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Clinical Studies

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Statistical Report


Protocol title A double blind placebo control study to evaluate the efficacy of BioStick (BS) phototherapeutic device in the treatment of Aphthous Stomatitis.
Name of medical device BioStick
Study number Protocol Number: BS-01


Version: 1.2
Version date: 26/06/2009


 

Study description


    Study design:
    Number of centers: 1
    Blinding: Double blind
    Randomization: Block randomization
    Name of medical device: BioStick (BS) ™
    Comparator: BioStick (BS) with low light


Aim of study (main hypothesis)

    This study compares the efficacy of Syrolight BioStick device with active light to control with low light density

Objectives:

The primary objectives of this study are to:

  • Compare time to healing between the active device and the placebo control

The secondary objectives of this study are to:

  • Compare the reduction in pain, ability to speak eat and drink between the active and placebo treatment.
  • Evaluate patients’ satisfactory of the products.

Randomization

    Block randomization

Study endpoints

Primary endpoint:

    Efficacy:

    Compare the time to cure in days

    Compare the response grade for each group.


Secondary endpoints:

    Safety:

    Evaluation of adverse events.

Sample size

    Forty (40) subjects partitioned into 2 groups.

    Twenty allocated randomly to receive active treatment and 20 allocated to receive control treatment.

    The primary end point of this study is time to cure (number of days to obtain total cure). The expected difference between the active and placebo groups is anticipated to be at least two days (with standard deviation of two).

    A total of 40 enrolled patients (20 in each group) will provide 80% power at a 5% significance level and 95% Confidence Interval of Difference taking into account a 15% drop out rate.

Analysis set

    The full analysis set including all enrolled subjects in the study (ITT) was the primary analysis set.

    Due to one subject that was lost to follow-up and one subject that used additional medications during treatment the modified ITT served as the primary analysis set.

Analysis method

    Data was analyzed using the SPSS software (version 17.00, SPSS Inc.).

Baseline characteristics are presented as descriptive statistics (frequency (%) or mean, standard deviation (SD), standard error (SE) minimum, median and maximum).

Comparison between treatment arms of time to cure, number of treatments and lesion size is based on independent t-test.

Comparison of grade at baseline level is based on Mann Whitney test.

Safety is assessed descriptively.

Significance level was defined as a=0.05.

Missing data

    No imputation for missing values was applied.

Executive summary

Forty subjects with Aphthous Stomatitis participated in double blind placebo control study to evaluate the efficacy of BioStick (BO) phototherapeutic device in the treatment of Aphthous Stomatitis.

Compliance: 90% of placebo group and 100% of treated group complied with the study.

Demographic characteristics:
No significant differences between groups.
All subjects are Caucasian, the majority male, age of 36.8 ±11.9.

Baseline characteristics:
Subjects suffer from 1 to 3 lesions. The average lesion size of the placebo group was significantly smaller than in the treated group 13.56± 9.3 vs. 21.80±12.88, meaning that the treated group started the study in inferior condition.

The majority of both groups suffer from sever pain, burning sensation, speech and eating difficulties.

Most of the lesions were located in the lower lip.

Efficacy:

All subjects archived complete cure, as noted as complete recovery in all measurements and size of lesion equal to 0.

There are significant differences in the days to total cure, the treat group had significantly shorter time to cure than the placebo group (3.95±2.82 compared to 5.89±2.95, p=0.046)

There are significant differences in the number of treatments used until total cure, the treat group had significantly less treatments than the placebo group (12.56±7.30 compared to 20.00±8.94, p=0.010).


Subjective evaluation of efficacy

In the treated group the majority (60% to 73.3%) stated good to total cure in all measurements (pain, burning sensations, eating & speech difficulties) compared to approximately 29% to 35% in the placebo group.

Continence of use

80% of subjects from treated group grade the device better to much better that comparative treatments while only 16.7% from placebo group grade the device as much better.

The majority of both groups would like to use the device again (above 80%)

86.7% of the subjects in the treated group would like to buy the device compared to only 60% of subjects in the placebo group.

Safety:

No adverse events were recorded.

Tables:

  • 14.1 General and baseline characteristics

    Table 14.1.1: Study dates




    Placebo Treat
    N 18 20
    Date first subject screened 05.7.2007 13.6.2007
    Date last subject - screened 31.5.2009 05.6.2009
    Date last subject – Final visit 03.6.2009 14.6.2009

    Table 14.1.3: Demographic characteristics




    Placebo Treat P value


    N % N %
    Gender Male 11 61.1% 11 55.0% 0.752*

    Female 7 38.9% 9 45.0%
    Race Caucasian 18 100.0% 20 100.0% 1.000*







    Age (years) N 18 20 0.713**

    Mean 36.0 37.5

    Median 30.0 38.0

    SD 12.8 11.3

    Minimum 21.0 20.0

    Maximum 61.0 56.0

    The majority in both groups are women, all from Caucasian origin.

    The average age was 36 for placebo group and 37.5 for treated group.

    No significant differences in the demographic characteristics.

  • Table 14.1.4: Aphthous stomatitis condition at baseline



    Placebo Treat P value

    N 18 20 0.601
    Time from
    diagnosis
    ( Days)
    Mean 1.39 1.20
    Median 1.00 1.00
    SD .61 .70
    Minimum .00 .00
    Maximum 2.00 2.00





    Suffered in the past N % 15 83.3% 19 95.0% 0.328
    Treated in the past N % 13 72.2% 14 70.0% 1.000

    Days from diagnosis: 50% of subject arrived to the clinic within 1 day.

    The majority suffered in the past (above 83%) and 70% of both groups were treated in the past.

    Table 14.1.4.1: Past Medication

    No past medication recoded

    Table 14.1.5: Enrollment status

    Table 14.1.5.1: Number of lesions:


    Number of lesions Placebo Treat P value
    N % N %
    One lesion 13 72.2% 14 70.0% 0.979
    Two lesions 4 22.2% 5 25.0%
    Three lesions 1 5.6% 1 5.0%

    The majority of subjects in both groups (70%) had one lesion.

     

    Table 14.1.5.2: Location of lesions:




    Lesion 1 Lesion2 Lesion 3

    Placebo Treat Placebo Treat Placebo Treat

    N % N % N % N % N % N %
    1 Gingival Mucosa 3 16.7 6 30.0 3 50.0 2 33.3



    2 Tongue 6 33.3 2 10.0 1 16.7 2 33.3



    3 Upper Lip 1 5.6 1 5.0 1 16.7 1 16.7



    4 Lower Lip 7 38.9 8 40.0 1 16.7 1 16.7

    1 100%
    5 Hard palate 1 5.6









    6 Soft palate

    3 15.0



    1 100%

    Total 18 100.0 20 100.0







    The majority of lesions are in the lower lip for both groups.

    Table 14.1.5.3: Size of lesions (mm2):





    Treatment


    Placebo Treat P value
    Lesion 1 Size (mm2) N 18 20 0.031
    Mean 13.56 21.80
    Median 12.00 16.00
    SD 9.30 12.88
    Minimum 2.00 9.00
    Maximum 30.00 48.00
    Lesion 2 Size (mm2) N 6 6 0.421
    Mean 7.50 11.17
    Median 6.00 9.00
    SD 4.72 9.60
    Minimum 2.00 2.00
    Maximum 16.00 28.00
    Lesion 3 Size (mm2) N 1 1
    Mean 9.00 6.00
    Median 9.00 6.00
    SD . .
    Minimum 9.00 6.00
    Maximum 9.00 6.00

    Lesion 1: at baseline there are significant differences in the first lesion size, the treatment group has significantly bigger lesions compared to the placebo 21.80 mm2 vs. 13.56 mm2 respectively (p=0.031)

    Lesion 2: same trend but not statistically significant.

    Table 14.1.5.4: Condition of lesion at baseline





    Placebo Treat P value
    N % N %
    Pain None 1 5.6% 0 .0% 0.806
    Moderate 5 27.8% 6 30.0%
    Severe 12 66.7% 14 70.0%
    Burning Sensation None 1 5.6% 1 5.0% 0.874
    Mild 2 11.1% 0 .0%
    Moderate 4 22.2% 7 35.0%
    Severe 11 61.1% 12 60.0%
    Speech Difficulties None 3 16.7% 2 10.0% 0.613
    Mild 1 5.6% 2 10.0%
    Moderate 5 27.8% 4 20.0%
    Severe 9 50.0% 12 60.0%
    Eating Drinking Difficulties None 1 5.6% 0 .0% 0.919
    Mild 0 .0% 1 5.0%
    Moderate 3 16.7% 4 20.0%
    Severe 14 77.8% 15 75.0%

    The majority of both groups suffer from sever pain, burning sensation, speech and eating difficulties.

    Table 14.1.6: Medical History




    Placebo Treat P value
    N % N %
    Number of subjects 3 16.67% 0 0%
    Description of findings





    Hypercholesterolemia + hypertension 1 5.6% 0 0%

    Hypothyroidism 1 5.6% 0 0%

    Penicillin allergy 1 5.6% 0 0%

    Three subjects from the placebo group had some non related medical history.

    Table 14.1.7: Medication History

    No Medications were stopped within the last 14 days.

     

    Table 14.1.8: Subject validity status for analysis


    Placebo Treat

    N % N %
    Number of subjects 20 100% 20 100%
    Complete study 18 90% 20 100%
    Reasons for incomplete



    Lost to Follow up 1 5.0%

    Protocol violation use of other medication 1 5.0%


    There were two subjects that didn’t complete the study, both from the Placebo group.

  • 14.2 Efficacy – Objective evaluation

    Table 14.2.1: Time to total cure



    Treatment *P value
    Placebo Treat
    Days To Total Cure N 18 20 0.046
    Mean 5.89 3.95
    Median 5.50 3.00
    SD 2.95 2.82
    Minimum 2.00 1.00
    Maximum 12.00 10.00
    Number of treatments during period N 18 18 0.010
    Mean 20.00 12.56
    Median 19.50 9.50
    SD 8.94 7.30
    Minimum 7.00 5.00
    Maximum 39.00 30.00
    Total days in treatment N 18 20 0.041
    Mean 6.89 4.90
    Median 6.50 4.00
    SD 2.95 2.83
    Minimum 3.00 2.00
    Maximum 13.00 11.00
    Rate of use (number of treatments/days) N 18 18 0.724
    Mean 2.87 2.84
    Median 3.00 3.00
    SD .23 .28
    Minimum 2.33 2.00
    Maximum 3.00 3.00

    *p value based on independent t-test

    There are significant differences in the days to total cure, the treat group had significantly shorter time to cure than the placebo group (3.95±2.82 compared to 5.89±2.95, p=0.046)

    There are significant differences in the number of treatments used until total cure, the treat group had significantly less treatments than the placebo group (12.56±7.30 compared to 20.00±8.94, p=0.010)
    There are no significant differences between groups in the rate of use (2.84±0.28 compared to 2.87±0.23, p=0.724)

     

    Fig 1: Number of days to total cure

    Fig 2: Number of treatments until total cure
    Table 14.2.2: Improvement in lesion condition at the end of follow up


    Placebo Treat

    N % N %
    Number of subjects 20 100% 20 100%
    Complete study 18 90% 20 100%
    Complete recovery



    Pain 18 100% 20 100%
    Burning sensation 18 100% 20 100%
    Speech difficulty 18 100% 20 100%
    Eating/Drinking difficulty 18 100% 20 100%
    General status of lesions 18 100% 20 100%

    All subjects in both groups demonstrated complete recovery

    Table 14.2.3: Lesion size at end of follow-up



    Treatment


    Placebo Treat
    Lesion 1 Size (mm2) N 18 20
    Mean 0 0
    Median 0 0
    SD 0 0
    Minimum 0 0
    Maximum 0 0
    Lesion 2 Size (mm2) N 6 6
    Mean 0 0
    Median 0 0
    SD 0 0
    Minimum 0 0
    Maximum 0 0
    Lesion 3 Size (mm2) N 1 1
    Mean 0 0
    Median 0 0
    SD . .
    Minimum 0 0
    Maximum 0 0

    All subjects in both groups demonstrated no lesions at the end of follow-up, therefore size equal to 0.

  • 14.3 Efficacy – Subjective evaluation

    Table 14.3.1: Time to total cure by home diary



    Placebo Treat P value
    Days to Cure Diary N 14 14 0.046
    Mean 5.86 3.64
    Median 5.50 2.00
    SD 2.82 2.76
    Minimum 2.00 1.00
    Maximum 12.00 9.00

    Table 14.3.2: Stage of cure after two days of treatments



    Total Worse No change Mild Moderate Good Total cure Good to
    total cure
    Placebo Pain 17 2 11.8% 7 41.2% 1 5.9% 2 11.8% 3 17.6% 2 11.8% 5 29.4%
    Burning sensation 17 2 11.8% 5 29.4% 4 23.5% 1 5.9% 3 17.6% 2 11.8% 5 29.4%
    Speech difficulty 17 2 11.8% 4 23.5% 4 23.5% 1 5.9% 4 23.5% 2 11.8% 6 35.3%
    Eating/Drinking difficulty 17 2 11.8% 5 29.4% 3 17.6% 1 5.9% 4 23.5% 2 11.8% 6 35.3%
    Treat Pain 15 0 0.0% 1 6.7% 3 20.0% 2 13.3% 2 13.3% 7 46.7% 9 60.0%
    Burning sensation 15 1 6.7% 1 6.7% 3 20.0% 1 6.7% 2 13.3% 7 46.7% 9 60.0%
    Speech difficulty 15 1 6.7% 0 0.0% 2 13.3% 3 20.0% 2 13.3% 7 46.7% 9 60.0%
    Eating/Drinking difficulty 15 0 0.0% 1 6.7% 0 0.0% 3 20.0% 2 13.3% 9 60.0% 11 73.3%

    In the treated group the majority (60% to 73.3%) stated good to total cure in all measurements compared to approximately 29% to 35% in the placebo group.

    Fig2: Stage of cure after two days of treatments

  • 14.4 Convenience of use – Subjective evaluation

    Table 14.4.1: Previous treatments


    Placebo Treat Total P value

    N % N % N
    Number of subjects 17 100% 16 100% 33
    Used previous treatments 12 70.6% 10 62.5% 22 0.721
    Aphtagon 6 50.0% 2 20.0%

    Kanka 1 8.3% 5 50.0%

    Oracorte 3 25.0% 3 30.0%

    Other 4 33.3% 3 30.0%

    The majority of the placebo group used Aphtagon in the past,

    The majority of the treat group used Kanka in the past.

    Table 14.4.2: Comparing the device to previous treatments



    Placebo Treat Total P value

    N % N % N
    Number of subjects 14 100% 11 100% 24
    Used previous treatments 12 70.6% 10 62.5% 22 0.721
    Grade effectiveness of device




    0.314
    Less effective 2 16.7% 2 20.0%

    Similar 3 25.0% 0 .0%

    Better 5 41.7% 4 40.0%

    Much better 2 16.7% 4 40.0%

    80% of subjects from treated group grade the device better to much better that comparative treatments.

    Only 16.7% from placebo group grade the device as much better,

    Table 14.4.3: Comfort of use


    Placebo Treat

    N % N %
    Comfort for use 14 100.0% 13 100.0%
    Comments



    Comfortable 8
    8
    Complicated to clean after each use 1


    Comfortable but not effective 1
    1
    If it was smaller it wouldl be better 1


    Depends on location

    1
    Too long 1


    Not greasy or sandy fill in mouth 1


    All subjects stated that the device is comfort for use

    Table 14.4.4: Side Effects



    Placebo Treat

    N % N %
    No side effects 16 100.0% 16 100.0%

    No side effects were recorded

    Table 14.4.5: Prefer to use the device again on the occurrence of aphta



    Placebo Treat

    N % N %
    Use again 12 80.0% 13 86.7%

    The majority of both groups would like to use the device again (above 80%)

    Table 14.4.6: Will you buy the device if exist in the market


    Placebo Treat

    N % N %
    Buy the device 9 60.0% 13 86.7%

    86.7% of the subjects in the treated group would like to buy the device compared to only 60% of subjects in the placebo group.

  • 14.5 Safety

    Table 14.5.1: Concomitant medications


    Group ID Drug Name Units Daily Dose Route Start date Ongoing Indication Related AE
    Placebo 3 elthroxin mg 100 PO 01.1.2002 Yes hypothyroidism No
    Placebo 21 t.simvastatin mg 40 PO 01.4.2007 Yes hypercholesterolemia No
    Table14.5.2: Treatment-emergent adverse events

    No adverse events were recorded.

    Table 14.5.3: Reasons for study termination



    Placebo Treat

    N % N %
    Number of subjects N 20 100 20 100
    Study completed



    Yes 18 90 20 100
    No 2 10% 0 0
    Reasons for premature termination



      Lost to follow-up
    1 5 0 0
      Protocol violation (use additional medications)
    1 5 0 0
  • Clinical Studies

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    Statistical Report


    Protocol title A double blind placebo control study to evaluate the efficacy of BioStick (BS) phototherapeutic device in the treatment of Aphthous Stomatitis.
    Name of medical device BioStick
    Study number Protocol Number: BS-01


    Version: 1.2
    Version date: 26/06/2009


     

    Study description


      Study design:
      Number of centers: 1
      Blinding: Double blind
      Randomization: Block randomization
      Name of medical device: BioStick (BS) ™
      Comparator: BioStick (BS) with low light


    Aim of study (main hypothesis)

      This study compares the efficacy of Syrolight BioStick device with active light to control with low light density

    Objectives:

    The primary objectives of this study are to:

    • Compare time to healing between the active device and the placebo control

    The secondary objectives of this study are to:

    • Compare the reduction in pain, ability to speak eat and drink between the active and placebo treatment.
    • Evaluate patients’ satisfactory of the products.

    Randomization

      Block randomization

    Study endpoints

    Primary endpoint:

      Efficacy:

      Compare the time to cure in days

      Compare the response grade for each group.


    Secondary endpoints:

      Safety:

      Evaluation of adverse events.

    Sample size

      Forty (40) subjects partitioned into 2 groups.

      Twenty allocated randomly to receive active treatment and 20 allocated to receive control treatment.

      The primary end point of this study is time to cure (number of days to obtain total cure). The expected difference between the active and placebo groups is anticipated to be at least two days (with standard deviation of two).

      A total of 40 enrolled patients (20 in each group) will provide 80% power at a 5% significance level and 95% Confidence Interval of Difference taking into account a 15% drop out rate.

    Analysis set

      The full analysis set including all enrolled subjects in the study (ITT) was the primary analysis set.

      Due to one subject that was lost to follow-up and one subject that used additional medications during treatment the modified ITT served as the primary analysis set.

    Analysis method

      Data was analyzed using the SPSS software (version 17.00, SPSS Inc.).

    Baseline characteristics are presented as descriptive statistics (frequency (%) or mean, standard deviation (SD), standard error (SE) minimum, median and maximum).

    Comparison between treatment arms of time to cure, number of treatments and lesion size is based on independent t-test.

    Comparison of grade at baseline level is based on Mann Whitney test.

    Safety is assessed descriptively.

    Significance level was defined as a=0.05.

    Missing data

      No imputation for missing values was applied.

    Executive summary

    Forty subjects with Aphthous Stomatitis participated in double blind placebo control study to evaluate the efficacy of BioStick (BO) phototherapeutic device in the treatment of Aphthous Stomatitis.

    Compliance: 90% of placebo group and 100% of treated group complied with the study.

    Demographic characteristics:
    No significant differences between groups.
    All subjects are Caucasian, the majority male, age of 36.8 ±11.9.

    Baseline characteristics:
    Subjects suffer from 1 to 3 lesions. The average lesion size of the placebo group was significantly smaller than in the treated group 13.56± 9.3 vs. 21.80±12.88, meaning that the treated group started the study in inferior condition.

    The majority of both groups suffer from sever pain, burning sensation, speech and eating difficulties.

    Most of the lesions were located in the lower lip.

    Efficacy:

    All subjects archived complete cure, as noted as complete recovery in all measurements and size of lesion equal to 0.

    There are significant differences in the days to total cure, the treat group had significantly shorter time to cure than the placebo group (3.95±2.82 compared to 5.89±2.95, p=0.046)

    There are significant differences in the number of treatments used until total cure, the treat group had significantly less treatments than the placebo group (12.56±7.30 compared to 20.00±8.94, p=0.010).


    Subjective evaluation of efficacy

    In the treated group the majority (60% to 73.3%) stated good to total cure in all measurements (pain, burning sensations, eating & speech difficulties) compared to approximately 29% to 35% in the placebo group.

    Continence of use

    80% of subjects from treated group grade the device better to much better that comparative treatments while only 16.7% from placebo group grade the device as much better.

    The majority of both groups would like to use the device again (above 80%)

    86.7% of the subjects in the treated group would like to buy the device compared to only 60% of subjects in the placebo group.

    Safety:

    No adverse events were recorded.

    Tables:

  • 14.1 General and baseline characteristics

    Table 14.1.1: Study dates




    Placebo Treat
    N 18 20
    Date first subject screened 05.7.2007 13.6.2007
    Date last subject - screened 31.5.2009 05.6.2009
    Date last subject – Final visit 03.6.2009 14.6.2009

    Table 14.1.3: Demographic characteristics




    Placebo Treat P value


    N % N %
    Gender Male 11 61.1% 11 55.0% 0.752*

    Female 7 38.9% 9 45.0%
    Race Caucasian 18 100.0% 20 100.0% 1.000*







    Age (years) N 18 20 0.713**

    Mean 36.0 37.5

    Median 30.0 38.0

    SD 12.8 11.3

    Minimum 21.0 20.0

    Maximum 61.0 56.0

    The majority in both groups are women, all from Caucasian origin.

    The average age was 36 for placebo group and 37.5 for treated group.

    No significant differences in the demographic characteristics.

  • Table 14.1.4: Aphthous stomatitis condition at baseline



    Placebo Treat P value

    N 18 20 0.601
    Time from
    diagnosis
    ( Days)
    Mean 1.39 1.20
    Median 1.00 1.00
    SD .61 .70
    Minimum .00 .00
    Maximum 2.00 2.00





    Suffered in the past N % 15 83.3% 19 95.0% 0.328
    Treated in the past N % 13 72.2% 14 70.0% 1.000

    Days from diagnosis: 50% of subject arrived to the clinic within 1 day.

    The majority suffered in the past (above 83%) and 70% of both groups were treated in the past.

    Table 14.1.4.1: Past Medication

    No past medication recoded

    Table 14.1.5: Enrollment status

    Table 14.1.5.1: Number of lesions:


    Number of lesions Placebo Treat P value
    N % N %
    One lesion 13 72.2% 14 70.0% 0.979
    Two lesions 4 22.2% 5 25.0%
    Three lesions 1 5.6% 1 5.0%

    The majority of subjects in both groups (70%) had one lesion.

     

    Table 14.1.5.2: Location of lesions:




    Lesion 1 Lesion2 Lesion 3

    Placebo Treat Placebo Treat Placebo Treat

    N % N % N % N % N % N %
    1 Gingival Mucosa 3 16.7 6 30.0 3 50.0 2 33.3



    2 Tongue 6 33.3 2 10.0 1 16.7 2 33.3



    3 Upper Lip 1 5.6 1 5.0 1 16.7 1 16.7



    4 Lower Lip 7 38.9 8 40.0 1 16.7 1 16.7

    1 100%
    5 Hard palate 1 5.6









    6 Soft palate

    3 15.0



    1 100%

    Total 18 100.0 20 100.0







    The majority of lesions are in the lower lip for both groups.

    Table 14.1.5.3: Size of lesions (mm2):





    Treatment


    Placebo Treat P value
    Lesion 1 Size (mm2) N 18 20 0.031
    Mean 13.56 21.80
    Median 12.00 16.00
    SD 9.30 12.88
    Minimum 2.00 9.00
    Maximum 30.00 48.00
    Lesion 2 Size (mm2) N 6 6 0.421
    Mean 7.50 11.17
    Median 6.00 9.00
    SD 4.72 9.60
    Minimum 2.00 2.00
    Maximum 16.00 28.00
    Lesion 3 Size (mm2) N 1 1
    Mean 9.00 6.00
    Median 9.00 6.00
    SD . .
    Minimum 9.00 6.00
    Maximum 9.00 6.00

    Lesion 1: at baseline there are significant differences in the first lesion size, the treatment group has significantly bigger lesions compared to the placebo 21.80 mm2 vs. 13.56 mm2 respectively (p=0.031)

    Lesion 2: same trend but not statistically significant.

    Table 14.1.5.4: Condition of lesion at baseline





    Placebo Treat P value
    N % N %
    Pain None 1 5.6% 0 .0% 0.806
    Moderate 5 27.8% 6 30.0%
    Severe 12 66.7% 14 70.0%
    Burning Sensation None 1 5.6% 1 5.0% 0.874
    Mild 2 11.1% 0 .0%
    Moderate 4 22.2% 7 35.0%
    Severe 11 61.1% 12 60.0%
    Speech Difficulties None 3 16.7% 2 10.0% 0.613
    Mild 1 5.6% 2 10.0%
    Moderate 5 27.8% 4 20.0%
    Severe 9 50.0% 12 60.0%
    Eating Drinking Difficulties None 1 5.6% 0 .0% 0.919
    Mild 0 .0% 1 5.0%
    Moderate 3 16.7% 4 20.0%
    Severe 14 77.8% 15 75.0%

    The majority of both groups suffer from sever pain, burning sensation, speech and eating difficulties.

    Table 14.1.6: Medical History




    Placebo Treat P value
    N % N %
    Number of subjects 3 16.67% 0 0%
    Description of findings





    Hypercholesterolemia + hypertension 1 5.6% 0 0%

    Hypothyroidism 1 5.6% 0 0%

    Penicillin allergy 1 5.6% 0 0%

    Three subjects from the placebo group had some non related medical history.

    Table 14.1.7: Medication History

    No Medications were stopped within the last 14 days.

     

    Table 14.1.8: Subject validity status for analysis


    Placebo Treat

    N % N %
    Number of subjects 20 100% 20 100%
    Complete study 18 90% 20 100%
    Reasons for incomplete



    Lost to Follow up 1 5.0%

    Protocol violation use of other medication 1 5.0%


    There were two subjects that didn’t complete the study, both from the Placebo group.

  • 14.2 Efficacy – Objective evaluation

    Table 14.2.1: Time to total cure



    Treatment *P value
    Placebo Treat
    Days To Total Cure N 18 20 0.046
    Mean 5.89 3.95
    Median 5.50 3.00
    SD 2.95 2.82
    Minimum 2.00 1.00
    Maximum 12.00 10.00
    Number of treatments during period N 18 18 0.010
    Mean 20.00 12.56
    Median 19.50 9.50
    SD 8.94 7.30
    Minimum 7.00 5.00
    Maximum 39.00 30.00
    Total days in treatment N 18 20 0.041
    Mean 6.89 4.90
    Median 6.50 4.00
    SD 2.95 2.83
    Minimum 3.00 2.00
    Maximum 13.00 11.00
    Rate of use (number of treatments/days) N 18 18 0.724
    Mean 2.87 2.84
    Median 3.00 3.00
    SD .23 .28
    Minimum 2.33 2.00
    Maximum 3.00 3.00

    *p value based on independent t-test

    There are significant differences in the days to total cure, the treat group had significantly shorter time to cure than the placebo group (3.95±2.82 compared to 5.89±2.95, p=0.046)

    There are significant differences in the number of treatments used until total cure, the treat group had significantly less treatments than the placebo group (12.56±7.30 compared to 20.00±8.94, p=0.010)
    There are no significant differences between groups in the rate of use (2.84±0.28 compared to 2.87±0.23, p=0.724)

     

    Fig 1: Number of days to total cure

    Fig 2: Number of treatments until total cure
    Table 14.2.2: Improvement in lesion condition at the end of follow up


    Placebo Treat

    N % N %
    Number of subjects 20 100% 20 100%
    Complete study 18 90% 20 100%
    Complete recovery



    Pain 18 100% 20 100%
    Burning sensation 18 100% 20 100%
    Speech difficulty 18 100% 20 100%
    Eating/Drinking difficulty 18 100% 20 100%
    General status of lesions 18 100% 20 100%

    All subjects in both groups demonstrated complete recovery

    Table 14.2.3: Lesion size at end of follow-up



    Treatment


    Placebo Treat
    Lesion 1 Size (mm2) N 18 20
    Mean 0 0
    Median 0 0
    SD 0 0
    Minimum 0 0
    Maximum 0 0
    Lesion 2 Size (mm2) N 6 6
    Mean 0 0
    Median 0 0
    SD 0 0
    Minimum 0 0
    Maximum 0 0
    Lesion 3 Size (mm2) N 1 1
    Mean 0 0
    Median 0 0
    SD . .
    Minimum 0 0
    Maximum 0 0

    All subjects in both groups demonstrated no lesions at the end of follow-up, therefore size equal to 0.

  • 14.3 Efficacy – Subjective evaluation

    Table 14.3.1: Time to total cure by home diary



    Placebo Treat P value
    Days to Cure Diary N 14 14 0.046
    Mean 5.86 3.64
    Median 5.50 2.00
    SD 2.82 2.76
    Minimum 2.00 1.00
    Maximum 12.00 9.00

    Table 14.3.2: Stage of cure after two days of treatments



    Total Worse No change Mild Moderate Good Total cure Good to
    total cure
    Placebo Pain 17 2 11.8% 7 41.2% 1 5.9% 2 11.8% 3 17.6% 2 11.8% 5 29.4%
    Burning sensation 17 2 11.8% 5 29.4% 4 23.5% 1 5.9% 3 17.6% 2 11.8% 5 29.4%
    Speech difficulty 17 2 11.8% 4 23.5% 4 23.5% 1 5.9% 4 23.5% 2 11.8% 6 35.3%
    Eating/Drinking difficulty 17 2 11.8% 5 29.4% 3 17.6% 1 5.9% 4 23.5% 2 11.8% 6 35.3%
    Treat Pain 15 0 0.0% 1 6.7% 3 20.0% 2 13.3% 2 13.3% 7 46.7% 9 60.0%
    Burning sensation 15 1 6.7% 1 6.7% 3 20.0% 1 6.7% 2 13.3% 7 46.7% 9 60.0%
    Speech difficulty 15 1 6.7% 0 0.0% 2 13.3% 3 20.0% 2 13.3% 7 46.7% 9 60.0%
    Eating/Drinking difficulty 15 0 0.0% 1 6.7% 0 0.0% 3 20.0% 2 13.3% 9 60.0% 11 73.3%

    In the treated group the majority (60% to 73.3%) stated good to total cure in all measurements compared to approximately 29% to 35% in the placebo group.

    Fig2: Stage of cure after two days of treatments

  • 14.4 Convenience of use – Subjective evaluation

    Table 14.4.1: Previous treatments


    Placebo Treat Total P value

    N % N % N
    Number of subjects 17 100% 16 100% 33
    Used previous treatments 12 70.6% 10 62.5% 22 0.721
    Aphtagon 6 50.0% 2 20.0%

    Kanka 1 8.3% 5 50.0%

    Oracorte 3 25.0% 3 30.0%

    Other 4 33.3% 3 30.0%

    The majority of the placebo group used Aphtagon in the past,

    The majority of the treat group used Kanka in the past.

    Table 14.4.2: Comparing the device to previous treatments



    Placebo Treat Total P value

    N % N % N
    Number of subjects 14 100% 11 100% 24
    Used previous treatments 12 70.6% 10 62.5% 22 0.721
    Grade effectiveness of device




    0.314
    Less effective 2 16.7% 2 20.0%

    Similar 3 25.0% 0 .0%

    Better 5 41.7% 4 40.0%

    Much better 2 16.7% 4 40.0%

    80% of subjects from treated group grade the device better to much better that comparative treatments.

    Only 16.7% from placebo group grade the device as much better,

    Table 14.4.3: Comfort of use


    Placebo Treat

    N % N %
    Comfort for use 14 100.0% 13 100.0%
    Comments



    Comfortable 8
    8
    Complicated to clean after each use 1


    Comfortable but not effective 1
    1
    If it was smaller it wouldl be better 1


    Depends on location

    1
    Too long 1


    Not greasy or sandy fill in mouth 1


    All subjects stated that the device is comfort for use

    Table 14.4.4: Side Effects



    Placebo Treat

    N % N %
    No side effects 16 100.0% 16 100.0%

    No side effects were recorded

    Table 14.4.5: Prefer to use the device again on the occurrence of aphta



    Placebo Treat

    N % N %
    Use again 12 80.0% 13 86.7%

    The majority of both groups would like to use the device again (above 80%)

    Table 14.4.6: Will you buy the device if exist in the market


    Placebo Treat

    N % N %
    Buy the device 9 60.0% 13 86.7%

    86.7% of the subjects in the treated group would like to buy the device compared to only 60% of subjects in the placebo group.

  • 14.5 Safety

    Table 14.5.1: Concomitant medications


    Group ID Drug Name Units Daily Dose Route Start date Ongoing Indication Related AE
    Placebo 3 elthroxin mg 100 PO 01.1.2002 Yes hypothyroidism No
    Placebo 21 t.simvastatin mg 40 PO 01.4.2007 Yes hypercholesterolemia No
    Table14.5.2: Treatment-emergent adverse events

    No adverse events were recorded.

    Table 14.5.3: Reasons for study termination



    Placebo Treat

    N % N %
    Number of subjects N 20 100 20 100
    Study completed



    Yes 18 90 20 100
    No 2 10% 0 0
    Reasons for premature termination



      Lost to follow-up
    1 5 0 0
      Protocol violation (use additional medications)
    1 5 0 0
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