A multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group comparison of diclofenac-K and ibuprofen for the treatment of adults with influenza-like symptoms.
BACKGROUND
The alleviation of influenza-like symptoms, such as fever, headache, and muscle/joint aches and pains, is important so that sufferers can return to their normal daily activities. A flexible dosing regimen is proposed, starting with an initial dose of 2 tablets (2 x 12.5 mg), followed by 1 to 2 tablets every 4 to 6 hours as needed, to a maximum daily dose of 75 mg for up to 3 days for fever and 5 days for pain. This flexible dosing regimen matches the existing over-the-counter dosing regimen of ibuprofen, which allows the patient to adjust the treatment according to the type, duration, and severity of symptoms.


OBJECTIVE
This study assessed the efficacy and tolerability of diclofenac-K 12.5 mg versus ibuprofen 200 mg and placebo against influenza-like symptoms (oral temperature > or = 38.1 degrees C, and at least moderate headache and muscle/joint aches and pains).


METHODS
This was a 3-day, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial conducted in Germany. The flexible dosing regimens comprised 2 tablets of diclofenac-K (12.5 mg), ibuprofen (200 mg), or placebo, then 1 to 2 tablets every 4 to 6 hours as needed, to a maximum of 6 tablets/d. Primary efficacy outcomes were fever reduction after the initial dose and an end-of-study global assessment of overall symptom relief. Secondary efficacy outcomes included reduction of feverishness; relief of headache; and relief of muscle/joint aches and pains, after the first dose and at the end of days 1, 2, and 3. Use of rescue medication (paracetamol 500-mg tablets) and usage patterns of study medication were also studied. Tolerability was monitored by recording of patients' adverse events.


RESULTS
A total of 356 patients were enrolled (n = 121, 120, and 115 patients in the diclofenac-K, ibuprofen, and placebo groups, respectively). All patients were white except 1 Asian patient in the diclofenac-K group; 55% to 60% of patients in all 3 groups were male; the mean age in each treatment group was approximately 40 years. At baseline, mean oral temperature ranged from 38.65 degrees C in the placebo group to 38.74 degrees C in the diclofenac-K group. Mean oral temperatures in both active groups were significantly lower than that of the placebo group from 30 minutes through 6 hours (P < 0.001), dropping 0.85 degrees C after 4 hours in the diclofenac-K group and 0.76 degrees C in the ibuprofen group versus 0.32 degrees C for placebo. In the end-of-study global treatment assessment, 89.0% of diclofenac-K and 89.1% of ibuprofen patients rated global efficacy as "good" to "excellent" versus only 32.1% for placebo. Diclofenac-K was superior to placebo (P < 0.001) and similar to ibuprofen on all direct assessments of fever and aches and pains. Both active treatments were as well tolerated as was placebo.


CONCLUSIONS
In this 3-day study, diclofenac-K 12.5 mg taken in a flexible dosing regimen was more effective than placebo in relieving influenza-like symptoms, with comparable tolerability Efficacy and tolerability of diclofenac-K were similar to those of ibuprofen 200 mg.
Grebe
Wolfgang
W
Novartis Consumer Health SA, Nyon, Switzerland.
Ionescu
Elisabeta
E
Gold
Morris S
MS
Liu
Jiun-Min H
JM
Frank
William O
WO
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000188:drug therapy*; D006261:Headache / Q000188:drug therapy*; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D007251:Influenza, Human / Q000188:drug therapy; D008297:Male; D010146:Pain / Q000188:drug therapy*; D013577:Syndrome; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D007052:Ibuprofen