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.

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).

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