A Study of PRCL-02 in Healthy Volunteers and Plaque Psoriasis

Study Overview
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Brief Summary
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This study consists of three parts: single oral dose escalation in healthy volunteers (Part A), and multiple oral dose escalations in healthy volunteers (Part B) and in participants with chronic plaque psoriasis (Part C)

Official Title
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Randomized, Double Blind, Placebo Controlled, Incomplete Crossover Single Oral Dose Escalation of PRCL-02 in Normal Healthy Volunteers (Part A) and Multiple Oral Dose Escalation in Normal Healthy Volunteers (Part B) and in Chronic Plaque Psoriasis Patients (Part C)

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: PRCL-02
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parts A and B Be 18 to 55 years old Be healthy with absence of clinically significant illness Male participants must agree to use medically accepted methods of contraception with all sexual partners during the study, and for 90 days after Female participants must be postmenopausal or surgically sterile Have venous access sufficient for blood sampling Be a non-smoker Part C Be 18 to 75 years old Have chronic plaque psoriasis based on a confirmed diagnosis of plaques for at least 6 months Have at least 2 evaluable plaques located in at least 2 body regions Exclusion Criteria: Parts A and B Significant abnormalities in vital signs, laboratory tests, electrocardiogram, or history of heart disease, some allergies, or infections Hepatic or renal impairment Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) Female participants who are pregnant or breast feeding Recent or ongoing infection History of alcohol or drug abuse Current or recent enrollment in a clinical trial judged not compatible with this study Part C Have highly active psoriatic arthritis Have pustular, erythrodermic and/or guttate forms of psoriasis Have had a clinically-significant flare of psoriasis during the last 12 weeks Currently or recently taking certain prescribed therapies for psoriasis Use of selected topical treatments within 4 weeks prior to starting the study (use of some emollients without urea is allowed, except on one lesion for biopsy)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Dose<br>Two escalating sequences of single oral doses of PRCL-02, in 3 periods, starting at 4 milligrams (mg) | Drug: PRCL-02<br>* Oral tablet(s) administered with water<br>|
| Placebo Comparator: Part A: Single Dose (Placebo)<br>Two escalating sequences of matching placebo oral tablets, in 3 periods | Drug: Placebo Oral Tablet<br>* Administered with water<br>|
| Experimental: Part B: Multiple Dose<br>Multiple oral doses of PRCL-02 for 28 days, at up to 3 dose levels | Drug: PRCL-02<br>* Oral tablet(s) administered with water<br>|
| Placebo Comparator: Part B: Multiple Dose (Placebo)<br>Multiple oral doses of placebo for 28 days, at matching dose levels | Drug: Placebo Oral Tablet<br>* Administered with water<br>|
| Experimental: Part C: Multiple Dose<br>Multiple oral doses of PRCL-02 for 28 days, at up to 3 dose levels | Drug: PRCL-02<br>* Oral tablet(s) administered with water<br>|
| Placebo Comparator: Part C: Multiple Dose (Placebo)<br>Multiple oral doses of placebo for 28 days, at matching dose levels | Drug: Placebo Oral Tablet<br>* Administered with water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Events (Part A) | Number of participants with a serious adverse event, regardless of causality, by dose and treatment | Baseline up to approximately 45 days | 
| Number of Participants with One or More Serious Adverse Events (Part B) | Number of participants with a serious adverse event, regardless of causality, by dose and treatment | Baseline up to approximately 50 days | 
| Number of Participants with One or More Serious Adverse Events (Part C) | Number of participants with a serious adverse event, regardless of causality, by dose and treatment | Baseline up to approximately 73 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Triplicate 12-lead Electrocardiogram (ECG) in Part A | Mean change from baseline in triplicate 12-lead electrocardiogram (ECG) | Baseline up to 24 hours post-dose on day 2 | 
| Change in Baseline in Triplicate 12-lead ECG in Part B | Mean change from baseline in triplicate 12-lead ECG | Baseline up to 24 hours post-dose on day 6 | 
| Change in Baseline in Triplicate 12-lead ECG in Part C | Mean change from baseline in triplicate 12-lead ECG | Baseline up to approximately day 28 | 
| Change from Baseline in Single 12-Lead ECG in Part A | Mean change from baseline in single 12-lead ECG | Baseline up to approximately 45 days | 
| Change from Baseline in Single 12-Lead ECG in Part B | Mean change from baseline in single 12-lead ECG | Baseline up to approximately 50 days | 
| Change from Baseline in Single 12-Lead ECG in Part C | Mean change from baseline in single 12-lead ECG | Baseline up to approximately 73 days | 
| Number of Participants With Clinically Significant Changes in Vital Signs in Part A | Respiration Rate, Heart Rate, Blood Pressure, Temperature | Baseline up to approximately 45 days | 
| Number of Participants With Clinically Significant Changes in Vital Signs in Part B | Respiration Rate, Heart Rate, Blood Pressure, Temperature | Baseline up to approximately 50 days | 
| Number of Participants With Clinically Significant Changes in Vital Signs in Part C | Respiration Rate, Heart Rate, Blood Pressure, Temperature | Baseline up to approximately 73 days | 
| Number of participants with Physical Examination Findings in Part A | Abnormal physical exam findings | Baseline up to approximately 45 days | 
| Number of participants with Physical Examination Findings in Part B | Abnormal physical exam findings | Baseline up to approximately 50 days | 
| Number of participants with Physical Examination Findings in Part C | Abnormal physical exam findings | Baseline up to approximately 73 days | 
| Number of participants with Laboratory Test Results outside of reference range in Part A | Laboratory results outside of reference range | Baseline up to approximately 45 days | 
| Number of participants with Laboratory Test Results outside of reference range in Part B | Laboratory results outside of reference range | Baseline up to approximately 50 days | 
| Number of participants with Laboratory Test Results outside of reference range in Part C | Laboratory results outside of reference range | Baseline up to approximately 73 days | 
| Maximum Observed Drug Concentration (Cmax) in Part A | Maximum observed plasma concentration of PRCL-02 | Baseline up to approximately 29 days | 
| Maximum Observed Drug Concentration (Cmax) in Part B | Maximum observed plasma concentration of PRCL-02 | Baseline up to approximately 33 days | 
| Maximum Observed Drug Concentration (Cmax) in Part C | Maximum observed plasma concentration of PRCL-02 | Baseline up to approximately 31 days | 
| Time to Maximum Drug Concentration (Tmax) in Part A | Time to maximum plasma concentration of PRCL-02 | Baseline up to approximately 29 days | 
| Time to Maximum Drug Concentration (Tmax) in Part B | Time to maximum plasma concentration of PRCL-02 | Baseline up to approximately 33 days | 
| Time to Maximum Drug Concentration (Tmax) in Part C | Time to maximum plasma concentration of PRCL-02 | Baseline up to approximately 31 days | 
| Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) in Part A | Area under the plasma concentration-time curve from time 0 to infinity | Baseline up to approximately 29 days | 
| Area Under the Plasma Concentration-Time Curve During the Dosing Interval (24h) (AUC0-tau) in Part B | Area under the plasma concentration-time curve during the dosing interval of 24 hours (24h) | Baseline up to approximately 33 days | 
| Area Under The Plasma Concentration-Time Curve During the Dosing Interval (24h) (AUC0-tau) in Part C | Area under the plasma concentration-time curve during the dosing interval (24h) | Baseline up to approximately 31 days | 
| Minimum or Trough Concentration (Cmin) | Minimum or trough concentration of PRCL-02 | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Lag Time: Time Delay Between Drug Administration and First Observed Plasma Concentration (Tlag) | Time delay between administration of PRCL-02 and first observed plasma concentration | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Elimination Rate (Ke) | Elimination rate of PRCL-02 | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Terminal Elimination Half-Life (t1/2) | Terminal elimination half-life of PRCL-02 | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Area Under the Plasma Concentration Time Curve from Time Zero to 24 Hours Post-dose (AUC0-24) | Area under the plasma concentration time curve from time zero to 24 hours | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Area Under the Plasma Concentration Time Curve from Time Zero to the Last Observed Time Point (AUC0-t) | Area under the plasma concentration time curve from time zero to the last observed time point | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Apparent Clearance (CL/F) | Apparent clearance of PRCL-02 | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Apparent Volume of Distribution (Vd/F) | Apparent volume of distribution of PRCL-02 | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) | 
| Accumulation Ratio | Accumulation ratio of PRCL-02 | Predose up to approximately 29 days (Part A); 33 days (Part B), 31 days (Part C) |