Acne Vulgaris
Conditions
Brief summary
Demonstrate that a daily treatment regimen of adapalene 0.3%/benzoyl peroxide 2.5% gel + oral Doxycycline 200 mg is effective and safe in severe inflammatory acne with 3 or fewer nodules or cysts (non-nodulocystic) during a 12-week treatment period.
Detailed description
This Phase 4, 12-week, single-arm, open-label, multi-center investigational efficacy and safety study was conducted in subjects with severe inflammatory acne. Subjects who met the inclusion criteria and none of the exclusion criteria at the Screening visit returned to the clinic for baseline measures (Week 0) and to start treatment, which continued for up to 12 weeks. Treatment consisted of 2 investigational study drugs: * A/BPO 0.3%/2.5% gel applied to dry skin as directed by study staff once daily for 12 weeks, at night after washing. * Doxycycline hyclate 200 mg: each subject was to take 2 50-mg tablets of doxycycline hyclate in the morning and 2 at night, for a total of 4 tablets (a total of 200 mg) daily for 12 weeks.
Interventions
DRUGAdapalene 0.3% / benzoyl peroxide 2.5% emulsion gel
Topical acne therapy
DRUGOral doxycycline hyclate
Tetracycline-class oral antibacterial 200 mg daily (2 tablets \[50 mg\], twice daily)
Sponsors
Galderma R&D
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female subjects, 12 years of age or older at Screening visit. 2. Subjects with a clinical diagnosis of severe inflammatory acne (IGA score of 4). 3. Subjects with 4 or fewer nodules or cysts \> 1 cm in diameter on the face. 4. Subjects 18 years of age or older must read and sign the Informed Consent Form, which includes Photography Consent and HIPAA authorization, prior to any participation in the study. Consent will be obtained prior to any study-related procedures. Subjects under the age of 18 years must sign an Assent to Participate Form to participate in the study and must have one parent or guardian read and sign the Informed Consent Form prior to any study-related procedure. (The parent or guardian is not required to attend the following visits unless requested.) Key
Exclusion criteria
1. Subjects with nodulocystic or conglobate acne, acne fulminans, or secondary acne (chloracne, drug-induced acne, etc.). 2. Subjects with 5 or more acne nodules or cysts \> 1 cm in diameter on the face at Screening and Baseline visits. 3. Female subjects who are pregnant, nursing, or planning a pregnancy during the study. 4. Subjects who have used any systemic therapy directed at improving acne, including antibiotics, within 30 days prior to Baseline visit. 5. Subjects who are at risk in terms of precautions, warnings, and contraindications for the investigational study drugs (see Appendix 14.1 for package inserts for adapalene 0.3%/benzoyl peroxide 2.5% gel and doxycycline hyclate Tablets). 6. Subjects with any other condition or circumstance which, in the Investigator's opinion, may put the subject at risk (e.g., a history of significant renal disease with impairment of renal function), confound the study results, or interfere with the subject's participation in the study. 7. Sponsor and study site staff, relatives of staff members, or other individuals who would have access to the clinical study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Inflammatory Lesions | Week 12 | Change in Number of Inflammatory Lesions from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Lesion Count | Weeks 4, 8, and 12 | Percent Change From Baseline in Total Lesion Count. |
| Change From Baseline in Total Lesion Count | Weeks 4, 8, and 12 | Change From Baseline in Total Lesion Count. |
| Percent Change From Baseline in Inflammatory Lesion Count | Weeks 4, 8, and 12 | Percent Change From Baseline in Inflammatory Lesion Count. |
| Change From Baseline in Inflammatory Lesion Count | Weeks 4, 8, and 12 | Change From Baseline in Inflammatory Lesion Count. |
| Number and Percent of Subjects With IGA Success | Weeks 4, 8, and 12 | IGA Success is defined as an IGA rating of Clear (Grade 0) or Almost Clear (Grade 1) |
| Change From Baseline in Non-Inflammatory Lesion Count | Weeks 4, 8, and 12 | Change From Baseline in Non-Inflammatory Lesion Count. |
| Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates | Weeks 0, 4, 8, and 12 | At each visit, subjects were evaluated by the investigator to determine whether (in the opinion of the investigator) they would consider them as candidates for oral isotretinoin therapy. The outcome measure reports the number and % of subjects who, in the opinion of the investigator, were not considered to be a candidate for oral isotretinoin therapy. |
| Subject Assessment of Acne Improvement | Week 12 | Subject Assessment of Acne Improvement on a 6 point scale (0 = Complete Improvement, 1 = Marked Improvement, 2 = Moderate Improvement, 3 = Minimal Improvement, 4 = No Change, 5 = Worse). |
| Number and Percent of Adverse Events | Week 12 | Number and percent of subjects with any Treatment-Related Adverse Event |
| Percent Change From Baseline in Non-Inflammatory Lesion Count | Weeks 4, 8, and 12 | Percent Change From Baseline in Non-Inflammatory Lesion Count. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acne Treatment Topical adapalene 0.3% / benzoyl peroxide 2.5% emulsion gel (one application daily for 12 weeks)
Oral doxycycline hyclate, 200 mg per day (two 50-mg tablets twice daily for 12 weeks)
Adapalene 0.3% / benzoyl peroxide 2.5% emulsion gel: Topical acne therapy
Oral doxycycline hyclate: Tetracycline-class oral antibacterial 200 mg daily (2 tablets \[50 mg\], twice daily) | 175 |
| Total | 175 |
Baseline characteristics
| Characteristic | Acne Treatment |
|---|---|
| Age, Continuous | 19.6 years STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| IGA 4 (Investigator's Global Assessment Score) | 175 Participants |
| Inflammatory Lesion Count | 44.1 Lesion Count STANDARD_DEVIATION 21.29 |
| Non-inflammatory Lesion Count | 63.9 Lesion Count STANDARD_DEVIATION 38.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 139 Participants |
| Region of Enrollment United States | 175 participants |
| Sex: Female, Male Female | 97 Participants |
| Sex: Female, Male Male | 78 Participants |
| Total Lesion Count | 108.1 Lesion Count STANDARD_DEVIATION 48.43 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 175 |
| other Total, other adverse events | 22 / 175 |
| serious Total, serious adverse events | 0 / 175 |
Outcome results
Primary
Change in Number of Inflammatory Lesions
Change in Number of Inflammatory Lesions from baseline.
Time frame: Week 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acne Treatment | Change in Number of Inflammatory Lesions | -30.1 Inflammatory lesions | Standard Deviation 22.3 |
Secondary
Change From Baseline in Inflammatory Lesion Count
Change From Baseline in Inflammatory Lesion Count.
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acne Treatment | Change From Baseline in Inflammatory Lesion Count | Week 8 | -25.9 change in lesions | Standard Deviation 22.2 |
| Acne Treatment | Change From Baseline in Inflammatory Lesion Count | Week 12 | -30.1 change in lesions | Standard Deviation 22.3 |
| Acne Treatment | Change From Baseline in Inflammatory Lesion Count | Week 4 | -18.9 change in lesions | Standard Deviation 19.6 |
Secondary
Change From Baseline in Non-Inflammatory Lesion Count
Change From Baseline in Non-Inflammatory Lesion Count.
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acne Treatment | Change From Baseline in Non-Inflammatory Lesion Count | Week 4 | -24.9 change in lesions | Standard Deviation 28.4 |
| Acne Treatment | Change From Baseline in Non-Inflammatory Lesion Count | Week 8 | -33.6 change in lesions | Standard Deviation 33 |
| Acne Treatment | Change From Baseline in Non-Inflammatory Lesion Count | Week 12 | -39.1 change in lesions | Standard Deviation 36.2 |
Secondary
Change From Baseline in Total Lesion Count
Change From Baseline in Total Lesion Count.
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acne Treatment | Change From Baseline in Total Lesion Count | Week 4 | -43.7 change in lesions | Standard Deviation 39.4 |
| Acne Treatment | Change From Baseline in Total Lesion Count | Week 8 | -59.4 change in lesions | Standard Deviation 46.5 |
| Acne Treatment | Change From Baseline in Total Lesion Count | Week 12 | -69.2 change in lesions | Standard Deviation 49.6 |
Secondary
Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates
At each visit, subjects were evaluated by the investigator to determine whether (in the opinion of the investigator) they would consider them as candidates for oral isotretinoin therapy. The outcome measure reports the number and % of subjects who, in the opinion of the investigator, were not considered to be a candidate for oral isotretinoin therapy.
Time frame: Weeks 0, 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acne Treatment | Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates | Week 0 | 0 Participants |
| Acne Treatment | Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates | Week 4 | 78 Participants |
| Acne Treatment | Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates | Week 8 | 121 Participants |
| Acne Treatment | Investigator's Evaluation: Number of Subjects Not Considered to be Oral Isotretinoin Candidates | Week 12 | 149 Participants |
Secondary
Number and Percent of Adverse Events
Number and percent of subjects with any Treatment-Related Adverse Event
Time frame: Week 12
Population: The Safety Population consisted of the ITT Population following exclusion of subjects who never took the treatment with certainty, based on drug accountability data. All safety analyses were summarized for the Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acne Treatment | Number and Percent of Adverse Events | 27 Participants |
Secondary
Number and Percent of Subjects With IGA Success
IGA Success is defined as an IGA rating of Clear (Grade 0) or Almost Clear (Grade 1)
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acne Treatment | Number and Percent of Subjects With IGA Success | Week 4 | 9 Participants |
| Acne Treatment | Number and Percent of Subjects With IGA Success | Week 8 | 44 Participants |
| Acne Treatment | Number and Percent of Subjects With IGA Success | Week 12 | 69 Participants |
Secondary
Percent Change From Baseline in Inflammatory Lesion Count
Percent Change From Baseline in Inflammatory Lesion Count.
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acne Treatment | Percent Change From Baseline in Inflammatory Lesion Count | Week 4 | -38.5 percent change in lesions | Standard Deviation 37.9 |
| Acne Treatment | Percent Change From Baseline in Inflammatory Lesion Count | Week 8 | -55.0 percent change in lesions | Standard Deviation 31.9 |
| Acne Treatment | Percent Change From Baseline in Inflammatory Lesion Count | Week 12 | -66.2 percent change in lesions | Standard Deviation 30.5 |
Secondary
Percent Change From Baseline in Non-Inflammatory Lesion Count
Percent Change From Baseline in Non-Inflammatory Lesion Count.
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acne Treatment | Percent Change From Baseline in Non-Inflammatory Lesion Count | Week 4 | -34.6 percent change in lesions | Standard Deviation 45.6 |
| Acne Treatment | Percent Change From Baseline in Non-Inflammatory Lesion Count | Week 8 | -50.2 percent change in lesions | Standard Deviation 36.9 |
| Acne Treatment | Percent Change From Baseline in Non-Inflammatory Lesion Count | Week 12 | -58.7 percent change in lesions | Standard Deviation 38.8 |
Secondary
Percent Change From Baseline in Total Lesion Count
Percent Change From Baseline in Total Lesion Count.
Time frame: Weeks 4, 8, and 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population. Baseline lesion counts missing for one patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acne Treatment | Percent Change From Baseline in Total Lesion Count | Week 4 | -38.9 percent change in lesions | Standard Deviation 28.5 |
| Acne Treatment | Percent Change From Baseline in Total Lesion Count | Week 8 | -53.9 percent change in lesions | Standard Deviation 30.3 |
| Acne Treatment | Percent Change From Baseline in Total Lesion Count | Week 12 | -62.6 percent change in lesions | Standard Deviation 31.9 |
Secondary
Subject Assessment of Acne Improvement
Subject Assessment of Acne Improvement on a 6 point scale (0 = Complete Improvement, 1 = Marked Improvement, 2 = Moderate Improvement, 3 = Minimal Improvement, 4 = No Change, 5 = Worse).
Time frame: Week 12
Population: Intent-to-Treat (ITT) Population: The ITT Population consisted of the entire population enrolled at Baseline. All efficacy data were analyzed for the ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acne Treatment | Subject Assessment of Acne Improvement | 1.3 score on a scale | Standard Deviation 0.9 |