Acne
Conditions
Brief summary
The objective of this study was to evaluate the efficacy, safety, and tolerability of a once daily topical application of IDP-121 Lotion compared with its vehicle (IDP-121 Vehicle Lotion) in participants with moderate to severe acne vulgaris (acne) (that is, acne having an Evaluator's Global Severity Score \[EGSS\] of 3 \[moderate\] or 4 \[severe\]).
Interventions
DRUGIDP 121 Lotion
IDP-121 lotion will be applied as per the instructions provided by the investigational center staff.
IDP-121 vehicle lotion will be applied as per the instructions provided by the investigational center staff.
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female at least 9 years of age and older. * Written and verbal informed consent must be obtained. Participants less than age of consent must sign an assent for the study and a parent or a legal guardian must sign the informed consent (if participant reaches age of consent during the study they should be re-consented at the next study visit). * Participants must be willing to comply with study instructions and return to the study center for required visits. Participants under the age of consent must be accompanied by the parent or legal guardian at the time of assent/consent signing. * If a cleanser, moisturizer or sunscreen is needed during the study, participants must be willing to use only allowed cleansers, moisturizers, sunscreens, or moisturizer/sunscreen combination products. If the participant wears makeup they must agree to use non-comedogenic makeup. Key
Exclusion criteria
* Use of an investigational drug or device within 30 days of enrollment or participation in a research study concurrent with this study. * Any dermatological conditions on the face that could interfere with clinical evaluations such as acne conglobata, acne fulminans, secondary acne, perioral dermatitis, clinically significant rosacea, gramnegative folliculitis. * Any underlying disease(s) or some other dermatological condition of the face that requires the use of interfering topical or systemic therapy or makes evaluations and lesion count inconclusive. * Participants with a facial beard or mustache that could interfere with the study assessments. * History of hypersensitivity or allergic reactions to any of the study preparations as described in the Investigator's Brochure, including known sensitivities to any dosage form of tretinoin. * Participants who are unable to communicate or cooperate with the Investigator due to language problems, poor mental development, or impaired cerebral function. * Participants with any underlying disease that the Investigator deems uncontrolled, and poses a concern for the participant's safety while participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Mean Noninflammatory Lesion Count to Week 12 | Baseline (Day 0), Week 12 | Noninflammatory lesions were defined as follows: Open comedones (blackhead) - plugged hair follicle with dilated/open orifice, black in color; and Closed comedones (whitehead) - plugged hair follicle: small opening at skin surface. For noninflammatory facial lesions, open and closed comedones were recorded as a single count. |
| Absolute Change From Baseline in Mean Inflammatory Lesion Count to Week 12 | Baseline, Week 12 | Inflammatory lesions were defined as follows: Papule - a solid, elevated lesion less than 5 millimeters (mm); and Pustule - an elevated lesion containing pus less than 5 mm. For inflammatory facial lesions, papules and pustules were recorded as a single count, while nodular lesions were counted and recorded separately. |
| Percentage of Participants With Treatment Success at Week 12 | Baseline, Week 12 | Treatment success was defined as at least a 2-grade reduction from Baseline in EGSS score and an EGSS score equating to Clear or Almost Clear. EGSS was based on a 5-point scale ranging from 0 to 4; where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Noninflammatory Lesion Count to Week 12 | Baseline, Week 12 | Noninflammatory lesions were defined as follows: Open comedones (blackhead) - plugged hair follicle with dilated/open orifice, black in color; and Closed comedones (whitehead) - plugged hair follicle: small opening at skin surface. For noninflammatory facial lesions, open and closed comedones were recorded as a single count. |
| Percent Change From Baseline in Inflammatory Lesion Count to Week 12 | Baseline, Week 12 | Inflammatory lesions were defined as follows: Papule - a solid, elevated lesion less than 5 millimeters (mm); and Pustule - an elevated lesion containing pus less than 5 mm. For inflammatory facial lesions, papules and pustules were recorded as a single count, while nodular lesions were counted and recorded separately. |
Countries
United States
Participant flow
Pre-assignment details
Participants were randomized in a 1:1 ratio to receive either IDP-121(tretinoin 0.05 percent \[%\]) Lotion or IDP-121 Vehicle Lotion.
Participants by arm
| Arm | Count |
|---|---|
| IDP-121 Lotion IDP-121 lotion (tretinoin 0.05%) was applied topically to the face of participants with moderate to severe acne, once daily for 12 weeks. | 413 |
| IDP-121 Vehicle Lotion IDP-121 lotion vehicle was applied topically to the face of participants with moderate to severe acne, once daily for 12 weeks. | 407 |
| Total | 820 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 40 | 18 |
| Overall Study | Noncompliance with Study Drug | 1 | 1 |
| Overall Study | Participant ran out of study drug | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Subject Request | 22 | 13 |
| Overall Study | Withdrawal by Parent or Guardian | 3 | 6 |
| Overall Study | Worsening Condition | 0 | 2 |
Baseline characteristics
| Characteristic | IDP-121 Vehicle Lotion | Total | IDP-121 Lotion |
|---|---|---|---|
| Age, Continuous | 20.7 years STANDARD_DEVIATION 7.63 | 20.6 years STANDARD_DEVIATION 7.42 | 20.5 years STANDARD_DEVIATION 7.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 227 Participants | 452 Participants | 225 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 180 Participants | 367 Participants | 187 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Evaluator's Global Severity Score (EGSS) 0 - Clear | 0 Participants | 0 Participants | 0 Participants |
| Evaluator's Global Severity Score (EGSS) 1 - Almost Clear | 0 Participants | 0 Participants | 0 Participants |
| Evaluator's Global Severity Score (EGSS) 2 - Mild | 0 Participants | 0 Participants | 0 Participants |
| Evaluator's Global Severity Score (EGSS) 3 - Moderate | 356 Participants | 725 Participants | 369 Participants |
| Evaluator's Global Severity Score (EGSS) 4 - Severe | 51 Participants | 95 Participants | 44 Participants |
| Inflammatory Lesion Count | 26.0 lesion Count STANDARD_DEVIATION 5.25 | 26.2 lesion Count STANDARD_DEVIATION 5.34 | 26.5 lesion Count STANDARD_DEVIATION 5.42 |
| Noninflammatory Lesion Count | 48.3 lesion count STANDARD_DEVIATION 19.91 | 47.2 lesion count STANDARD_DEVIATION 19.6 | 46.1 lesion count STANDARD_DEVIATION 19.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 29 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 71 Participants | 161 Participants | 90 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 311 Participants | 608 Participants | 297 Participants |
| Sex: Female, Male Female | 229 Participants | 433 Participants | 204 Participants |
| Sex: Female, Male Male | 178 Participants | 387 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 389 | 0 / 398 |
| other Total, other adverse events | 0 / 389 | 0 / 398 |
| serious Total, serious adverse events | 2 / 389 | 2 / 398 |
Outcome results
Primary
Absolute Change From Baseline in Mean Inflammatory Lesion Count to Week 12
Inflammatory lesions were defined as follows: Papule - a solid, elevated lesion less than 5 millimeters (mm); and Pustule - an elevated lesion containing pus less than 5 mm. For inflammatory facial lesions, papules and pustules were recorded as a single count, while nodular lesions were counted and recorded separately.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who received study drug. Multiple imputation (MCMC) was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDP-121 Lotion | Absolute Change From Baseline in Mean Inflammatory Lesion Count to Week 12 | -13.9 lesion count | Standard Deviation 11.99 |
| IDP-121 Vehicle Lotion | Absolute Change From Baseline in Mean Inflammatory Lesion Count to Week 12 | -10.7 lesion count | Standard Deviation 12.12 |
Comparison: Analysis was performed using ANCOVA with factors of treatment group and analysis center and the respective baseline lesion count as a covariate.p-value: <0.001ANCOVA
Primary
Absolute Change From Baseline in Mean Noninflammatory Lesion Count to Week 12
Noninflammatory lesions were defined as follows: Open comedones (blackhead) - plugged hair follicle with dilated/open orifice, black in color; and Closed comedones (whitehead) - plugged hair follicle: small opening at skin surface. For noninflammatory facial lesions, open and closed comedones were recorded as a single count.
Time frame: Baseline (Day 0), Week 12
Population: ITT population included all randomized participants who received study drug. Multiple imputation (Markov Chain Monte Carlo \[MCMC\]) was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDP-121 Lotion | Absolute Change From Baseline in Mean Noninflammatory Lesion Count to Week 12 | -21.9 lesion count | Standard Deviation 22.7 |
| IDP-121 Vehicle Lotion | Absolute Change From Baseline in Mean Noninflammatory Lesion Count to Week 12 | -13.9 lesion count | Standard Deviation 23.3 |
Comparison: Analysis was performed using analysis of covariance (ANCOVA) with factors of treatment group and analysis center and the respective baseline lesion count as a covariate.p-value: <0.001ANCOVA
Primary
Percentage of Participants With Treatment Success at Week 12
Treatment success was defined as at least a 2-grade reduction from Baseline in EGSS score and an EGSS score equating to Clear or Almost Clear. EGSS was based on a 5-point scale ranging from 0 to 4; where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who received study drug and evaluable for EGSS score. Multiple imputation (MCMC) was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDP-121 Lotion | Percentage of Participants With Treatment Success at Week 12 | 19.8 percentage of participants |
| IDP-121 Vehicle Lotion | Percentage of Participants With Treatment Success at Week 12 | 12.5 percentage of participants |
Comparison: Analysis was performed using a logistic regression test (using Firth's Penalized Likelihood) with factors of treatment group and analysis center.p-value: 0.007Regression, Logistic
Secondary
Percent Change From Baseline in Inflammatory Lesion Count to Week 12
Inflammatory lesions were defined as follows: Papule - a solid, elevated lesion less than 5 millimeters (mm); and Pustule - an elevated lesion containing pus less than 5 mm. For inflammatory facial lesions, papules and pustules were recorded as a single count, while nodular lesions were counted and recorded separately.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who received study drug. Multiple imputation (MCMC) was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDP-121 Lotion | Percent Change From Baseline in Inflammatory Lesion Count to Week 12 | -53.4 percent change | Standard Deviation 45.44 |
| IDP-121 Vehicle Lotion | Percent Change From Baseline in Inflammatory Lesion Count to Week 12 | -41.5 percent change | Standard Deviation 45.68 |
Secondary
Percent Change From Baseline in Noninflammatory Lesion Count to Week 12
Noninflammatory lesions were defined as follows: Open comedones (blackhead) - plugged hair follicle with dilated/open orifice, black in color; and Closed comedones (whitehead) - plugged hair follicle: small opening at skin surface. For noninflammatory facial lesions, open and closed comedones were recorded as a single count.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who received study drug. Multiple imputation (MCMC) was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDP-121 Lotion | Percent Change From Baseline in Noninflammatory Lesion Count to Week 12 | -45.6 percent change | Standard Deviation 44.64 |
| IDP-121 Vehicle Lotion | Percent Change From Baseline in Noninflammatory Lesion Count to Week 12 | -31.9 percent change | Standard Deviation 45.79 |