An Ascending Multiple Dose Study of VTP-38543 in Adult Participants With Mild to Moderate Atopic Dermatitis

A Randomized, Double-Blind, Vehicle-Controlled Ascending Multiple Dose and Clinical Proof-Of-Concept Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VTP-38543 in Adult Patients With Mild to Moderate Atopic Dermatitis

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02655679

Enrollment

104

Registered

2016-01-14

Start date

2015-12-15

Completion date

2016-09-09

Last updated

2019-02-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dermatitis, Atopic

Keywords

Eczema

Brief summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical efficacy of VTP-38543 administered as a cream, twice-daily, for 28 days in otherwise healthy adult male and female participants with mild to moderate atopic dermatitis.

Detailed description

This is a randomized, double-blind, vehicle-controlled study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical efficacy of VTP-38543 following twice-daily, every twelve hours (Q12h) administration for 28 days in otherwise healthy adult male and female participants with mild to moderate atopic dermatitis. Evaluation of three ascending doses in three dose panels is planned for this trial. Dose Panel 1 (VTP-38543 0.05%) and Panel 2 (VTP-38543 0.15%) will each enroll 30 participants and randomize 20 to VTP-38543 and 10 to matching vehicle control (Vehicle without Transcutol®P). Dose Panel 3 (VTP-38543 1%) will enroll 40 participants and randomize 20 to VTP-38543 and 20 to matching vehicle control (Vehicle with Transcutol®P). A total of approximately 100 participants will participate in the trial.

Interventions

DRUGVTP-38543

VTP-38543 topical cream

OTHERVehicle with Transcutol®P

Vehicle matching VTP-38543 cream with Transcutol®P

OTHERVehicle without Transcutol®P

Vehicle matching VTP-38543 cream without Transcutol®P

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Mild to moderate atopic dermatitis with a minimum of 3 to a maximum of 15% body surface area (BSA) involvement * Investigator Global Assessments (IGA) score of 2 or 3 * Body Mass Index (BMI) = 18 - 35 kg/m\^2 * Negative Pregnancy test for females

Exclusion criteria

* Treatment for atopic dermatitis with systemic medications, topical agents, and parenteral biological/monoclonal antibody agents, within specific time period prior to dosing. * Organ dysfunction or any clinically significant deviation from normal in vital signs, physical examinations, labs, and Electrocardiogram (ECG) findings * Major surgery within 3 months of Screening * Use of prescription drugs, sedative antihistamine, medical devices for treatment of atopic dermatitis (AD), and topical products containing urea and/or ceramides within 14 prior to dosing * Excessive sun exposures, use of tanning booths or other ultraviolet (UV) light sources 4 weeks prior to dosing

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-related Adverse Events (AEs)	Baseline (Day 0) to Day 35	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The number of participants with AEs related to treatment are reported.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Values	Baseline (Day 0) to Day 35	Clinical Laboratory tests included chemistry, hematology and urinalysis tests collected during the study. The investigator determined if the changes in laboratory results were clinically significant.
Number of Participants With Clinically Significant Changes in Vital Signs	Baseline (Day 0) to Day 35	Vital signs included blood pressure, pulse, respiration rate and body temperature. The investigator determined if the changes in vital sign results were clinically significant.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values	Baseline (Day 0) to Day 35	A standard 12-lead ECG was performed. The investigator determined if the changes in ECG results were clinically significant.

Secondary

Measure	Time frame	Description
Elimination Half-life (t½) for VTP-38543	Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)	—
Percentage Change From Baseline in Total Body Surface Area (BSA)	Baseline (Day 0) to Day 28	Percent BSA was estimated using the palmar surface of the participant's hand up to the proximal interphalangeal joint, including the thumb, to approximate 1% of the participant's BSA. The overall BSA affected by atopic dermatitis was evaluated from 0 to 100% and divided by 5 for a maximum of 20. A negative percentage change indicates improvement.
Percentage Change From Baseline in Investigator Global Assessments (IGA) Score	Baseline (Day 0) to Day 28	The investigator assessed the participant's atopic dermatitis using the 5-point IGA where 0=clear (Minor, residual discoloration, no erythema or induration/papulation, no oozing/crusting) to 4=Severe disease (Deep/bright red erythema with severe induration/papulation with oozing/crusting). A negative percentage change indicates improvement.
Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)	—
Percentage Change From Baseline Eczema Area and Severity Index (EASI)	Baseline (Day 0) to Day 28	The investigator assessed four body regions: Head and neck, Upper extremities, Trunk including axillae and groin, and Lower extremities including buttocks. Each body region was scored based on BSA where 0=No involvement to 6=90-100%. Each body region was assessed for erythema, infiltration/papulation, excoriation and lichenification using a 4-point scale where 0=None to 3=Severe. EASI total score was determined by combining the individual scores for each of the 4 body regions. The total for each region was calculated by \[erythema + infiltration+ excoriation + lichenification \* area involvement \* a constant (constants Head and Neck=0.1, Upper Limbs=0.2, Trunk=0.3, Lower Limbs=0.4)\]. The EASI total score was determined by combining the individual scores for each of the 4 body regions for a total possible score of 0 (best) to 72 (worst). A negative percentage change indicates improvement.
Percentage Change From Baseline in Pruritus VAS Score	Baseline (Day 0) to Day 28	The participant used a 10-point VAS to assess the occurrence of pruritus (itchy skin) over the last 3 days where 0= None to 10=Worst Imaginable for a total possible score of 0 to 10. A negative percentage change indicates improvement.
Percentage Change From Baseline in VAS Sleep Score	Baseline (Day 0) to Day 28	The participant used a 10-point VAS to evaluate loss of sleep averaged over the last 3 days where 0= None to 10=Worst imaginable for a total possible score of 0 to 10. A negative percentage change indicates improvement.
Percentage Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score	Baseline (Day 0) to Day 28	The investigator assessed severity of atopic dermatitis (AD) using scoring atopic dermatitis (SCORAD) score obtained from different individual scales. 6-items: erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness were graded on a 4-point scale where 0=Absent to 3=Severe. The individual scores were added together to get a score of 0 to 18 that was multiplied by 3.5 for a score of 0 to 63. The overall BSA affected by AD (0 to 100 %) was divided by 5 for a score 0 to 20. The participant used a 10-point Visual Analog Scale (VAS) to evaluate loss of sleep and the occurrence of pruritus averaged over the last 3 days where 0=None to Worst Imaginable. The sum of the 2 VAS scores was 0 to 20. The above measures were added together for a total possible SCORAD score of 0 (best) to 103 (worst). A negative percentage change indicates improvement.
Time to Maximum Plasma Concentrations (Tmax) for VTP-38543	Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)	—
Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)	—
Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)	—

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
VTP- 38543 0.05% VTP-38543 0.05% administered topically every 12 hours for 28 days.	20
VTP- 38543 0.15% VTP-38543 0.15% administered topically every 12 hours for 28 days.	19
Vehicle Without Transcutol®P Vehicle without Transcutol®P administered topically every 12 hours for 28 days.	20
VTP-38543 1% VTP-38543 1% administered topically every 12 hours for 28 days.	24
Vehicle With Transcutol®P Vehicle with Transcutol®P administered topically every 12 hours for 28 days.	20
Total	103

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	0	1	0	0	0
Overall Study	Inability to Comply with the Protocol	1	0	0	0	0
Overall Study	Lost to Follow-up	0	1	1	1	0
Overall Study	Other Miscellaneous Reasons	1	0	0	0	0
Overall Study	Withdrawal by Subject	1	1	0	3	1

Baseline characteristics

Characteristic	VTP- 38543 0.05%	VTP- 38543 0.15%	Vehicle Without Transcutol®P	VTP-38543 1%	Vehicle With Transcutol®P	Total
Age, Continuous	36.2 years STANDARD_DEVIATION 15.79	36.8 years STANDARD_DEVIATION 13.39	30.8 years STANDARD_DEVIATION 11.59	35.7 years STANDARD_DEVIATION 10.51	30.9 years STANDARD_DEVIATION 11.73	34.1 years STANDARD_DEVIATION 12.67
Sex: Female, Male Female	13 Participants	11 Participants	8 Participants	14 Participants	9 Participants	55 Participants
Sex: Female, Male Male	7 Participants	8 Participants	12 Participants	10 Participants	11 Participants	48 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 / 20	0 / 19	0 / 20	0 / 24	0 / 20
other Total, other adverse events	10 / 20	12 / 19	12 / 20	8 / 24	6 / 20
serious Total, serious adverse events	0 / 20	0 / 19	0 / 20	0 / 24	0 / 20

Outcome results

Primary

Number of Participants With Clinically Significant Changes in Clinical Laboratory Values

Clinical Laboratory tests included chemistry, hematology and urinalysis tests collected during the study. The investigator determined if the changes in laboratory results were clinically significant.

Time frame: Baseline (Day 0) to Day 35

Population: Safety population included randomized participants who received at least one dose of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
VTP-38543 0.05%	Number of Participants With Clinically Significant Changes in Clinical Laboratory Values	0 Participants
VTP-38543 0.15%	Number of Participants With Clinically Significant Changes in Clinical Laboratory Values	1 Participants
Vehicle Without Transcutol®P	Number of Participants With Clinically Significant Changes in Clinical Laboratory Values	0 Participants
VTP-38543 1%	Number of Participants With Clinically Significant Changes in Clinical Laboratory Values	0 Participants
Vehicle With Transcutol®P	Number of Participants With Clinically Significant Changes in Clinical Laboratory Values	0 Participants

Primary

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values

A standard 12-lead ECG was performed. The investigator determined if the changes in ECG results were clinically significant.

Time frame: Baseline (Day 0) to Day 35

Population: Safety population included randomized participants who received at least one dose of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
VTP-38543 0.05%	Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values	0 Participants
VTP-38543 0.15%	Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values	0 Participants
Vehicle Without Transcutol®P	Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values	0 Participants
VTP-38543 1%	Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values	0 Participants
Vehicle With Transcutol®P	Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values	0 Participants

Primary

Number of Participants With Clinically Significant Changes in Vital Signs

Vital signs included blood pressure, pulse, respiration rate and body temperature. The investigator determined if the changes in vital sign results were clinically significant.

Time frame: Baseline (Day 0) to Day 35

Population: Safety population included randomized participants who received at least one dose of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
VTP-38543 0.05%	Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants
VTP-38543 0.15%	Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants
Vehicle Without Transcutol®P	Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants
VTP-38543 1%	Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants
Vehicle With Transcutol®P	Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants

Primary

Number of Participants With Treatment-related Adverse Events (AEs)

An Adverse Event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The number of participants with AEs related to treatment are reported.

Time frame: Baseline (Day 0) to Day 35

Population: Safety population included randomized participants who received at least one dose of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
VTP-38543 0.05%	Number of Participants With Treatment-related Adverse Events (AEs)	1 Participants
VTP-38543 0.15%	Number of Participants With Treatment-related Adverse Events (AEs)	3 Participants
Vehicle Without Transcutol®P	Number of Participants With Treatment-related Adverse Events (AEs)	2 Participants
VTP-38543 1%	Number of Participants With Treatment-related Adverse Events (AEs)	6 Participants
Vehicle With Transcutol®P	Number of Participants With Treatment-related Adverse Events (AEs)	2 Participants

Secondary

Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543

Time frame: Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)

Population: PK population included all participants with available plasma concentration data with profiles adequate to determine PK parameters. Number analyzed is the number of participants with serial sampling data available at the given timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
VTP-38543 0.05%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 0	2.27 ng*hr/mL	Standard Deviation 4.23
VTP-38543 0.05%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 27	23.6 ng*hr/mL	Standard Deviation 44.8
VTP-38543 0.15%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 0	1.35 ng*hr/mL	Standard Deviation 1.41
VTP-38543 0.15%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 27	22.2 ng*hr/mL	Standard Deviation 18.2
Vehicle Without Transcutol®P	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 0	20.0 ng*hr/mL	Standard Deviation 28.2
Vehicle Without Transcutol®P	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to 12 Hours (AUC0-12hr) for VTP-38543	Day 27	144 ng*hr/mL	Standard Deviation 144

Secondary

Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543

Time frame: Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)

Arm	Measure	Group	Value (MEAN)	Dispersion
VTP-38543 0.05%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 0	2.27 ng*hr/mL	Standard Deviation 4.23
VTP-38543 0.05%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 27	129 ng*hr/mL	Standard Deviation 257
VTP-38543 0.15%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 0	1.35 ng*hr/mL	Standard Deviation 1.41
VTP-38543 0.15%	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 27	104 ng*hr/mL	Standard Deviation 77.5
Vehicle Without Transcutol®P	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 0	20.0 ng*hr/mL	Standard Deviation 28.2
Vehicle Without Transcutol®P	Area Under the Plasma Concentration Versus Time Curve, From Time 0 to the Last Measurable Concentration (AUClast) for VTP-38543	Day 27	720 ng*hr/mL	Standard Deviation 798

Secondary

Elimination Half-life (t½) for VTP-38543

Time frame: Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)

Population: PK Population included all participants with available plasma concentration data with profiles adequate to determine PK parameters. Number analyzed is the number of participants with serial sampling data available at the given timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
VTP-38543 0.05%	Elimination Half-life (t½) for VTP-38543	Day 0	NA hour	—
VTP-38543 0.05%	Elimination Half-life (t½) for VTP-38543	Day 27	58.6 hour	Standard Deviation 14.5
VTP-38543 0.15%	Elimination Half-life (t½) for VTP-38543	Day 0	NA hour	—
VTP-38543 0.15%	Elimination Half-life (t½) for VTP-38543	Day 27	47.2 hour	Standard Deviation 12.2
Vehicle Without Transcutol®P	Elimination Half-life (t½) for VTP-38543	Day 0	NA hour	—
Vehicle Without Transcutol®P	Elimination Half-life (t½) for VTP-38543	Day 27	246 hour	Standard Deviation 349

Secondary

Maximum Plasma Concentration (Cmax) for VTP-38543-001

Time frame: Day 0 (pre-dose, 1, 2, 4, 6, 9, and 12 hours post first dose), and Day 27 (pre-dose, 1, 2, 4, 6, 9, 12, 24, 48, and 72 hours post last dose)

Population: Pharmacokinetic (PK) population included all participants with available plasma concentration data with profiles adequate to determine PK parameters. Number analyzed is the number of participants with serial sampling data available at the given timepoint.

Arm	Measure	Group	Value (MEAN)	Dispersion
VTP-38543 0.05%	Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 0	0.546 ng/mL	Standard Deviation 1.16
VTP-38543 0.05%	Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 27	2.81 ng/mL	Standard Deviation 5.35
VTP-38543 0.15%	Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 0	0.221 ng/mL	Standard Deviation 0.175
VTP-38543 0.15%	Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 27	2.28 ng/mL	Standard Deviation 1.68
Vehicle Without Transcutol®P	Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 27	13.4 ng/mL	Standard Deviation 12.7
Vehicle Without Transcutol®P	Maximum Plasma Concentration (Cmax) for VTP-38543-001	Day 0	2.34 ng/mL	Standard Deviation 3.29

Secondary

Percentage Change From Baseline Eczema Area and Severity Index (EASI)

The investigator assessed four body regions: Head and neck, Upper extremities, Trunk including axillae and groin, and Lower extremities including buttocks. Each body region was scored based on BSA where 0=No involvement to 6=90-100%. Each body region was assessed for erythema, infiltration/papulation, excoriation and lichenification using a 4-point scale where 0=None to 3=Severe. EASI total score was determined by combining the individual scores for each of the 4 body regions. The total for each region was calculated by \[erythema + infiltration+ excoriation + lichenification \* area involvement \* a constant (constants Head and Neck=0.1, Upper Limbs=0.2, Trunk=0.3, Lower Limbs=0.4)\]. The EASI total score was determined by combining the individual scores for each of the 4 body regions for a total possible score of 0 (best) to 72 (worst). A negative percentage change indicates improvement.