Phase III Randomized Double‑Blind Study of Fixed‑Dose Diclofenac Potassium + Thiocolchicoside Versus Diclofenac Potassium and Placebo in Acute Severe Low Back Pain

Primary objective: to evaluate the therapeutic superiority of the fixed‑dose combination of diclofenac potassium and thiocolchicoside versus diclofenac potassium (Cataflam®) and placebo in patients with acute severe low back pain, measured by the total sum of pain intensity differences (SPID) over 7 days, thereby assessing clinically relevant analgesic efficacy. Secondary objectives:

• Compare the average daily analgesic effect over the 7‑day treatment period across groups.
• Compare the cumulative use of rescue medication from baseline to day 7 between groups.
• Assess the proportion of patients achieving clinically meaningful pain relief (responders) by day 7.
• Compare safety and tolerability profiles of the investigational products throughout the study.
• Evaluate functional improvement from baseline to day 7 between treatment arms.

The trial enrolled adults of both sexes presenting with low back pain of acute onset (≤7 days) and severe intensity (≥75 mm on a visual analogue scale). Inclusion required participants to be ≥18 years of age, capable of understanding trial procedures, and able to attend scheduled follow‑up visits, with written informed consent obtained prior to any study‑related activity. Both male and female patients were eligible, and the population was defined by the acute pain condition rather than by other comorbidities, indicating otherwise typical health status aside from the index pain episode. No specific lifestyle factors such as diet or physical activity were stipulated in the selection criteria. The sponsor did not provide information on the total number of participants enrolled in the study.

The study is a multicenter randomized, double-blind, parallel-group Phase III therapeutic superiority trial that compares a fixed‑dose combination of diclofenac potassium plus thiocolchicoside with diclofenac potassium (Cataflam®) and two matching placebos in participants with acute severe low back pain. After an eligibility screening visit during which informed consent is obtained, baseline pain intensity (VAS), functional status (Finger‑to‑Floor Distance), and safety parameters are recorded, participants are allocated in a 1:1:1 ratio to test product, active comparator, or placebo. The assigned study medication is administered orally twice daily for seven days, and pain intensity is recorded at predefined intervals to calculate the primary endpoint, the cumulative time‑weighted sum of pain intensity differences (SPID) over the 0–6 hour post‑dose period for each of the seven treatment days. Follow‑up assessments occur on days 3 and 7, including evaluation of rescue medication use, responder status, adverse events, and functional improvement, with a final end‑of‑study visit on day 7 to repeat all baseline measurements. Participant involvement therefore spans approximately nine days, encompassing the screening, treatment, and end‑of‑study visits. Early termination may occur if a participant experiences a serious adverse event, demonstrates major protocol non‑compliance, withdraws consent, or requires prohibited concomitant therapy.

The investigational product is a fixed‑dose combination tablet containing diclofenac potassium and thiocolchicoside, marketed as Diclofenac + Thiocolchicoside / Verisfield tablets. The tablets are film‑coated and are administered orally. Each dose consists of two tablets; the exact dosing interval follows the study schedule but mirrors the regimen used for the active comparator.

The active control is CATAFLAM Sugar Coated Tablets 50 mg, which contain diclofenac potassium as a single active ingredient. The tablets are coated, administered orally, and each dose comprises three tablets, consistent with the protocol‑defined schedule.

Two matched placebos, identified as Placebo Yellow and Placebo Red, are provided to maintain blinding. The placebos are manufactured to resemble the active tablets in appearance and are administered orally in the same quantity and interval as the corresponding active treatment arm.

All participants may receive background analgesia with DEPON MAXIMUM 1000 mg film‑coated tablets, containing paracetamol. The background medication is taken orally, three tablets per dose, according to the stipulated rescue‑medication schedule.

Dosing is performed according to the randomized assignment with administration times recorded in the trial eCRF. Compliance is monitored through patient diaries, tablet counts at each visit, and verification of dosing timestamps in the electronic system. Missed or extra doses are documented, and protocol‑defined criteria guide the handling of non‑compliance.

Efficacy will be evaluated primarily by the cumulative, time‑weighted sum of pain intensity differences (SPID) calculated as the sum of daily SPID0‑6 h values over the 7‑day treatment period. Pain intensity will be recorded using a 100‑mm visual analog scale (VAS) before dosing and at regular intervals up to 6 hours post‑dose each day, and the differences will be integrated to obtain the daily SPID0‑6 h. The total SPID0‑6 h across days 0 to 6 will be compared between the fixed‑dose combination, the active comparator, and placebo groups.

Secondary efficacy assessments include: (1) the average analgesic effect, expressed as the daily SPID0‑6 h for each of the seven treatment days; (2) rescue medication use, measured as the mean number of rescue tablets taken per participant from baseline to day 7; (3) responder rate, defined as the proportion of patients achieving mild pain (VAS < 45 mm) by day 7; (4) functional improvement, quantified by the mean percent change in the Finger-to-Floor Distance test score from baseline to day 7; and (5) safety and tolerability, captured by the incidence of adverse events throughout the study. All secondary endpoints will be analyzed using appropriate statistical comparisons between treatment arms.