An Ascending Multiple Dose Study With VTP-43742 in Healthy Volunteers and Psoriatic Patients

A Randomized, Double-Blind, Placebo-Controlled Ascending Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VTP-43742 in Healthy Volunteers and Psoriatic Patients and Clinical Proof-of-Concept in Psoriatic Patients

This is a two-part, randomized, double-blind, placebo-controlled study in which VTP-43742 will be administered to normal healthy volunteers (NHV) and to moderate to severe psoriatic patients, both in sequential ascending dose panels.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Placebo 1; Drug: VTP-43742; Drug: Placebo 2

Detailed Description

This is a prospective, randomized, double-blind, placebo-controlled, ascending multiple dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics effects of VTP-43742 in healthy volunteers conducted at a single, study center and in patients with moderate to severe chronic plaque-type psoriasis at approximately 8 study centers in the United States. A total of 108 participants will be enrolled in the study (48 healthy subjects and 60 psoriatic patients).

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Patient Site 5
  • Florida
    • Miami, Florida, United States, 33144
      • Patient Site 1
    • Tampa, Florida, United States, 33609
      • Patient Site 8
    • Tampa, Florida, United States, 33624
      • Patient 12
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Patient Site 13
    • Plainfield, Indiana, United States, 46168
      • Patient Site 4
  • New Jersey
    • Fair Lawn, New Jersey, United States, 07410
      • Healthy Volunteer Site 1
  • New York
    • New York, New York, United States, 10012
      • Patient Site 2
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • Patient Site 9
  • Texas
    • College Station, Texas, United States, 77845
      • Patient Site 6
    • Dallas, Texas, United States, 75231
      • Patient Site 3
    • Houston, Texas, United States, 77004
      • Patient Site 10
    • Houston, Texas, United States, 77065
      • Patient Site 11
    • Webster, Texas, United States, 77598
      • Patient Site 7

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Healthy Volunteer Inclusion Criteria:

• Healthy males or females, 18 to 45 years of age, inclusive.
• Body weight of at least 55 kg and body mass index of 18-32 kg/m2, inclusive.
• Medically healthy with clinically insignificant screening results.
• Women of child-bearing potential (WOCBP) may be enrolled if they agree to use two of the reliable forms of contraception
• Men with partners who are WOCBP must agree that they and/or their partner will use two of the reliable forms of contraception
• WOCBP must have a negative serum βhCG pregnancy test at the Check-in visit.
• Voluntarily consent to participate in the trial

Psoriasis Patient Inclusion Criteria:

• Confirmed diagnosis of chronic plaque-type psoriasis, diagnosed at least 6 months before study with at least moderate severity, which is defined as PASI≥10, PGA≥3, and % BSA≥8
• Otherwise medically healthy and with otherwise clinically insignificant screening laboratory test results
• Males or females, 18 to 75 years of age, inclusive
• Body weight of at least 55 kg and body mass index of 18-35 kg/m2, inclusive.
• WOCBP may be enrolled if they agree to use two of the reliable forms of contraception
• Men with partners who are WOCBP must agree that they and/or their partner will use two of the reliable forms of contraception
• WOCBP must have a negative serum β hCG pregnancy test at the Screening and Baseline visit
• Voluntarily consent to participate in the trial

Healthy Volunteer Exclusion Criteria:

• Unwilling or unable to provide written informed consent
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, coagulation, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• Evidence of organ dysfunction or any clinically significant deviation from normal in vital signs, physical examination, clinical laboratory determinations or ECG
• Any major surgery within 3 months of Screening
• Positive urine drug/alcohol testing at Screening or Baseline visit
• Use of tobacco and/or nicotine-containing products within 3 months prior to the start of dosing of the trial
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV Ab) at Screening
• History or presence of alcoholism or drug abuse as defined in DSM V, Diagnostic Criteria for Drug and Alcohol Abuse
• History of hypersensitivity or idiosyncratic reaction to drugs from multiple drug classes
• Any previous gastrointestinal surgery or recent (within 3 months) history of gastrointestinal disease that could impact the absorption of the study drug
• Blood donation or significant blood loss within 8 weeks prior to Day 1of the trial
• Plasma donation within 7 days prior to Day 1 of the trial
• Blood transfusion within 4 weeks of Screening
• Positive serum pregnancy test (WOCBP) at the Screening or Baseline visit
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical disease (e.g., infectious disease) must not be enrolled into this study
• Any other medical, psychiatric, and /or social reason as determined by the Investigator

Psoriatic Patient Exclusion Criteria:

• Unwilling or unable to provide written informed consent
• Efficacy failure on two or more biological agents for the treatment of psoriasis when the failures occurred within one year of the initiation of the therapy of the first biological agent
• Current treatment or history of treatment for psoriasis with biologicals within 6 months of study Day 1
• Current treatment or history of treatment for psoriasis with non-biological systemic medications within 4 weeks of Day 1 and treatment with topical agents within 2 weeks of Day 1
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, coagulation, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• Evidence of organ dysfunction or any clinically significant deviation from normal in vital signs, physical examination, clinical laboratory determinations or ECG
• Any major surgery within 3 months of Screening
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV Ab) at Screening
• History or presence of alcoholism or drug abuse as defined in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse
• History of hypersensitivity or idiosyncratic reaction to drugs from multiple drug classes
• Any previous gastrointestinal surgery or recent (within 3 months) history of gastrointestinal disease that could impact the absorption of the study drug
• Blood donation or significant blood loss within 8 weeks prior to Day 1 of the trial
• Plasma donation within 7 days prior to Day 1 of the trial
• Blood transfusion within 4 weeks of Screening
• Positive serum pregnancy test (WOCBP) at the Screening or positive urine pregnancy test with confirmatory serum pregnancy test on Day 1
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical disease (e.g., infectious disease) must not be enrolled into this study.
• Any other medical, psychiatric, and /or social reason as determined by the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo 1; healthy volunteers	Drug: Placebo 1; Placebo 1 matching VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 1; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 2; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 3; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 4; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 5; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 6; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 7; healthy volunteers	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Placebo Comparator: Placebo 2; psoriatic patients	Drug: Placebo 2; Placebo 2 matching VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 8; psoriatic patients	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 9; psoriatic patients	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 10; psoriatic patients	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily
Experimental: VTP-43742 Dose 11; psoriatic patients	Drug: VTP-43742; VTP-43742 administered as an oral capsule once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety data, including AEs, laboratory evaluations, ECG results, and vital signs assessments, will be listed by subject and summarized by dose and time point	10 days
safety data, including AEs, laboratory evaluations, ECG results, and vital signs assessments, will be listed by subject and summarized by dose and time point	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax) will be summarized using descriptive statistics by visit and dose level	Day 1, 10 and 28
Time to maximum plasma concentrations (tmax) will be summarized using descriptive statistics by visit and dose level	Day 1, 10 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	Day 1, 10 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	Day 1, 10 and 28
Half life (t½) will be summarized using descriptive statistics by visit and dose level	Day 1, 10 and 28
Percent change from baseline in total PASI will be summarized using descriptive statistics by visit and dose level	28 days

Other Outcome Measures

Outcome Measure	Time Frame
changes from baseline and/or placebo for IL-17 plasma levels	Day 1, 10 and 28

Collaborators and Investigators

• Sponsor: Vitae Pharmaceuticals Inc., an Allergan affiliate
• Investigators: Study Director: Richard Gregg, MD, Vitae Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 15, 2015
• First Submitted That Met QC Criteria: September 18, 2015
• First Posted (Estimate): September 21, 2015

Study Record Updates

• Last Update Posted (Actual): October 30, 2018
• Last Update Submitted That Met QC Criteria: October 26, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: VTP-43742-002