BritishJournal of Dermatology (1983) 1091 63-65.
`
`A double-blind study of I% metronidazole cream
`versus systemic oxytetracycline therapy
`for rosacea
`
`P.G.NIELSEN
`Department of Dermatology, Centrat Hospital, S-961 85 Boden, Sweden
`
`Accepted for publication 2 November 1982
`
`SUMMARY
`In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months
`with either r% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets
`taken twice daily, and placebo cream (the cream base). The patients were assessed before and at
`the end of the trial, using the following criteria: (I) overall clinical assessment, (2) lesion counts,
`(3) degree of erythema, (4) independent photographic evaluation, (S) patients' opinion. An
`improvement was shown in 90% of the patients of both groups, and there was no significant
`difference between the two treatments.
`
`One per cent metronidazole cream has been shown tobe significantly better than a placebo
`cream in the treatment of rosacea (Gamborg Nielsen, 1983a). It was therefore considered
`important to compare the cream with conventional therapy, and for this reason a double-blind
`study of 1% metronidazole cream versus a daily dose of soo mg oxytetracycline was performed.
`
`METHODS
`Fifty-one randomly selected patients (thirty-four warnen and seventeen men, average age 44
`years) with rosacea entered the trial, which took place during March, April and May of 1982.
`None of the patients had been treated with drugs active against rosacea during the 3 months
`preceding the start of the trial.
`Patients were assigned at random to one of the two courses of treatment. Twenty-five were
`allocated to I% metronidazole cream and placebo tablets and twenty-six to oxytetracycline
`tablets 250 mg twice daily, and placebo cream.
`Patients were provided with 50 g of the test cream, which was applied once daily for 2 months.
`The cream base used for both the placebo and the metronidazole cream was an oil in water
`emulsion (lactic acid r·s%, sodium lauryl sulphate o·S%, cetylane s%, cetanole 15% and
`ooo7-0963/83/07oo-oo6)$02.oo © 1983 British Association of Dermatologists
`63
`
`Dr. Reddy's Laboratories, Ud., et al.
`V.
`Galderma Laboratories, lnc.
`IPR2015-__
`Exhibit 1009
`
`Exh. 1009
`
`

`
`P.G.Nielsen
`distilled water So%). Tablets were administered twice daily 30 min before meals. None ofthe
`patients were allowed to use any other treatment for their rosacea during the study period.
`Before and at the end of the trial each patient underwent an overall clinical examination.
`including lesion counts (papules, pustules and telangiectases) and degree of erythema; this was
`combined with standardized photographic evaluation of the rash ( Garnborg Nielsen, 1983 b ). At
`the end ofthe trial the patients, subjective opinion ofthe treatmentwas registered. Patients were
`examined for side-effects and special attention was paid to possible allergic or irritant reactions
`to the cream.
`
`RESULTS
`Twenty-five patients receiving I% metronidazole cream, and twenty-three receiving oxytetra-
`·cyclines completed the study. Two patients became pregnant during the study period (they
`stopped treatment and were excluded) and one left without reason. All three were from the
`oxytetracycline group. The results of the overall clinical assessment and photographic
`evaluation showed that there was no significant difference between the two courses oftreatment
`(Table I). Reduction of erythema, papules and pustules was the samein both groups, and the
`number and extent of telangiectases were unchanged. No side-effects were reported in either
`group.
`
`TABLE 1. Number of improved patients in the metronidazole
`and oxytetracycline groups assessed by clinical estimation,
`photographic evaluation, and subjective opinion of treatment
`results
`
`1% Metronidazole
`cream
`
`Oxytetracycline
`(500 mg)
`
`Objective
`Clinical
`Photographie
`
`Subjective
`Patients' opinion
`
`24/25 (96%)
`21/25 (84%)
`
`22/23 (96%)
`21/23 (91%)
`
`22/25 (88%)
`
`ZI/23 (91%)
`
`DISCUSSION
`In several publications it has been shown that orally administered metronidazole is an: effective
`treatment for rosacea (Pye & Burton, 1976; Schirner & Haneke, I98I), and also that response to
`such treatment is as good asthat with oxytetracycline (Saihan & Burton, I98o). Recently we
`have shown that in rosacea topical application of metronidazole is significantly better than
`placebo. In the present study it was demonstrated that response to this cream does not differ
`significantly from that produced by systemic oxytetracycline. It has been shown that
`transcutaneous absorption from I% metronidazole cream results in a blood l~vel that is at most
`r 'Yo of the Ievel reached when the minimum oral dose necessary for improvement of rosacea is
`administered (Arnold, I982). Thus fewer systemic side-effects would be expected and we found
`none.
`
`Exh. 1009
`
`

`
`Rosacea therapy
`
`ACKNOWLEDGMENTS
`Coded tabletsandtest creams were kindly provided by A/S Dumex, Copenhagen.
`
`REFERENCES
`ARNOLD, E. (1982) Metronidazole cream I%, serum koncentrationer ved behandling af rosacea. Biologkai Department,
`Dumex Ltd., unpublished.
`GAMBORG NIELSEN, P. (1983a) Treatment of rosacea with x% metronidazole cream. A double-blind study. British
`Journal of Dermatology, toS, 327.
`GAMBORG NIELSEN, P. (1983b) A photographic aid in the objective assessment of rosacea. Archives of Dermatology, in
`press.
`PYE, R.J. & BuRTON, J.L. (1976) Treatment ofrosacea by metronidazole. Lancet, i, I2II-I2I2.
`SAIHAN, E.M. & BURTON, J.L. (1980) A double-blind trial ofmetronidazole versus oxytetracycline therapy for rosacea.
`British Journal of Dermatology, 102, 443-444·
`ScHIRNER, A. & HANEKE, E. (1981) Rosacea and metronidazole. Acta Dermatologica, 7, 27-30.
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`Exh. 1009