Pharmacokinetics and Safety of MM36 Topical Ointment in Pediatric Subjects With Atopic Dermatitis

• Sponsor: Medimetriks Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02945657
• Collaborator: (none)
• Enrollment: 32
• Locations: 12
• Arm: 1
• Duration (Months): 8.2
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: MM36 topical ointment, 1%	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Protocol MEDI-MM36-206: A Phase 2 Multi-center, Open-label Study to Assess Pharmacokinetic Parameters and Safety of Topical MM36 (1%) in Pediatric Subjects 2 to < 18 Years of Age With Atopic Dermatitis Under Maximal Use Conditions
• Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Jun 8, 2017
• Actual Study Completion Date: Jun 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MM36 1% ointment MM36 topical ointment, 1%, applied twice daily for 28 days	Drug: MM36 topical ointment, 1%; Twice daily application for 28 consecutive days; Other Names: OPA-15406

Outcome Measures

Primary Outcome Measures

1. 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

2. Maximum Observed Plasma Concentration (Cmax) of MM36 [Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 15]

   Maximum observed plasma concentration of MM36 after two weeks of twice daily application (steady state)

3. 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

4. Time of Maximum Observed Plasma Concentration (Tmax) of MM36 [Pre-dose (0 hour), 1, 4, and 8 hours post-dose on Day 15]

   Time of Maximum Observed Plasma Concentration (Tmax) of MM36 on Day 15

5. 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

6. 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 15]

   Area Under the Plasma Concentration-Time Curve From Time Zero To the time of Last Quantifiable Plasma Concentration of MM36 on Day 15

Secondary Outcome Measures

1. 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)

2. 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.

3. Application Site Adverse Events (AEs) [up to 4 weeks]

   Number of Participants With Application Site Adverse Events (AEs)

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medimetriks Investigational Site	Fremont	California	United States	94538
2	Medimetriks Investigational Site	Irvine	California	United States	92697
3	Medimetriks Investigational Site	San Diego	California	United States	92123
4	Medimetriks Investigational Site	Miami	Florida	United States	33125
5	Medimetriks Investigational Site	Saint Joseph	Missouri	United States	64506
6	Medimetriks Investigational Site	Portland	Oregon	United States	97239
7	Medimetriks Investigational Site	Austin	Texas	United States	78759
8	Medimetriks Investigational Site	Houston	Texas	United States	77030
9	Medimetriks Investigational Site	Norfolk	Virginia	United States	23502
10	Medimetriks Investigational Site	Spokane	Washington	United States	99202
11	Medimetriks Investigational Site	San Pedro Sula		Honduras
12	Medimetriks Investigational Site	Panama City		Panama

Sponsors and Collaborators

• Medimetriks Pharmaceuticals, Inc

Investigators

• Study Director: Noah Rosenberg, MD, Medimetriks Pharmaceuticals, Inc

Study Documents (Full-Text)

• Statistical Analysis Plan - May 18, 2017
• Study Protocol - Jan 30, 2017

More Information

Publications

None provided.

• Responsible Party: Medimetriks Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT02945657
• Other Study ID Numbers: MEDI-MM36-206
• First Posted: Oct 26, 2016
• Last Update Posted: Nov 19, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

Participant Flow

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Period Title: Overall Study
STARTED	32
COMPLETED	28
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Overall Participants	32
Age (Count of Participants)
<=18 years	32 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.9 (4.33)
Sex: Female, Male (Count of Participants)
Female	16 50%
Male	16 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 62.5%
Not Hispanic or Latino	12 37.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 6.3%
Asian	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 15.6%
White	17 53.1%
More than one race	7 21.9%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 46.9%
Panama	11 34.4%
Honduras	6 18.8%
Percentage of Body Surface Area (BSA) Involved (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	43.7 (13.25)

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of MM36
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
Measure Participants	31
Mean (Standard Deviation) [ng/mL]	23.1 (23.4)

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of MM36
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
Measure Participants	31
Mean (Standard Deviation) [ng/mL]	16.9 (21.9)

3. Primary Outcome

Title	Time of Maximum Observed Plasma Concentration (Tmax) of MM36
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
Measure Participants	31
Mean (Standard Deviation) [hours]	4.22 (2.02)

4. Primary Outcome

Title	Time of Maximum Observed Plasma Concentration (Tmax) of MM36
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
Measure Participants	31
Mean (Standard Deviation) [hours]	3.80 (2.24)

5. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
Measure Participants	31
Mean (Standard Deviation) [ng·hr/mL]	107 (94.1)

6. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Plasma Concentration of MM36
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included participants in the Safety Population with PK Data

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
Measure Participants	31
Mean (Standard Deviation) [ng·hr/mL]	86.2 (79.6)

7. Secondary Outcome

Title	Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	up to 4 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the Intent to treat (ITT) population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
No AE	24 75%
AE	7 21.9%
SAE	0 0%

8. Secondary Outcome

Title	Treatment-Emergent Adverse Events (AEs) According to Severity
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
None	24 75%
Mild	6 18.8%
Moderate	1 3.1%
Severe	0 0%

9. Secondary Outcome

Title	Application Site Adverse Events (AEs)
Description	Number of Participants With Application Site Adverse Events (AEs)
Time Frame	up to 4 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
None	29 90.6%
Application site pain	1 3.1%
Application site rash	1 3.1%

10. Secondary Outcome

Title	Application Site Adverse Events (AEs) According to Severity
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
None	29 90.6%
Mild	1 3.1%
Moderate	1 3.1%
Severe	0 0%

11. Secondary Outcome

Title	Clinically Meaningful Laboratory Test Median Changes From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
Number [participants]	0 0%

12. Secondary Outcome

Title	Clinically Meaningful Vital Sign Median Changes From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
Number [participants]	0 0%

13. Secondary Outcome

Title	Clinically Meaningful ECG Median Changes From Baseline to Day 15
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
Number [participants]	0 0%

14. Secondary Outcome

Title	Clinically Meaningful ECG Median Changes From Baseline to Day 29
Description	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

Outcome Measure Data

Analysis Population Description

Safety population included all subjects in the ITT population who had at least one post-baseline safety assessment

Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 28 days
Measure Participants	31
Number [participants]	0 0%

Adverse Events

Time Frame	up to 4 weeks
Arm/Group Title	MM36 Topical Ointment, 1%
Arm/Group Description	MM36 topical ointment, 1%, applied twice daily for 15 days
All Cause Mortality
	MM36 Topical Ointment, 1%
	Affected / at Risk (%)	# Events
Total	0/31 (0%)
Serious Adverse Events
	MM36 Topical Ointment, 1%
	Affected / at Risk (%)	# Events
Total	0/31 (0%)
Other (Not Including Serious) Adverse Events
	MM36 Topical Ointment, 1%
	Affected / at Risk (%)	# Events
Total	7/31 (22.6%)
Gastrointestinal disorders
Vomiting	1/31 (3.2%)	1
General disorders
Application site pain	1/31 (3.2%)	1
Application site rash	1/31 (3.2%)	1
Influenza like illness	1/31 (3.2%)	1
Pyrexia	1/31 (3.2%)	1
Infections and infestations
Nasopharyngitis	1/31 (3.2%)	1
Tonsillitis	1/31 (3.2%)	1
Upper respiratory tract infection	1/31 (3.2%)	1
Investigations
Eosinophil count increased	1/31 (3.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Since the study is part of a multi-center study and an independent publication that will incorporate multi-center trial data is anticipated, Institution agrees not to independently publish its results of the study if such publication is published within 12 months from completion of the study. The Institution and Investigator agree not to publish the results of the study without prior written consent of the Sponsor, which consent may be withheld by Sponsor for any or no reason.