Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02655679
Recruitment Status : Completed
First Posted : January 14, 2016
Results First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Vitae Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE January 11, 2016
First Posted Date  ICMJE January 14, 2016
Results First Submitted Date  ICMJE January 18, 2019
Results First Posted Date  ICMJE February 15, 2019
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE December 15, 2015
Actual Primary Completion Date September 9, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2019)
  • Number of Participants With Treatment-related Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
  • Number of subjects with treatment-related AEs listed by subject and summarized by dose and time point [ Time Frame: Day 28 ]
  • Number of subjects with abnormal laboratory values listed by subject and summarized by dose and time point [ Time Frame: Day 28 ]
  • Number of subjects with abnormal vital signs listed by subject and summarized by dose and time point [ Time Frame: Day 28 ]
  • Number of subjects with abnormal ECG values listed by subject and summarized by dose and time point [ Time Frame: Day 28 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2019)
  • 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) ]
  • Time to Maximum Plasma Concentrations (Tmax) 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Percentage Change From Baseline in Total Body Surface Area (BSA) [ Time Frame: 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 [ Time Frame: 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.
  • Percentage Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score [ Time Frame: 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.
  • Percentage Change From Baseline Eczema Area and Severity Index (EASI) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2016)
  • Maximum plasma concentration (Cmax) will be summarized using descriptive statistics by visit and dose level [ Time Frame: Days 0 and 28 ]
  • Time to maximum plasma concentrations (tmax) will be summarized using descriptive statistics by visit and dose level [ Time Frame: Days 0 and 28 ]
  • The area under the plasma concentration versus time curve, from time 0 to the last measurable concentration (AUCt) will be summarized using descriptive statistics by visit and dose level [ Time Frame: Days 0 and 28 ]
  • The area under the plasma concentration versus time curve, from time 0 to infinity (by extrapolation) (AUC∞) will be summarized using descriptive statistics by visit and dose level [ Time Frame: Days 0 and 28 ]
  • Half life (t½) will be summarized using descriptive statistics by visit and dose level [ Time Frame: Days 0 and 28 ]
  • Percent change from baseline in total BSA will be summarized using descriptive statistics by visit and dose level. [ Time Frame: Days 0 and 28 ]
  • Percent change from baseline in IGA will be summarized using descriptive statistics by visit and dose level. [ Time Frame: Days 0 and 28 ]
  • Percent change from baseline in SCORAD will be summarized using descriptive statistics by visit and dose level. [ Time Frame: Days 0 and 28 ]
  • Percent change from baseline EASI will be summarized using descriptive statistics by visit and dose level. [ Time Frame: Days 0 and 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Ascending Multiple Dose Study of VTP-38543 in Adult Participants With Mild to Moderate Atopic Dermatitis
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Dermatitis, Atopic
Intervention  ICMJE
  • Drug: VTP-38543
    VTP-38543 topical cream
  • Other: Vehicle with Transcutol®P
    Vehicle matching VTP-38543 cream with Transcutol®P
    Other Name: Transcutol®P is Diethylene Glycol Monoethyl Ether, NF.
  • Other: Vehicle without Transcutol®P
    Vehicle matching VTP-38543 cream without Transcutol®P
    Other Name: Transcutol®P is Diethylene Glycol Monoethyl Ether, NF.
Study Arms  ICMJE
  • Experimental: VTP-38543 0.05%
    VTP-38543 0.05% administered topically every 12 hours for 28 days.
    Intervention: Drug: VTP-38543
  • Experimental: VTP-38543 0.15%
    VTP-38543 0.15% administered topically every 12 hours for 28 days.
    Intervention: Drug: VTP-38543
  • Placebo Comparator: Vehicle without Transcutol®P
    Vehicle without Transcutol®P administered topically every 12 hours for 28 days.
    Intervention: Other: Vehicle without Transcutol®P
  • Experimental: VTP-38543 1%
    VTP-38543 1% administered topically every 12 hours for 28 days.
    Intervention: Drug: VTP-38543
  • Placebo Comparator: Vehicle with Transcutol®P
    Vehicle with Transcutol®P administered topically every 12 hours for 28 days.
    Intervention: Other: Vehicle with Transcutol®P
Publications * Czarnowicki T, Dohlman AB, Malik K, Antonini D, Bissonnette R, Chan TC, Zhou L, Wen HC, Estrada Y, Xu H, Bryson C, Shen J, Lala D, Ma'ayan A, McGeehan G, Gregg R, Guttman-Yassky E. Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial. Ann Allergy Asthma Immunol. 2018 Jun;120(6):631-640.e11. doi: 10.1016/j.anai.2018.03.013. Epub 2018 Mar 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2016)
104
Original Estimated Enrollment  ICMJE
 (submitted: January 12, 2016)
100
Actual Study Completion Date  ICMJE September 9, 2016
Actual Primary Completion Date September 9, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02655679
Other Study ID Numbers  ICMJE VTP-38543-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vitae Pharmaceuticals, Inc.
Study Sponsor  ICMJE Vitae Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christy Harutunian Allergan
PRS Account Vitae Pharmaceuticals, Inc.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP