Summary of therapeutic equivalence study results for Darfen Gel, gel (ibuprofen and levomenthol)
17 February 2023Objective. To evaluate the comparative efficacy (therapeutic equivalence) and safety of medicinal products (MPs) Darfen Gel, gel (PrJSC “Pharmaceutical Firm “Darnitsa”, Ukraine) and Deep Relief, gel (The Mentholatum Company Limited, United Kingdom) in patients with pain due to primary osteoarthritis of а knee joint of stage II–III according to the Kellgren-Lawrence classification in a multicenter, randomized, open-label study of therapeutic equivalence. Study code: IBF01-T.
Objects and methods of the study. The study included outpatients, male or female, aged 45 years and older, and diagnosed with primary knee osteoarthritis. Patients were randomized if the disease was accompanied by pain in the target knee joint at rest with the intensity of ≥ 40 mm on 100-mm visual analogue scale and ≥ 15 points on “Pain” subscale of the KOOS questionnaire, and there was a need in topical non-steroidal anti-inflammatory drugs. For 14 days, study subjects were using one of the study MPs (test MP Darfen Gel in the main group and reference MP Deep Relief in the comparison group) by skin application followed by gentle rubbing three times a day. One gram of each study gel contains 50 mg of ibuprofen and 30 mg of levomenthol.
Treatment efficacy (i.e., a primary endpoint of the study) was assessed after 14 days of MP use according to the Outcome Measures for Arthritis Clinical Trials (OMERACT) of Osteoarthritis Research Society International (OARSI) using “Pain”, “Function, Daily Living” and “Quality of Life” scales of the KOOS questionnaire.
The conclusion about safety of the MPs was made based on objective data, blood count and blood chemistry tests, urinalysis, electrocardiography results and monitoring of side effects during MP use.
Results. 163 patients who voluntarily agreed to participate in the clinical study were enrolled and screened. Based on the results of the screening, 160 patients met all inclusion criteria and none of the exclusion criteria, and the patients were evenly distributed into the main or comparison group of 80 patients each.
Therapeutic equivalence of the developed product Darfen Gel, gel, to the reference product Deep Relief, gel, was assessed based on data from 137 patients who completed the study according to the study protocol (PP population): 69 patients in the main group and 68 in the comparison group.
The proportion of patients in whom the study treatment was effective according to the OARSI OMERACT criteria (i.e., responder rate) was 62.3% in the main group and 60.3% in the comparison group. The difference in proportions was 2.0% (95% confidence interval: -14.31%; 18.31%). Since the lower limit of the confidence interval (-14.31%) exceeds the lower limit of the equivalence zone (- 20%) and the upper limit of the confidence interval (18.31%) is lower than the upper limit of the equivalence zone (20%), the test product Darfen Gel, gel, is therapeutically equivalent to Deep Relief, gel.
The safety analysis included data from 160 patients who received at least one dose of the study drug. Based on the assessment results of physical, laboratory and instrumental parameters in the dynamics, no statistically significant changes were found in both groups (main and comparison).
During the study, one mild adverse reaction was reported in the form of a rash, redness and itching at the administration site of the reference product. There were no serious adverse reactions/adverse events.
Conclusion. The present study proved the therapeutic equivalence of Darfen Gel, gel to the reference product Deep Relief, gel. Both study drugs were characterized by good tolerability when used for 14 days in patients with primary osteoarthritis of the knee joint.
Additional information. This study was conducted in accordance with the requirements of Good Clinical Practice (GCP) and the ethical principles of the Declaration of Helsinki. Permission to study conduct was provided by the Ministry of Health of Ukraine (order dated 04.12.2019 No. 2372).