Parkinson's Disease
Conditions
Keywords
Rotigotine patch, Neupro, Parkinson's Disease
Brief summary
The primary objective of the study is to compare the adhesiveness of 2 different patch formulations of Rotigotine using the largest patch size of 40 cm\^2, under the assumption that both patch formulations show similar adhesiveness properties.
Interventions
DRUGRotigotine (Test product PR 2.3.1)
* Pharmaceutical form: Transdermal patch * Concentration: 8 mg/24 hours * Route of administration: Transdermal
DRUGRotigotine (Reference product PR 2.1.1)
* Pharmaceutical form: Transdermal patch * Concentration: 8 mg/24 hours * Route of administration: Transdermal
Sponsors
Pharmaceutical Health Sciences
Bracket Global
UCB BIOSCIENCES GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of idiopathic Parkinson's Disease * Subject has been on continuous treatment with commercially available Rotigotine transdermal patches (Neupro®) for at least 3 months prior to enrollment * Subject has been taking a stable Rotigotine dose including an 8 mg/24 hours (40 cm\^2) patch for at least 2 weeks prior to enrollment
Exclusion criteria
* Subject has any medical or psychiatric condition which, in the opinion of the investigator, could jeopardize or would compromise the subject's well-being or ability to participate in this study * Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or recently unsolved contact dermatitis * Subject has a history or present condition of an atopic or eczematous Dermatitis, Psoriasis, or an active skin disease * Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1) or Baseline (Visit 2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average Adhesiveness Score of 2 Days of 24 Hours Patch Application as Rated by the Investigator (or Designee) Assessed According to the EMA Draft Guideline | Patch adhesiveness was measured after 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). * 0 = \> 95 - 100 % of the patch area adheres * 1 = \> 90 - 95 % of the patch adheres * 2 = \> 85 - 90 % of the patch adheres * 3 = \> 80 - 85 % of the patch adheres * 4 = \> 75 - 80 % of the patch adheres * 5 = \> 70 - 75 % of the patch adheres * 6 = ≥ 50 - 70 % of the patch adheres * 7 = \< 50 % of the patch adheres * 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. The average of patches 1 and 2 is presented by Treatment Arm below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). * 0 = \>95 - 100 % of the patch area adheres * 1 = \>90 - 95 % of the patch adheres * 2 = \>85 - 90 % of the patch adheres * 3 = \>80 - 85 % of the patch adheres * 4 = \>75 - 80 % of the patch adheres * 5 = \>70 - 75 % of the patch adheres * 6 = ≥50 - 70 % of the patch adheres * 7 = \<50 % of the patch adheres * 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. |
| Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: * 0 (\>95-100% of patch adheres) \>\> 0 (FDA/CDER) * 1 (\>90-95% of patch adheres) \>\> 0 (FDA/CDER) * 2 (\>85-90% of patch adheres) \>\> 1 (FDA/CDER) * 3 (\>80-85% of patch adheres) \>\> 1 (FDA/CDER) * 4 ( \>75-80% of patch adheres) \>\> 1 (FDA/CDER) * 5 (\>70-75% of patch adheres) \>\> 2 (FDA/CDER) * 6 (≥50-70% of patch adheres) \>\> 2 (FDA/CDER) * 7 (\<50 % of patch adheres) \>\> 3 (FDA/CDER) * 8 (Patch completely detached) \>\> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies. |
| Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: * 0 (\>95-100% of patch adheres) \>\> 0 (FDA/CDER) * 1 (\>90-95% of patch adheres) \>\> 0 (FDA/CDER) * 2 (\>85-90% of patch adheres) \>\> 1 (FDA/CDER) * 3 (\>80-85% of patch adheres) \>\> 1 (FDA/CDER) * 4 ( \>75-80% of patch adheres) \>\> 1 (FDA/CDER) * 5 (\>70-75% of patch adheres) \>\> 2 (FDA/CDER) * 6 (≥50-70% of patch adheres) \>\> 2 (FDA/CDER) * 7 (\<50 % of patch adheres) \>\> 3 (FDA/CDER) * 8 (Patch completely detached) \>\> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies. |
| Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). * 0 = \>95 - 100 % of the patch area adheres * 1 = \>90 - 95 % of the patch adheres * 2 = \>85 - 90 % of the patch adheres * 3 = \>80 - 85 % of the patch adheres * 4 = \>75 - 80 % of the patch adheres * 5 = \>70 - 75 % of the patch adheres * 6 = ≥50 - 70 % of the patch adheres * 7 = \<50 % of the patch adheres * 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. |
| Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5 | The subject assessed the patch adhesiveness by using the following score: * 0 = Satisfied with adhesiveness * 1 = Moderately satisfied with adhesiveness * 2 = Moderately unsatisfied with adhesiveness * 3 = Unsatisfied with adhesiveness |
| Change in Average Patch Adhesiveness Score of 2 Days of 24 Hour Patch Application as Rated by the Investigator (or Designee), Assessed According to the FDA/Center for Drug Evaluation and Research (CDER) Score | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: * 0 (\>95-100% of patch adheres) \>\> 0 (FDA/CDER) * 1 (\>90-95% of patch adheres) \>\> 0 (FDA/CDER) * 2 (\>85-90% of patch adheres) \>\> 1 (FDA/CDER) * 3 (\>80-85% of patch adheres) \>\> 1 (FDA/CDER) * 4 ( \>75-80% of patch adheres) \>\> 1 (FDA/CDER) * 5 (\>70-75% of patch adheres) \>\> 2 (FDA/CDER) * 6 (≥50-70% of patch adheres) \>\> 2 (FDA/CDER) * 7 (\<50 % of patch adheres) \>\> 3 (FDA/CDER) * 8 (Patch completely detached) \>\> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies. |
| Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4 | The subject assessed the patch adhesiveness by using the following score: * 0 = Satisfied with adhesiveness * 1 = Moderately satisfied with adhesiveness * 2 = Moderately unsatisfied with adhesiveness * 3 = Unsatisfied with adhesiveness |
Countries
Germany
Participant flow
Recruitment details
This study started to enroll subjects in September 2014 in Germany and concluded in December 2014.
Pre-assignment details
Participant Flow refers to the Randomized Set.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm A-B 4 day treatment (Treatment A for 2 days (Day 1 and Day 2): Rotigotine transdermal patch 8 mg/24 hours, test product PR 2.3.1 followed by Treatment B for 2 days (Day 3 and Day 4): Rotigotine transdermal patch 8 mg/24 hours reference product PR 2.1.1) | 29 |
| Treatment Arm B-A 4 day treatment (Treatment B for 2 days (Day 1 and Day 2): Rotigotine transdermal patch 8 mg/24 hours reference product PR 2.1.1 followed by Treatment A for 2 days (Day 3 and Day 4): Rotigotine transdermal patch 8 mg/24 hours, test product PR 2.3.1) | 28 |
| Total Title | 57 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Safety follow up could not take place | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Arm A-B | Treatment Arm B-A | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 20 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 8 Participants | 19 Participants |
| Age, Continuous | 67.3 years STANDARD_DEVIATION 10.9 | 69.6 years STANDARD_DEVIATION 9.5 | 68.4 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 25 Participants | 19 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 57 | 1 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
Primary
Change in Average Adhesiveness Score of 2 Days of 24 Hours Patch Application as Rated by the Investigator (or Designee) Assessed According to the EMA Draft Guideline
The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). * 0 = \> 95 - 100 % of the patch area adheres * 1 = \> 90 - 95 % of the patch adheres * 2 = \> 85 - 90 % of the patch adheres * 3 = \> 80 - 85 % of the patch adheres * 4 = \> 75 - 80 % of the patch adheres * 5 = \> 70 - 75 % of the patch adheres * 6 = ≥ 50 - 70 % of the patch adheres * 7 = \< 50 % of the patch adheres * 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. The average of patches 1 and 2 is presented by Treatment Arm below.
Time frame: Patch adhesiveness was measured after 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change in Average Adhesiveness Score of 2 Days of 24 Hours Patch Application as Rated by the Investigator (or Designee) Assessed According to the EMA Draft Guideline | 1.04 units on a scale | Standard Deviation 1.33 |
| Treatment B | Change in Average Adhesiveness Score of 2 Days of 24 Hours Patch Application as Rated by the Investigator (or Designee) Assessed According to the EMA Draft Guideline | 2.15 units on a scale | Standard Deviation 1.96 |
Comparison: The change in average adhesiveness score was average score for Treatment B minus average score for Treatment A.
Secondary
Change in Average Patch Adhesiveness Score of 2 Days of 24 Hour Patch Application as Rated by the Investigator (or Designee), Assessed According to the FDA/Center for Drug Evaluation and Research (CDER) Score
The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: * 0 (\>95-100% of patch adheres) \>\> 0 (FDA/CDER) * 1 (\>90-95% of patch adheres) \>\> 0 (FDA/CDER) * 2 (\>85-90% of patch adheres) \>\> 1 (FDA/CDER) * 3 (\>80-85% of patch adheres) \>\> 1 (FDA/CDER) * 4 ( \>75-80% of patch adheres) \>\> 1 (FDA/CDER) * 5 (\>70-75% of patch adheres) \>\> 2 (FDA/CDER) * 6 (≥50-70% of patch adheres) \>\> 2 (FDA/CDER) * 7 (\<50 % of patch adheres) \>\> 3 (FDA/CDER) * 8 (Patch completely detached) \>\> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies.
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change in Average Patch Adhesiveness Score of 2 Days of 24 Hour Patch Application as Rated by the Investigator (or Designee), Assessed According to the FDA/Center for Drug Evaluation and Research (CDER) Score | 0.40 units on a scale | Standard Deviation 0.6 |
| Treatment B | Change in Average Patch Adhesiveness Score of 2 Days of 24 Hour Patch Application as Rated by the Investigator (or Designee), Assessed According to the FDA/Center for Drug Evaluation and Research (CDER) Score | 0.85 units on a scale | Standard Deviation 1.03 |
Comparison: The change in average adhesiveness score was average score for Treatment B minus average score for Treatment A.
Secondary
Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2
The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). * 0 = \>95 - 100 % of the patch area adheres * 1 = \>90 - 95 % of the patch adheres * 2 = \>85 - 90 % of the patch adheres * 3 = \>80 - 85 % of the patch adheres * 4 = \>75 - 80 % of the patch adheres * 5 = \>70 - 75 % of the patch adheres * 6 = ≥50 - 70 % of the patch adheres * 7 = \<50 % of the patch adheres * 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline.
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 95 % | 71.2 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 90 % - 95 % | 5.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 85 % - 90 % | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 80 % - 85 % | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 75 % - 80 % | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 70 % - 75 % | 1.9 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | <= 70 % | 9.6 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 95 % | 36.5 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 75 % - 80 % | 9.6 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 90 % - 95 % | 7.7 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | <= 70 % | 23.1 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 85 % - 90 % | 9.6 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 70 % - 75 % | 3.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | > 80 % - 85 % | 9.6 percentage of patches |
Secondary
Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1
The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: * 0 (\>95-100% of patch adheres) \>\> 0 (FDA/CDER) * 1 (\>90-95% of patch adheres) \>\> 0 (FDA/CDER) * 2 (\>85-90% of patch adheres) \>\> 1 (FDA/CDER) * 3 (\>80-85% of patch adheres) \>\> 1 (FDA/CDER) * 4 ( \>75-80% of patch adheres) \>\> 1 (FDA/CDER) * 5 (\>70-75% of patch adheres) \>\> 2 (FDA/CDER) * 6 (≥50-70% of patch adheres) \>\> 2 (FDA/CDER) * 7 (\<50 % of patch adheres) \>\> 3 (FDA/CDER) * 8 (Patch completely detached) \>\> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies.
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | >= 90 % | 76.9 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | 75 % -< 90 % | 15.4 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | 50 % -< 75 % | 1.9 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | < 50 % | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | Detached | 1.9 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | Detached | 7.7 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | >= 90 % | 63.5 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | < 50 % | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | 75 % -< 90 % | 17.3 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | 50 % -< 75 % | 11.5 percentage of patches |
Secondary
Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2
The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: * 0 (\>95-100% of patch adheres) \>\> 0 (FDA/CDER) * 1 (\>90-95% of patch adheres) \>\> 0 (FDA/CDER) * 2 (\>85-90% of patch adheres) \>\> 1 (FDA/CDER) * 3 (\>80-85% of patch adheres) \>\> 1 (FDA/CDER) * 4 ( \>75-80% of patch adheres) \>\> 1 (FDA/CDER) * 5 (\>70-75% of patch adheres) \>\> 2 (FDA/CDER) * 6 (≥50-70% of patch adheres) \>\> 2 (FDA/CDER) * 7 (\<50 % of patch adheres) \>\> 3 (FDA/CDER) * 8 (Patch completely detached) \>\> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies.
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | >= 90 % | 76.9 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | 75 % -< 90 % | 11.5 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | 50 % -< 75 % | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | < 50 % | 7.7 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | Detached | 0 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | Detached | 5.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | >= 90 % | 44.2 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | < 50 % | 3.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | 75 % -< 90 % | 28.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | 50 % -< 75 % | 17.3 percentage of patches |
Secondary
Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1
The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). * 0 = \>95 - 100 % of the patch area adheres * 1 = \>90 - 95 % of the patch adheres * 2 = \>85 - 90 % of the patch adheres * 3 = \>80 - 85 % of the patch adheres * 4 = \>75 - 80 % of the patch adheres * 5 = \>70 - 75 % of the patch adheres * 6 = ≥50 - 70 % of the patch adheres * 7 = \<50 % of the patch adheres * 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline.
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 95 % | 65.4 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 75 % - 80 % | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 85 % - 90 % | 7.7 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 70 % - 75 % | 0 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 90 % - 95 % | 11.5 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | <= 70 % | 7.7 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | Missing | 0 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 80 % - 85 % | 3.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | Missing | 0 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 95 % | 46.2 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 90 % - 95 % | 17.3 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 85 % - 90 % | 5.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 80 % - 85 % | 9.6 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 75 % - 80 % | 1.9 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | > 70 % - 75 % | 1.9 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | <= 70 % | 17.3 percentage of patches |
Secondary
Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1
The subject assessed the patch adhesiveness by using the following score: * 0 = Satisfied with adhesiveness * 1 = Moderately satisfied with adhesiveness * 2 = Moderately unsatisfied with adhesiveness * 3 = Unsatisfied with adhesiveness
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 0 = Satisfied with adhesiveness | 75.0 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 1 = Moderately satisfied with adhesiveness | 17.3 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 2 = Moderately unsatisfied with adhesiveness | 3.8 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 3 = Unsatisfied with adhesiveness | 3.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 3 = Unsatisfied with adhesiveness | 11.5 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 0 = Satisfied with adhesiveness | 65.4 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 2 = Moderately unsatisfied with adhesiveness | 9.6 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | 1 = Moderately satisfied with adhesiveness | 13.5 percentage of patches |
Secondary
Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2
The subject assessed the patch adhesiveness by using the following score: * 0 = Satisfied with adhesiveness * 1 = Moderately satisfied with adhesiveness * 2 = Moderately unsatisfied with adhesiveness * 3 = Unsatisfied with adhesiveness
Time frame: Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5
Population: Per Protocol Set (PPS), which was defined as all subjects who had at least 1 patch adhesiveness assessment after 24 hours of patch application by the investigator (or designee) for both treatments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 0 = Satisfied with adhesiveness | 73.1 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 1 = Moderately satisfied with adhesiveness | 15.4 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 2 = Moderately unsatisfied with adhesiveness | 9.6 percentage of patches |
| Treatment A | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 3 = Unsatisfied with adhesiveness | 1.9 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 3 = Unsatisfied with adhesiveness | 7.7 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 0 = Satisfied with adhesiveness | 59.6 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 2 = Moderately unsatisfied with adhesiveness | 5.8 percentage of patches |
| Treatment B | Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | 1 = Moderately satisfied with adhesiveness | 26.9 percentage of patches |