Acne Vulgaris
Conditions
Brief summary
To assess the efficacy and safety of different concentrations of CD5789 cream in participants with acne vulgaris for the purpose of dose identification.
Interventions
DRUGCD5789 25 µg/g cream
CD5789 25 µg/g cream applied once daily
DRUGCD5789 50 µg/g cream
CD5789 50 µg/g cream applied once daily
DRUGCD5789 100 µg/g cream
CD5789 100 µg/g cream applied once daily
DRUGTazarotene 0.1% gel
Tazarotene 0.1% gel applied once daily
DRUGVehicle cream
Vehicle cream applied once daily
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participant, 12 to 35 years old with the following characteristics: * Facial acne severity grade of the following: * Stratum 1: IGA score of 3 or 4 * Stratum 2: IGA score of 4 * Stratum 3: IGA score of 3 or 4 * A minimum of 30 non-inflammatory lesions and fulfills the criteria of one of the following strata: * Stratum 1: A minimum of 20 but not more than 40 inflammatory lesions, and a maximum of one nodule on the face. * Stratum 2: More than 40 inflammatory lesions, and up to four nodules on the face. * Stratum 3: Participants of Japanese origin with at least 20 inflammatory lesions and up to four nodules on the face. * Note: Participants of Japanese origin will not be included in Stratum 1 or Stratum 2. Japanese origin is defined as all four grandparents were born in Japan.
Exclusion criteria
* The presence of severe forms of acne (acne conglobata, acne fulminans) or secondary acne form (chloracne, drug-induced acne, etc.) * Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with the interpretation of the clinical trial results and/or put the participant at significant risk (according to the Investigator's judgment) if the participant participates in the clinical trial. * Known or suspected allergies or sensitivities to any components of any of the study drugs. * Current participation in any other clinical trial of a drug or device OR past participation within the 30 days prior to the Baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Success Rate 1 (SR1) | From Baseline at Week 12 | Success Rate 1 was defined as percentage of participants who achieved at least a two-point reduction in the Investigator Global Assessment (IGA) scale from baseline at week 12. Evaluation of acne was performed by the investigator based on the following 5 point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, higher score indicated higher severity. All missing values were imputed by last observation carried forward (LOCF). |
| Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | Baseline, Week 12 | The lesion counts were performed by the Investigator. Total lesion counts was the sum of inflammatory, non-inflammatory lesions and nodules. All missing values were imputed by LOCF. |
| Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | Baseline, Week 12 | The lesion counts were performed by the Investigator. Total lesion counts was the sum of inflammatory, non-inflammatory lesions and nodules. All missing values were imputed by LOCF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Success Rate 2 (SR2) | From Baseline to Week 12 | Success Rate 2 (SR2) was defined as the percentage of participants rated Clear (Grade 0) or Almost clear (Grade 1) with at least a two-point reduction on the IGA scale from Baseline to Week 12. Evaluation of acne was performed by the investigator based on the following 5 point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, higher score indicated higher severity. All missing values were imputed by LOCF. |
| Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Baseline, Week 12 | The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 1 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). All missing values were imputed by LOCF. |
| Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Baseline, Week 12 | The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 1 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). All missing values were imputed by LOCF. Percent changes in lesion counts equals (Week 12 count minus Baseline count) divided by Baseline count multiplied by 100. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in United States. A total of 422 participants were screened between 20 June 2012 to 01 May 2013. Of which, 118 were screen failures. Screen failures were mainly due to inclusion criteria not met. A total of 304 participants were randomized in the study.
Pre-assignment details
Participants randomized were stratified according to ethnic origin, acne severity & number of lesions as: Stratum 1: Non-Japanese, Investigator's Global Assessment (IGA) of 3/4, \>= 20 but \<= 40 inflammatory and \>=30 non-inflammatory lesions and \<=1 nodule on face; Stratum 2: Non-Japanese, IGA of 4, \>40 inflammatory & \>= 30 non-inflammatory lesions and \<=4 nodules on face; Stratum 3: Japanese origin, IGA of 3 or 4, \>= 20 inflammatory & \>= 30 non-inflammatory lesions & \<= 4 nodules on face.
Participants by arm
| Arm | Count |
|---|---|
| CD5789 25 mcg/g Cream Participants randomized in stratum 1, 2 and 3 were applied with 25 microgram per gram (mcg/g) CD5789 cream, once daily for 12 weeks. | 61 |
| CD5789 50 mcg/g Cream Participants randomized in stratum 1, 2 and 3 were applied with 50 microgram per gram (mcg/g) CD5789 50 once daily for 12 weeks. | 61 |
| CD5789 100 mcg/g Cream Participants randomized in stratum 1, 2 and 3 were applied with 100 microgram per gram (mcg/g) CD5789 cream, once daily for 12 weeks. | 60 |
| Tazarotene 0.1% Gel Participants randomized in stratum 1 and 2 were applied with Tazarotene 0.1% Gel, once daily for 12 weeks. | 61 |
| Vehicle Cream Participants randomized in stratum 1, 2 and 3 were applied with Vehicle Cream once daily for 12 weeks. | 61 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 3 | 2 | 1 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 5 | 2 | 4 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 3 | 1 | 5 |
Baseline characteristics
| Characteristic | CD5789 25 mcg/g Cream | Total | Vehicle Cream | Tazarotene 0.1% Gel | CD5789 100 mcg/g Cream | CD5789 50 mcg/g Cream |
|---|---|---|---|---|---|---|
| Age, Continuous | 18.1 years STANDARD_DEVIATION 5.26 | 18.2 years STANDARD_DEVIATION 5.03 | 18.3 years STANDARD_DEVIATION 4.84 | 18.3 years STANDARD_DEVIATION 4.83 | 18.3 years STANDARD_DEVIATION 5.59 | 18.2 years STANDARD_DEVIATION 4.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 49 Participants | 13 Participants | 12 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 52 Participants | 249 Participants | 47 Participants | 47 Participants | 52 Participants | 51 Participants |
| Sex: Female, Male Female | 15 Participants | 65 Participants | 13 Participants | 17 Participants | 12 Participants | 8 Participants |
| Sex: Female, Male Male | 46 Participants | 239 Participants | 48 Participants | 44 Participants | 48 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 61 | 0 / 60 | 0 / 61 | 0 / 61 |
| other Total, other adverse events | 15 / 61 | 17 / 61 | 23 / 60 | 24 / 61 | 18 / 61 |
| serious Total, serious adverse events | 1 / 61 | 1 / 61 | 0 / 60 | 0 / 61 | 1 / 61 |
Outcome results
Primary
Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF)
The lesion counts were performed by the Investigator. Total lesion counts was the sum of inflammatory, non-inflammatory lesions and nodules. All missing values were imputed by LOCF.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CD5789 25 mcg/g Cream | Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -53.61 lesion count | Standard Error 8.314 |
| CD5789 50 mcg/g Cream | Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -54.75 lesion count | Standard Error 8.261 |
| CD5789 100 mcg/g Cream | Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -54.99 lesion count | Standard Error 8.296 |
| Tazarotene 0.1% Gel | Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -59.84 lesion count | Standard Error 8.301 |
| CD5789 Vehicle Cream | Absolute Change From Baseline in Total Lesion Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -46.87 lesion count | Standard Error 7.934 |
Comparison: Analysis was performed using analysis of covariance (ANCOVA) with terms for treatment, stratum, and Baseline lesion count as covariate.p-value: 0.10895% CI: [-14.96, 1.48]ANCOVA
Comparison: Analysis was performed using analysis of covariance (ANCOVA) with terms for treatment, stratum, and Baseline lesion count as covariate.p-value: 0.0695% CI: [-16.11, 0.34]ANCOVA
Comparison: Analysis was performed using ANCOVA with terms for treatment, stratum, treatment stratum, and with Baseline lesion count as covariate.p-value: 0.05495% CI: [-16.35, 0.13]ANCOVA
Comparison: Analysis was performed using ANCOVA with terms for treatment, stratum, treatment stratum, and with Baseline lesion count as covariate.p-value: 0.00295% CI: [-21.18, -4.76]ANCOVA
Primary
Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF)
The lesion counts were performed by the Investigator. Total lesion counts was the sum of inflammatory, non-inflammatory lesions and nodules. All missing values were imputed by LOCF.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CD5789 25 mcg/g Cream | Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -47.59 percentage change | Standard Deviation 28.474 |
| CD5789 50 mcg/g Cream | Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -49.87 percentage change | Standard Deviation 24.731 |
| CD5789 100 mcg/g Cream | Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -50.72 percentage change | Standard Deviation 24.885 |
| Tazarotene 0.1% Gel | Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -55.07 percentage change | Standard Deviation 26.295 |
| CD5789 Vehicle Cream | Percentage Change From Baseline in Total Lesion Counts at Week 12 Using Last Observation Carried Forward (LOCF) | -40.48 percentage change | Standard Deviation 28.968 |
p-value: 0.067Cochran-Mantel-Haenszel
p-value: 0.054Cochran-Mantel-Haenszel
p-value: 0.038Cochran-Mantel-Haenszel
p-value: 0.003Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Success Rate 1 (SR1)
Success Rate 1 was defined as percentage of participants who achieved at least a two-point reduction in the Investigator Global Assessment (IGA) scale from baseline at week 12. Evaluation of acne was performed by the investigator based on the following 5 point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, higher score indicated higher severity. All missing values were imputed by last observation carried forward (LOCF).
Time frame: From Baseline at Week 12
Population: Analysis was performed on Intent to treat (ITT) population that included all subjects who were randomized and to whom study drug was dispensed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD5789 25 mcg/g Cream | Percentage of Participants With Success Rate 1 (SR1) | 29.51 percentage of participants |
| CD5789 50 mcg/g Cream | Percentage of Participants With Success Rate 1 (SR1) | 32.79 percentage of participants |
| CD5789 100 mcg/g Cream | Percentage of Participants With Success Rate 1 (SR1) | 26.67 percentage of participants |
| Tazarotene 0.1% Gel | Percentage of Participants With Success Rate 1 (SR1) | 32.79 percentage of participants |
| CD5789 Vehicle Cream | Percentage of Participants With Success Rate 1 (SR1) | 16.39 percentage of participants |
Comparison: The 95% confidence interval on the difference between Vehicle and the specified treatment group success rates was based on normal approximation with continuity correction.p-value: 0.09695% CI: [-3.266, 29.495]Cochran-Mantel-Haenszel
Comparison: The 95% confidence interval on the difference between Vehicle and the specified treatment group success rates was based on normal approximation with continuity correctionp-value: 0.0495% CI: [-0.249, 33.036]Cochran-Mantel-Haenszel
Comparison: The 95% confidence interval on the difference between Vehicle and the specified treatment group success rates was based on normal approximation with continuity correction.p-value: 0.18495% CI: [-5.923, 26.47]Cochran-Mantel-Haenszel
Comparison: The 95% confidence interval on the difference between Vehicle and the specified treatment group success rates was based on normal approximation with continuity correction.p-value: 0.04195% CI: [-0.249, 33.036]Cochran-Mantel-Haenszel
Secondary
Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF)
The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 1 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). All missing values were imputed by LOCF.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD5789 25 mcg/g Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory Lesions | -19.67 lesion count | Standard Deviation 14.874 |
| CD5789 25 mcg/g Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory Lesions | -24.30 lesion count | Standard Deviation 21.633 |
| CD5789 50 mcg/g Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory Lesions | -21.11 lesion count | Standard Deviation 13.268 |
| CD5789 50 mcg/g Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory Lesions | -18.69 lesion count | Standard Deviation 12.895 |
| CD5789 100 mcg/g Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory Lesions | -19.32 lesion count | Standard Deviation 11.566 |
| CD5789 100 mcg/g Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory Lesions | -23.70 lesion count | Standard Deviation 18.39 |
| Tazarotene 0.1% Gel | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory Lesions | -28.26 lesion count | Standard Deviation 26.346 |
| Tazarotene 0.1% Gel | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory Lesions | -21.03 lesion count | Standard Deviation 13.89 |
| CD5789 Vehicle Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory Lesions | -17.74 lesion count | Standard Deviation 15.073 |
| CD5789 Vehicle Cream | Absolute Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory Lesions | -17.70 lesion count | Standard Deviation 17.745 |
Secondary
Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF)
The Inflammatory lesion count was the count of papules and pustules: papule was a small, solid elevation less than 1 cm in diameter, pustule was a small, circumscribed elevation of the skin that contains yellow-white exudate. The non-inflammatory lesion count was the count of open and closed comedones: Open comedone was a pigmented dilated pilosebaceous orifice (blackhead). Closed comedone was a tiny white papule (whitehead). All missing values were imputed by LOCF. Percent changes in lesion counts equals (Week 12 count minus Baseline count) divided by Baseline count multiplied by 100.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD5789 25 mcg/g Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory lesion count | -49.16 percentage change | Standard Deviation 35.711 |
| CD5789 25 mcg/g Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory lesion count | -46.34 percentage change | Standard Deviation 30.888 |
| CD5789 50 mcg/g Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory lesion count | -53.14 percentage change | Standard Deviation 30.187 |
| CD5789 50 mcg/g Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory lesion count | -45.26 percentage change | Standard Deviation 29.331 |
| CD5789 100 mcg/g Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory lesion count | -51.93 percentage change | Standard Deviation 27.255 |
| CD5789 100 mcg/g Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory lesion count | -49.57 percentage change | Standard Deviation 29.786 |
| Tazarotene 0.1% Gel | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory lesion count | -55.88 percentage change | Standard Deviation 28.913 |
| Tazarotene 0.1% Gel | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory lesion count | -53.09 percentage change | Standard Deviation 29.484 |
| CD5789 Vehicle Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Inflammatory lesion count | -41.70 percentage change | Standard Deviation 35.898 |
| CD5789 Vehicle Cream | Percentage Change From Baseline in Inflammatory and Non-inflammatory Lesion Count up to Week 12 Using Last Observation Carried Forward (LOCF) | Non-inflammatory lesion count | -38.20 percentage change | Standard Deviation 30.368 |
Secondary
Percentage of Participants With Success Rate 2 (SR2)
Success Rate 2 (SR2) was defined as the percentage of participants rated Clear (Grade 0) or Almost clear (Grade 1) with at least a two-point reduction on the IGA scale from Baseline to Week 12. Evaluation of acne was performed by the investigator based on the following 5 point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, higher score indicated higher severity. All missing values were imputed by LOCF.
Time frame: From Baseline to Week 12
Population: Analysis was performed on ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD5789 25 mcg/g Cream | Percentage of Participants With Success Rate 2 (SR2) | 13.11 percentage of participants |
| CD5789 50 mcg/g Cream | Percentage of Participants With Success Rate 2 (SR2) | 14.75 percentage of participants |
| CD5789 100 mcg/g Cream | Percentage of Participants With Success Rate 2 (SR2) | 16.67 percentage of participants |
| Tazarotene 0.1% Gel | Percentage of Participants With Success Rate 2 (SR2) | 21.31 percentage of participants |
| CD5789 Vehicle Cream | Percentage of Participants With Success Rate 2 (SR2) | 8.20 percentage of participants |