Atopic Dermatitis
Conditions
Brief summary
The purpose of this study is to assess the pharmacokinetic parameters and safety of topical MM36 (OPA-15406) ointment in pediatric subjects with atopic dermatitis under maximal use conditions.
Detailed description
This is a multi-center, open-label study to assess the degree of systemic exposure and safety of MM36 1% ointment following 4 weeks of twice daily dosing under maximal-use conditions in pediatric subjects with atopic dermatitis.
Interventions
DRUGMM36 topical ointment, 1%
Twice daily application for 28 consecutive days
Sponsors
Medimetriks Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects 2 to \<18 years of age * Diagnosis of atopic dermatitis (AD) * AD affecting ≥ 35% body surface area (BSA) if 2 to \< 12 years of age or ≥ 25% if subject is ≥ 12 years of age (excluding scalp and venous access areas)
Exclusion criteria
* Active or acute viral skin infection * History of recurrent bacterial infection * Malignancy * Clinically significant history or physical findings that may pose a health risk to subject or may have an impact on study assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of MM36 | Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1 | Maximum observed plasma concentration of MM36 on Day 1 |
| Time of Maximum Observed Plasma Concentration (Tmax) of MM36 | Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1 | Time of Maximum Observed Plasma Concentration (Tmax) of MM36 on Day 1 |
| Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36 | Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1 | Area Under the Plasma Concentration-time Curve from Time Zero To the time of Last Quantifiable Plasma Concentration of MM36 on Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Application Site Adverse Events (AEs) According to Severity | up to 4 weeks | Number of Participants With Application Site Adverse Events (AEs) According to Severity. Adverse events were classified according to severity as: mild - an event that is usually transient in nature and generally not interfering with normal activities; moderate - an event that is sufficiently discomforting to interfere with normal activities; severe - an event that is incapacitating with inability to work or do usual activity or inability to work or perform normal daily activity. |
| Clinically Meaningful Laboratory Test Median Changes From Baseline | Day 29 | Number of Participants With Clinically Meaningful Laboratory Test Median Changes From Baseline. Clinical meaningfulness of laboratory test changes was determined at the investigator's discretion. |
| Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | up to 4 weeks | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| Clinically Meaningful ECG Median Changes From Baseline to Day 15 | Day 15 | Number of Participants With Clinically Meaningful ECG Median Changes from Baseline. Clinical meaningfulness of ECG changes was determined at the investigator's discretion. |
| Clinically Meaningful ECG Median Changes From Baseline to Day 29 | Day 29 | Number of Participants With Clinically Meaningful ECG Median Changes from Baseline. Clinical meaningfulness of ECG changes was determined at the investigator's discretion. |
| Clinically Meaningful Vital Sign Median Changes From Baseline | Day 29 | Number of Participants With Clinically Meaningful Vital Sign Median Changes From Baseline. Clinical meaningfulness of vital sign changes was determined at the investigator's discretion. |
| Treatment-Emergent Adverse Events (AEs) According to Severity | up to 4 weeks | Number of Participants With Treatment-Emergent Adverse Events (AEs) According to Severity. Adverse events were classified according to severity as: mild - an event that is usually transient in nature and generally not interfering with normal activities; moderate - an event that is sufficiently discomforting to interfere with normal activities; severe - an event that is incapacitating with inability to work or do usual activity or inability to work or perform normal daily activity. |
| Application Site Adverse Events (AEs) | up to 4 weeks | Number of Participants With Application Site Adverse Events (AEs) |
Countries
Honduras, Panama, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MM36 Topical Ointment, 1% MM36 topical ointment, 1%, applied twice daily for 28 days | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Parent/Guardian | 3 |
Baseline characteristics
| Characteristic | MM36 Topical Ointment, 1% |
|---|---|
| Age, Categorical <=18 years | 32 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 7.9 years STANDARD_DEVIATION 4.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Percentage of Body Surface Area (BSA) Involved | 43.7 % STANDARD_DEVIATION 13.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment Honduras | 6 participants |
| Region of Enrollment Panama | 11 participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 7 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36
Area Under the Plasma Concentration-time Curve from Time Zero To the time of Last Quantifiable Plasma Concentration of MM36 on Day 1
Time frame: Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1
Population: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36 | 107 ng·hr/mL | Standard Deviation 94.1 |
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36
Area Under the Plasma Concentration-Time Curve From Time Zero To the time of Last Quantifiable Plasma Concentration of MM36 on Day 15
Time frame: Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 15
Population: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36 | 86.2 ng·hr/mL | Standard Deviation 79.6 |
Primary
Maximum Observed Plasma Concentration (Cmax) of MM36
Maximum observed plasma concentration of MM36 on Day 1
Time frame: Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1
Population: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Maximum Observed Plasma Concentration (Cmax) of MM36 | 23.1 ng/mL | Standard Deviation 23.4 |
Primary
Maximum Observed Plasma Concentration (Cmax) of MM36
Maximum observed plasma concentration of MM36 after two weeks of twice daily application (steady state)
Time frame: Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 15
Population: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Maximum Observed Plasma Concentration (Cmax) of MM36 | 16.9 ng/mL | Standard Deviation 21.9 |
Primary
Time of Maximum Observed Plasma Concentration (Tmax) of MM36
Time of Maximum Observed Plasma Concentration (Tmax) of MM36 on Day 1
Time frame: Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 1
Population: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Time of Maximum Observed Plasma Concentration (Tmax) of MM36 | 4.22 hours | Standard Deviation 2.02 |
Primary
Time of Maximum Observed Plasma Concentration (Tmax) of MM36
Time of Maximum Observed Plasma Concentration (Tmax) of MM36 on Day 15
Time frame: Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 15
Population: Pharmacokinetic (PK) population included participants in the Safety Population with PK Data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Time of Maximum Observed Plasma Concentration (Tmax) of MM36 | 3.80 hours | Standard Deviation 2.24 |
Secondary
Application Site Adverse Events (AEs)
Number of Participants With Application Site Adverse Events (AEs)
Time frame: up to 4 weeks
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) | None | 29 participants |
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) | Application site pain | 1 participants |
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) | Application site rash | 1 participants |
Secondary
Application Site Adverse Events (AEs) According to Severity
Number of Participants With Application Site Adverse Events (AEs) According to Severity. Adverse events were classified according to severity as: mild - an event that is usually transient in nature and generally not interfering with normal activities; moderate - an event that is sufficiently discomforting to interfere with normal activities; severe - an event that is incapacitating with inability to work or do usual activity or inability to work or perform normal daily activity.
Time frame: up to 4 weeks
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) According to Severity | None | 29 participants |
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) According to Severity | Mild | 1 participants |
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) According to Severity | Moderate | 1 participants |
| MM36 Topical Ointment, 1% | Application Site Adverse Events (AEs) According to Severity | Severe | 0 participants |
Secondary
Clinically Meaningful ECG Median Changes From Baseline to Day 15
Number of Participants With Clinically Meaningful ECG Median Changes from Baseline. Clinical meaningfulness of ECG changes was determined at the investigator's discretion.
Time frame: Day 15
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MM36 Topical Ointment, 1% | Clinically Meaningful ECG Median Changes From Baseline to Day 15 | 0 participants |
Secondary
Clinically Meaningful ECG Median Changes From Baseline to Day 29
Number of Participants With Clinically Meaningful ECG Median Changes from Baseline. Clinical meaningfulness of ECG changes was determined at the investigator's discretion.
Time frame: Day 29
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MM36 Topical Ointment, 1% | Clinically Meaningful ECG Median Changes From Baseline to Day 29 | 0 participants |
Secondary
Clinically Meaningful Laboratory Test Median Changes From Baseline
Number of Participants With Clinically Meaningful Laboratory Test Median Changes From Baseline. Clinical meaningfulness of laboratory test changes was determined at the investigator's discretion.
Time frame: Day 29
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MM36 Topical Ointment, 1% | Clinically Meaningful Laboratory Test Median Changes From Baseline | 0 participants |
Secondary
Clinically Meaningful Vital Sign Median Changes From Baseline
Number of Participants With Clinically Meaningful Vital Sign Median Changes From Baseline. Clinical meaningfulness of vital sign changes was determined at the investigator's discretion.
Time frame: Day 29
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MM36 Topical Ointment, 1% | Clinically Meaningful Vital Sign Median Changes From Baseline | 0 participants |
Secondary
Treatment-Emergent Adverse Events (AEs) According to Severity
Number of Participants With Treatment-Emergent Adverse Events (AEs) According to Severity. Adverse events were classified according to severity as: mild - an event that is usually transient in nature and generally not interfering with normal activities; moderate - an event that is sufficiently discomforting to interfere with normal activities; severe - an event that is incapacitating with inability to work or do usual activity or inability to work or perform normal daily activity.
Time frame: up to 4 weeks
Population: Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) According to Severity | None | 24 participants |
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) According to Severity | Mild | 6 participants |
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) According to Severity | Moderate | 1 participants |
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) According to Severity | Severe | 0 participants |
Secondary
Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to 4 weeks
Population: Safety population included all subjects in the Intent to treat (ITT) population who had at least one post-baseline safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | No AE | 24 participants |
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 7 participants |
| MM36 Topical Ointment, 1% | Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |