back pain, as measured by the change in pain intensity from baseline to the final efficacy assessment (Visit 4). Secondary objectives include:

• Evaluation of early analgesic efficacy from baseline to Visit 3.
• Comparison of cumulative use of rescue medication through Visit 4 across treatment arms.
• Determination of the proportion of participants achieving clinically meaningful pain relief (responders) by Visit 4.
• Assessment of safety and tolerability profiles throughout the study period.
• Measurement of functional improvement using validated instruments at Visits 3 and 4.

The planned enrollment comprised adults aged 18–64 years of both sexes who presented with low back pain of acute onset (≤7 days) and severe intensity (≥75 mm on a visual analogue scale); participants had to be able to understand study requirements, provide voluntary written informed consent, and attend scheduled follow‑up visits. General health status beyond the acute pain episode was not further defined, and no specific lifestyle considerations such as diet, physical activity, or habits were stipulated. The sponsor did not provide information on the total number of participants enrolled.

The study is a Phase III, randomized, double‑blind, parallel‑group, placebo‑ and active‑controlled trial evaluating the therapeutic superiority of a fixed‑dose combination tablet containing diclofenac, orphenadrine and paracetamol versus the active comparators Cataflam® (diclofenac potassium) and Norgesic® (orphenadrine citrate + paracetamol) and matched placebos in patients with acute severe low back pain. After an initial screening visit to confirm eligibility (age 18–64 years, acute low back pain ≤7 days with VAS ≥75 mm), participants are randomized at baseline and receive one of the study treatments. Follow‑up assessments are scheduled at Visit 3 and Visit 4, during which the primary efficacy endpoint—mean percent change in Visual Analog Scale (VAS) pain score from baseline to Visit 4—is measured, along with secondary outcomes such as early pain response, rescue medication consumption, responder rate, safety/tolerability, and functional improvement using the Finger‑to‑Floor Distance test. The end‑of‑study visit coincides with Visit 4, completing the participant’s involvement from screening through final assessment. The overall trial recruitment period spans from September 30 2025 to March 31 2027.

The investigational product is a fixed‑dose combination tablet (Verisfield film‑coated tablet) containing diclofenac potassium, orphenadrine citrate, and paracetamol. The tablet is administered orally; the prescribed regimen is three tablets per day, taken at regular intervals with water. Each tablet delivers the specified amounts of the three active substances as defined in the product specification. Compliance is assessed by tablet count at each study visit and patient diary entries.

The first active comparator, CATAFLAM, consists of sugar‑coated tablets each containing 50 mg of diclofenac potassium. The tablets are taken orally, three times daily, with a dosing interval of approximately eight hours. Tablet accountability and patient‑reported dosing are used to monitor adherence.

The second active comparator, Norgesic, is a tablet formulation delivering 35 mg of orphenadrine citrate and 450 mg of paracetamol. Subjects receive six tablets per day, administered orally in divided doses. Compliance is verified through pill count and dosing logs maintained by the participant.

Two placebo preparations are utilized to maintain blinding: Placebo Red and Placebo White. Both are inert tablets matching the appearance of the active comparators and are administered orally in the same frequency and quantity as their respective active controls. Placebo compliance is monitored identically to active treatments.

Depon 500 mg tablets, containing paracetamol, are provided as background medication for rescue analgesia. The tablets are taken orally as needed, not exceeding the maximum daily dose outlined in the protocol. Rescue medication use is recorded in the study diary for safety and efficacy analyses.

Efficacy will be evaluated using pain intensity and functional mobility measurements. The primary efficacy parameter is the mean percent change in Visual Analog Scale (VAS) pain score from baseline to Visit 4. Secondary efficacy parameters include the mean percent change in VAS score from baseline to Visit 3 (early response), the mean number of rescue medication tablets consumed per participant from baseline to Visit 4, the proportion of patients achieving mild pain (VAS < 45 mm) by Visit 4 (responder rate), and the mean change in Finger-to-Floor Distance (FFD) test score from baseline to Visits 3 and 4.

VAS assessments will be performed using a validated 100‑mm scale at baseline, Visit 3, and Visit 4. Rescue medication use will be recorded daily by participants and summed for the interval from baseline to Visit 4. Responder status will be derived from VAS values obtained at Visit 4. Functional improvement will be measured with the FFD test, wherein the distance between the fingertip and floor is recorded at baseline, Visit 3, and Visit 4 using a standardized protocol. Data will be analyzed by calculating percent changes from baseline for VAS and absolute changes for FFD, and by summarizing rescue medication counts and responder proportions across treatment groups.