Phlogenzym® in the Treatment of
Chronic Prostatitis
Primary Investigators: Peter Schlüter, M.D. 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. Phlogenzym® in the
Treatment of Chronic Prostatitis. 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
Name of Sponsor/Company: MUCOS Pharma GmbH & Co. Malvenweg 2,
D-82538 Geretsried
Name of Finished Product: Phlogenzym®
Name of Active Ingredient(s): Trypsin, Bromelin, Rutosid
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
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).