Synopsis
Name of the sponsor
Takeda Pharmaceutical company Limited
Name of the finished product
Dasen® tablet (10 mg tablet)
Name of active ingredient
Serrapeptase
Title of the study
Post-marketing clinical study on serrapeptase (Dasen® tablet) in
patients with sprained ankle
Study centers:
40 study centers
Related publications
None
Study period
(Date of obtaining first subject’s
informed consent - Date of completing
the study treatment in the last subject)
First subject enrolled: January 4, 2008
Phase of development:
Phase IV
Objective of the study
To investigate the efficacy of serrapeptase (Dasen® tablet) at a daily
Last subject completed: May 27, 2009
dosage of 30 mg by a double-blind, placebo controlled, parallel group,
comparative study using “injured ankle joint sectional area” measured
by multislice CT as the primary endpoint in patients with sprained
ankle joints.
Method of the study
Multicenter, double-blind, placebo controlled, parallel group
comparative
Number of subjects
<At planning>
(planned and analyzed)
Number of registered subjects: 140 subjects per group, total of 280
subjects.
Number of subjects evaluable for the primary endpoint: 126 subjects
per group, total of 252 subjects.
<At analysis>
Efficacy analysis subjects: serrapeptase group 143 subjects, Placebo
group 136 subjects.
Safety analysis subjects: serrapeptase group 143 subjects, Placebo
group 136 subjects.
Main entrance criteria
<Subject population>
Patients aged at least 15 years with moderate (Grade II) or higher
severity of sprained ankle with clear swelling of the affected area, and
can undergo CT scan between 24-60 hr after the injury.
<Inclusion criteria >
1) Patients with moderate (Grade II) or higher severity of sprained ankle
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with clear swelling of the affected area at consultation (Visit 1)
2) Patients who can undergo CT scan between 24-60 hr after injury
3) Patients who are capable of submitting written consent prior to the
participation in the study.
< Exclusion criteria>
1) Patients with a history of surgery or scheduled surgery on the
injured ankle joint
2) Patients with an ankle joint complication such as arthritis
(rheumatism, gout, etc.), neuropathic arthritis (Charcot's joint
disease), diabetic foot disorder, and varicose vein
3) Patients with a history of hypersensitivity to the ingredient of
serrapeptase (Dasen® tablet)
Test product, dose and mode of
<Test product>
administration, and batch number
Serrapeptase (Dasen® tablet) 10 mg tablet
<Dose and mode of administration>
3 times daily orally after meals
<Batch number>
Z9162054, Z9162061
Comparator product, dose and mode
<Comparator product>
of administration, and batch number
Placebo tablet (containing no active ingredient)
<Dose and mode of administration>
3 times daily orally after meals
<Batch number>
Z9161062, Z9161081
Duration of Treatment
1 week
Endpoint
<Primary endpoint>
Injured ankle joint sectional area measured by multislice CT
<Secondary endpoint>
1) Injured ankle joint soft tissue area measured by multislice CT
2) Malleolar distance measured with a slide caliper technique
<Safety endpoints>
Adverse events, clinical laboratory test results.
Statistical Methods
<Efficacy analysis>
(1) Primary analysis
Using the “Full analysis set (FAS)”, for the changes in injured ankle
joint sectional area at Week 1 (Visit 2) from the start of treatment
(Visit 1), the summary statistics (number of subjects, mean, standard
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deviation, maximum, minimum, quartile value; the same in the
followings) and two-sided 95% confidence interval of the mean values
were estimated for each group to apply a one-sample t-test.
Additionally, based on an analysis of covariance model with the
covariate of injured ankle joint sectional area at the start of treatment
(Visit 1) and the independent variable of treatment group, an intergroup comparison were performed, and the adjusted mean value (LS
means), standard error, and two-sided 95% confidence interval were
calculated for each group. Furthermore, the adjusted mean difference
(LS means) between the serrapeptase group and Placebo group,
standard error, and two-sided 95% confidence interval were estimated.
(2) Secondary analysis
1) Injured ankle joint soft tissue area
2) Malleolar distance measured with a slide caliper technique
The same analysis as 1) Primary analysis of the primary endpoint was
performed on the changes in injured ankle soft tissue area and
malleolar distance measured with a slide caliper technique at Week 1
(Visit 2) from the start of treatment (Visit 1).
<Safety analyses>
Using “Safety data analysis set”, the following analyses were
performed:
(1) Treatment emergent adverse events (TEAE)
The incidence rates will be summarized by System Organ Class (SOC)
and Preferred Term (PT) for each treatment group.
(2) Clinical laboratory test results
The summary statistics of the results at the start of treatment (Visit 1),
results at each evaluation time point, and changes from the start of
treatment (Visit 1) will be determined for each treatment group.
Summary of Results
In the injured ankle joint sectional area, which is the primary
endpoint, there was no statistically significant difference between
the treatment group and placebo group.
However, when only subjects judged by the Central Judgement
Committee as “Errors in the CT slice images are anatomically < 1
mm.” based on the CT imaging were analyzed, there was a notable
difference between the serrapeptase group and Placebo group in the
LS means compared to the results of overall subjects.
The results above suggested possibility to find superiority over the
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placebo group by improving uniformity of pre- and post-treatment
evaluation region.
With regard to safety, there was no difference between both groups
on incidence of adverse events, and there was no problem with
tolerance.
Date of Report
January 5, 2011
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