SYSTEMIC ENZYME SUPPORT.org

Name of Sponsor/Company:
MUCOS Pharma GmbH & Co.
Malvenweg 2, D-82538 Geretsried

Individual Study Table Referring to Part at the Dossier

(For National Authority Use Only)

Name of Finished Product:
Phlogenzym^®

Volume:

Name of Active Ingredient(s):
Trypsin, Bromelin, Rutosid

Page:

Title of Study:
Phlogenzym^® in the Treatment of a Monoarticular Gonarthritis

Investigator(s):
Prim. Prof. Gert Klein, M.D., Rehabilitation Center for Rheumatic Diseases and Diseases of the Cardiovascular System, Thorerstrasse 26, A-5760 Saalfelden, Austria

Study centre(s):
Prim. Prof. Gert Klein, M.D., Rehabilitation Center for Rheumatic Diseases and Diseases of the Cardiovascular System, Thorerstrasse 26, A-5760 Saalfelden, Austria

Publication (reference/s):

Studied period (mo/years): 1 year
(date of first enrolment) June 18^th, 1996
(date of last completed) July 21^st, 1997

Phase of development:
Phase III

Objectives:
To test efficacy and tolerance of Phlogenzym as compared with the NSAID diclofenac for equivalence.

Methodology:
Double-blind, randomized study with two parallel groups.
Measurements of clinical signs and symptoms.

Number of patients (planned and analysed):
72 planned, 73 included, 73 evaluated.

Diagnosis and main criteria for inclusion:
Monoarticular activated, painful gonarthritis; Lesquesne index > 10.0.

Test product, dose and mode of administration, batch number:
Phlogenzym^® (48mg trypsin, 90mg bromelin, 100mg rutosid x 3 H₂O,
2 tablets orally t.i.d. (i.e., 6 tbl. per day), batch no.: 951184;
Placebo tablets, batch no.: 750398

Duration of treatment:
3 weeks; follow-up 4 weeks later

Reference therapy, dose and mode of administration, batch number.
Diclofenac 50 mg, 1 tablet t.i.d. (i.e., 3 tbl. per day) during first week, 1 tbl. b.i.d. (i.e., 2 tbl. per day) during second and third week; batch no.: 960591;
diclofenac placebo tablets, batch no.: 967806

Name of Sponsor/Company:
MUCOS Pharma GmbH & Co.
Malvenweg 2, D-82538 Geretsried

Individual Study Table Referring to Part at the Dossier

(For National Authority Use Only)

Name of Finished Product:
Phlogenzym^®

Volume:

Name of Active Ingredient(s):
Trypsin, Bromelin, Rutosid

Page:

Criteria for evaluation
Efficacy: Main endpoint was the Lesquesne index and the sum score of pain and restricted movement 4 weeks after end of therapy; secondary endpoints were single pain symptoms, global judgement.
Safety: Global judgement of tolerance (by physician and patients); laboratory parameters; adverse events

Statistical methods:
To test comparability of groups: Wilcoxon-Mann-Whitney (two-tailed);
to test equivalence of the groups: Wilcoxon-Mann-Whitney (one-tailed);
to test difference in number of adverse events: Fisher's exact test (two-tailed).

SUMMARY - CONCLUSIONS
EFFICACY RESULTS:
The main endpoint Lesquesne index 4 weeks after end of therapy has shown proven equivalence between the two treatment arms. The Mann-Whitney statistic (0.5459) and the lower bound of the 95% confidence interval (0.4568) were above the limit for equivalence (0.44). Also if tested at end of therapy, both groups were equivalent (statistics: 0.5308, LB of 95%-Cl: 0.4458). The areas under the curve were both equivalent, until 4 weeks after end of therapy and until end of therapy (LB 95%-CI: 0.4664, and 0.4610, resp.).
The second main endpoint, the sum score of symptoms 4 weeks after end of therapy, also proved significantly for equivalence: the LB of the 95%-CI was with 0.4608 above the limit (0.44).
SAFETY RESULTS:
No differences between the groups in the global judgement of tolerance nor in the frequency of adverse events. No relevant changes in any laboratory parameter.
CONCLUSIONS:
The results have proven confirmatively the equivalent effect of Phlogenzym^® and the NSAID diclofenac. Because of the better benefit/risk-ratio, Phlogenzym is a real and good alternative to NSAIDs in the treatment of an activated gonarthritis.