Phlogenzym® in the Treatment of Chronic Prostatitis

Efficacy and Tolerance
Study No.: MU-694422

Randomised double-blind study phase III with parallel groups vs. placebo according to the guidelines of good clinical practice (GCP)
Integrated final report according to ICH E3 guidelines

Primary Investigators: Peter Schlüter, M.D.

Gartenstrasse 16, D-69502 Hemsbach, Germany

Evaluation by: MUCOS Pharma GmbH & Co Clinical Research Dpt. Malvenweg 2, D-82538 Geretsried, Germany

Report by: PharmaScript, Primelweg 2, D-82538 Geretsried, Germany

Date of report: October 30th, 1997

Synopsis

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 chronic prostatitis.
Investigator(s):
Peter Schlüter, M.D., Gartenstrasse 16, D-69502 Hemsbach, Germany
Study centre(s):
Peter Schlüter, M.D., Gartenstrasse 16, D-69502 Hemsbach, Germany
Publication (reference/s):
Studied period (mo/years): 20 months
(date of first enrolment) Oct 27th, 1995 (pat. # 401)
(date of last completed) June 17th, 1997 (pat. # 480)		 Phase of development:
Phase III
Objectives:
To test efficacy and tolerance of Phlogenzymâ as compared with placebo.
Methodology:
Double-blind, randomised study with parallel groups.
Sum score calculated of different kinds of pain and symptoms (perineal pain, lumbar pain, inguinal pain, testicular pain, defecation pain, fever, miction, stranguria, dysuria, nycturia, burning when urinating) after two weeks of treatment. Stratum 1: patients with bacterial prostatitis; stratum 2: patients with abacterial prostatitis.
Number of patients (planned and analysed):
Planned 80; included 80; evaluated 80
Diagnosis and main criteria for inclusion:
Patients with bacterial or abacterial chronic prostatitis.
Test product, dose and mode of administration, batch number:
Phlogenzym: 90 mg bromelin, 48 mg trypsin, 100 mg rutosid x 3 H20,
2 tablets orally t.i.d. (= 6 tbl. per day), batch no.: 920 863
Duration of treatment:
4 weeks
Reference therapy, dose and mode of administration, batch number.
Placebo tablets, batch no.: 720 298, 2 tablets orally t.i.d. (= 6 tbl. per day)

 

 

Criteria for evaluation
Efficacy: Main endpoint: sum score after 2 weeks of treatment
Safety: Global judgement of tolerance (by physician and patients);
laboratory findings, adverse events
Statistical methods:
To test comparability of groups: Wilcoxon-Mann-Whitney (two-tailed);
to test difference of endpoints: Wilcoxon-Mann-Whitney with Mann-Whitney estimator (one-tailed) calculated with 95%Cl; diff. in number of adverse events: Fisher`s exact test (two-tailed).
SUMMARY - CONCLUSIONS

EFFICACY RESULTS:
Evaluating all patients the difference between the groups was statistically significant on the 0.01% level. The Mann-Whitney-statistics P(X<Y)+0.5P(X=Y) was 0.7987 and showed a big relevant difference for the enzyme preparation.
In patients which bacterial prostatitis the statistical significant difference was on the 1 % level in favor of the enzyme preparation. The Mann-Whitney-stastistics (0.7833) has proven big superiority.
In patients with abacterial prostatitis the difference was statistically significant on the 0.01 % level, the Mann-Whitney-stastistics (0.8333) showed big superiority of Phlogenzymâ .

SAFETY RESULTS:
The tolerance of the enzyme preparation was assumed better than placebo, in all judgements was a statistically signficant difference.
Nevertheless, in the enzyme group more adverse events occurred than in the placebo group (enzyme group: 25 a.e., placebo group: 15 a.e.). The difference was statistically significant in favor of the placebo group on the 5% level.
In laboratory findings no remarkable deteriorations were noticed.

CONCLUSIONS
The results of this study show that the enzyme preparation Phlogenzym® is an efficient and excellently tolerated drug in treatment of both bacterial and abacterial prostatitis.

Date of the report: October 30th, 1997

 

1. Summary

In this double-blind clinical study efficacy and tolerance of Phlogenzym® was tested in patients with chronic prostatitis. It was compared with placebo.

80 patients were planned, 40 patients received the enzyme preparation Phlogenzym® (enzyme group), and 40 patients placebo (placebo group). The recruited patients were subdivided into strata with bacterial prostatitis and abacterial prostatitis. In the enzyme group 17 patients had a bacterial and 23 an abacterial prostatitis and in the placebo group 19 patients were treated because of a bacterial and 21 because of an abacterial prostatitis. The data of all patients was evaluable.

The trial was carried out by Peter Schlüter, M.D., Gartenstrasse 16, D69502 Hemsbach, Germany.

Each patient received 2 tablets t.i.d. (i.e. 6 tablets per day) of the "enzyme tablets". In one group (enzyme group) the patients received Phlogenzym® and in the other group (placebo group) placebo tablets.

At baseline the patients were comparable with regard to age, height, weight (except the patients with abacterial prostatitis), manifestation of current prostatitis, last relapse, manifestation of the 1st prostatitis, and frequency of relapses in the previous year (except the patients with bacterial prostatitis): p > 0.05, Wilcoxon-Mann-Whitney-U-test.

As main endpoint for statistical evaluation a sum score calculated from perineal pain, lumbar pain, inguinal pain, testicular pain, defecation pain, fever, miction, strangury, dysuria, nycturia and burning when urinating after two weeks of therapy was defined.

As secondary criteria the various kinds of pain and symptoms, the consistency of the prostate, the state of the urine, the adverse events, and the global judgements by the physician and by the patients were evaluated descriptively.

The main endpoint showed statistically significant differences (p > 0.05) in the evaluation of all patients and of the strata with both bacterial prostatitis and abacterial prostatitis. The Mann-Whitney statistics allow the conclusion of superiority of the enzyme preparation, in all patients and in patients with abacterial prostatitis there was a big relevant difference (Mann-Whitney statistics: > 0.71 ), and in patients with bacterial prostatitis there was a medium relevant difference (Mann-Whitney statistics: > 0.64).

The secondary endpoints perineal pain, testicular pain, miction, strangury, and nycturia were significantly better in the enzyme group in all patients, and in both strata. Inguinal pain and dysuria were significantly better in the enzyme group in all patients and in abacterial prostatitis. Defecation pain was better in the enzyme group in all patients and in bacterial prostatitis. Inguinal pain was significantly better in the placebo group in bacterial prostatitis.

The urinalysis (tested by test strips: leukocytes, erythrocytes, protein, and sediment) improved in all patients.

In the tested laboratory parameters (creatinine, urea, Quick-value, gGT, AST, ALT, a1-antitrypsin, a2-macroglobulin, C-reactive protein, ceruloplasmin, a1-glycoprotein, haptoglobin, fibrinogen, total protein, albumin, a1-globulin, a2-globulin, b-globulin, g-globulin, IgG, IgA, IgM) only seven values deteriorated within a limit of ± 15%, all other values remained unchanged or improved.

The efficacy of the drug was judged in the enzyme group by the physician and by the patients as "very good" to "good". In the placebo group the physician and the patients judged the efficacy of the drug as "moderate" to "unsatisfactory". There were statistically significant differences between the groups (p < 0.0001 ).

The tolerance of the drugs was judged by the physician and by the patients in the enzyme group as "very good" to "good" and in the placebo group as "good". There were statistically significant differences between the groups (p < 0.05).

Adverse events were documented in 25 patients in the enzyme group (mainly gastro-intestinal complaints or inflammations), and in 15 patients in the placebo group (mainly inflammations), most of them not related to the test drug. They started on average after 16.8 days in the enzyme group and after 18.3 days in the placebo group. The duration was 6.4 days in the enzyme group and 7.5 days in the placebo group. They were judged as "moderate" in both groups. The patient's outcome was without damage. The difference between the groups was statistically significant in favor of the placebo group (p < 0.05).