'OH Randomization Was Such That Approximately Equal HO Numbers of Patients Commenced Therapy with Both Preparations

Home , Fluperolone, Prednisolone acetate

Postgrad Med J: first published as 10.1136/pgmj.39.449.159 on 1 March 1963. Downloaded from

March I963 DALY, NELSON and ROSE: Hyponatracmia with Carcinoma of the Bronchus 159 REFERENCES ALLOTT, E. N., and SKELTON, M. 0. (I960): Increased Adrenocortical Activity Associated with Malignant Disease, Lancet, ii, 278. BAGSHAWE, K. D. (ig6oa): Hypokalsemia, Carcinoma and Cushing's Syndrome, Ibid., ii, 284. (ig6ob): Hyperfunction of the Adrenal Cortex with Adrenal Metastases, Ibid., ii, 287. REES, J. R., ROSALKI, S. B., and MACLEAN, A. D. W. (I960): Hyponatrsemia and Impaired Renal Tubular Function with Carcinoma of Bronchus, Ibid., ii, IOO5. ROBERTS, H. J. (1959): The Syndrome of Hyponatremia and Renal Sodium Loss Probably Resulting from Inappro- priate Secretion of Antidiuretic Hormone, Ann. intern. Med., 51, 1420. SCHWARTZ, W. B., BENNETT, W., CURELOP, S., and BARTTER, F. C. (1957): A Syndrome of Renal Sodium Loss and Hyponatrxemia Probably Resulting from Inappropriate Secretion of Antidiuretic Hormone, Amer. J. Med., 23, 529. , TASSELL, D., and BARTTER, F. C. (I960): Further Observations on Hyponatrmmia and Renal Sodium Loss Probably Re3ulting from Insppropriate Secretion of Antidiuretic Hormone, New Engl J. Med., 262, 743. TURNER, P., and WILLIAMS, R. (I962): Unexplained Steatorrhoea in the Syndrome of Hyponatreemia and Carcinoma of Bronchus, Brit. med. J7., i, 287.

Clinical Trial

A CLINICAL TRIAL OF FLUPEROLONE: A NEW TOPICAL STEROID by copyright. NAPIER THORNE, M.D., M.R.C.P. Physician-in-Charge, Skin Departments, Prince of Wales's General Hospital, Mile End Hospital, and St. Andrew's Hospital, Bow.

FOR the evaluation of a new topical steroid, flupero- patient was unaware that the second preparation lone (P-I742: Methral; Pfizer) a clinical trial was was of a lower concentration than the original. planned in four phases. First, in order to obtain a Chemically this compound is of interest both due

clinical impression, ointments of both 0.25% and to inclusion of a fluorine atom, and to the modi- http://pmj.bmj.com/ i.o% and'spray pack preparations, were used for the fication of one of the side chains by the introduction treatment of a variety of commonly occurring of a methyl grouping at position C21. The structure dermatoses. Secondly, following encouraging of fluperolone can be described as 2I-methyl-g9 results from this pilot trial and favourable reports flouro-prednisolone acetate (Fig. I). from another centre (Sneddon, I962), a double blind comparative trial was undertaken with preparations containing either 0.25% fluperolone or I.o% O CH hydrocortisone. Both were of identical appearance ,, I 3 and consistency, and were dispensed in a water H C-C-O-CH, on September 30, 2021 by guest. Protected miscible base. In this phase of the trial. patients 3 1 were given, in a blind, random manner, one of the C =0 two preparations, but at the first follow-up visit after one week, the preparation was changed. The /'OH randomization was such that approximately equal HO numbers of patients commenced therapy with both preparations. The third phase of this trial was also F a double blind study, planned in an identical manner, but comparing o. i % fluperolone and i .o% hydrocortisone. Lastly, in the fourth phase, patients with various types of eczema were treated with o.i% fluperolone but at the first follow-up visit the preparation was changed to o.oi % fluperolone, to see whether this low concentration would be o / adequate to maintain the improvement observed FIG. I.-Fluperolone: note inclusion of fluorine atom during treatment with the o.i% preparation. The at Cg and methyl group at position C21. Postgrad Med J: first published as 10.1136/pgmj.39.449.159 on 1 March 1963. Downloaded from x6o POSTGRADUATE MEDICAL JOURNAL March 1903

Animal studies (Llaurado and Schneider, I 960) TABLE 3 had already demonstrated that this steroid possessed potent anti-inflammatory activity. No. of Equal Superior Preparation Cases Response Total Results o.i% fluperolone 3 I 9 A total of 66 patients were included in the four i.o% hydrocortisone 5 phases of these trials. In the initial clinical evaluation there was a total of 38 patients treated as shown in Table tions, O.I% fluperolone having a directly compar- i. able effect to i.o% hydrocortisone. TABLE I The fourth part of this trial included fifteen patients, all suffering from various types of eczema. Phase i: Clinical Evaluation Of these fifteen, two patients were so improved after treatment with the O.I% fluperolone that no No. of Much further treatment was necessary. Of the remainder, Fluperolone Patients Improved No five showed an improvement that was maintained Preparation Treated or Improved Change with the o.oi % preparation, one showed an improvement only with the lower concentration, three i.o% ointment 14 13 I showed no change with either preparation, and 0.25% ointment IO 8 2 I.0o% followed four showed an initial improvement with o.I% byo.25% .. 4 4 - fluperolone, but there was some deterioration on Spray pack changing to O.0i% (Table 4). preparation 10 10 - TABLE 4 Total .... 38 35 3 Fluperolone No. of Cases The impression gained was that fluperolone O.I% | .OI% showed obvious potent anti-inflammatory activity, by copyright. and that pruritus was relieved more 2 Cured Not used rapidly with 5 Improved Improvement fluperolone than would be expected with hydro- maintained cortisone. From previous clinical experience of I No improvement Improved trials with topical steroid ointment it was considered 3 No change No change that the 0.250/o preparation was at least as effective 4 Improved Slight deterioration as, or possibly slightly superior to, i.o%O hydrocortisone. TOTAL 15 The second phase of this trial, a blind comparative study of 0.25% fluperolone and i.o% hydro- As a result of these cortisone, gave results as shown below (Table 2). various investigations it can be concluded that o. I0% fluperolone is as effectivelhttp://pmj.bmj.com/ as I.0% hydrocortisone in the treatment of a wide TABLE 2 variety of dermatological conditions. Superior Preparation In particular throughout this trial, it was No. of Cases Total observed that pruritus was relieved more rapidly 0.25% fluperolone 5 with fluperolone than with hydrocortisone. i .o% hydrocortisone . . 10 Summary A clinical trial, in four phases,

demonstrates the on September 30, 2021 by guest. Protected Thus this phase shows both to be equally effec- efficacy of a new topical steroid preparation, tive, in these cases. fluperolone, in the treatment of various dermatoses. Phase three of the trial, comparing o. i % flupero- Fluperolone at O.I% concentration is comparable lone and i .o% hydrocortisone, gave the following in efficacy to i.o%O hydrocortisone, and clinical results (Table 3). evidence demonstrates that the fluperolone relieves Thus again, in this small series, there is little to pruritus more rapidly than hydrocortisone, and has choose between the efficacy of these two prepara- a quicker onset of action. REFERENCES LLAURADO, J. G., and SCHNEIDER, J. A. (I960). A New Family of Steroids with Strong Anti-Inflammatory Activity. Fed. Proc. I9, I 59. SNEDDON, I. B. (I962). Personal Communication.