Icotinib Hydrochloride Cream in Healthy Adults and Psoriasis Patients

Study Overview
=================
Brief Summary
-----------------
This is a phase I study to evaluate the safety, tolerability and pharmacokinetics of Icotinib Hydrochloride Cream in healthy adults and patients with mild to moderate psoriasis.

Detailed Description
-----------------
Icotinib Hydrochloride is a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) in China in its oral form. As EGFR is implicated in the pathogenesis of psoriasis, icotinib hydrochloride is being developed as a cream for the treatment of mild to moderate psoriasis. This is a single-center, randomized, double-blind, placebo-controlled study of icotinib hydrochloride cream by topical administration. The study is designed in two parts in healthy subjects (part 1) followed by patients with mild to moderate psoriasis (part 2). 1% and 2% icotinib hydrochloride cream will be initially applied to healthy subjects. Once the study in healthy adults shows favorable safety and tolerability, a study in patients with mild to moderate psoriasis will be followed. Approximately 28 subjects will be enrolled, including 12 healthy subjects (Part 1) and 16 patients with psoriasis (Part 2).

Official Title
-----------------
A Single-Center, Randomized, Double-blind, Placebo-Controlled Study to Evaluate Safety, Tolerability and Pharmacokinetics of Icotinib Hydrochloride Cream in Healthy Adult Participants, Followed by Patients With Mild to Moderate Psoriasis

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Drug: 1% icotinib hydrochloride cream
* Drug: 2% icotinib hydrochloride cream
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For Part 1-Healthy Participants 18-50 years old (inclusive), male or female Male participants should be ≥ 50 kg, female participants should be ≥ 45 kg; Body Mass Index (BMI) should be between 19 and 30 kg/m2 (inclusive) In good health, with no history of diseases of major organs and no BP, HR, ECG or respiratory abnormality on physical examination Adequate hepatic and renal function, as determined by clinical laboratory assessments of blood and urine Negative serum pregnancy test at Screening and negative urine pregnancy test at Day -1 for females of child bearing potential Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen (HBsAg), hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) at screening; and negative drugs of abuse, alcohol pre dose on Day -1 Have signed a written informed consent before entering the study For Part 2 - Patients with Psoriasis Clinical diagnosis of psoriasis for at least six months with multiple affected areas (excluding the face, scalp, genitals and groin) involving 2%-15% of the total Body Surface Area (BSA) 18-65 years old Male participants should be ≥ 50 kg, female participants should be ≥ 45 kg; BMI should be between 19 and 35 kg/m2 (inclusive) In good health, with no history of diseases of major organs and no BP, HR, ECG or respiratory abnormality on physical examination Adequate hepatic and renal function, as determined by clinical laboratory assessments of blood and urine Negative serum pregnancy test at Screening and negative urine pregnancy test at Day -1 for females of child bearing potential Negative screen for drugs of abuse, alcohol, HBsAg, HCV and HIV at screening; and negative drugs of abuse, alcohol pre dose on Day1 Women of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy Have signed a written informed consent before entering the study Exclusion Criteria: For Part 1-Healthy Participants Any clinically significant central nervous system, cardiac, pulmonary, renal, gastrointestinal, respiratory, metabolic conditions (or history), or other pathological or physiological conditions that might interfere with the trial result History of postural hypotension Use of any topical agents (including non-medicated lotions such as sun screen, cosmetics, moisturizing lotion) at the administration site within a week before randomization History of serious skin diseases (as determined by the investigator); no presence of skin ulceration at the test area at the time of the Screening visit Current smoker, or a history of regular (more than weekly) use of tobacco- or nicotine-containing products within two months prior to screening History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last three months For Part 2 - Patients with Psoriasis Any clinically significant central nervous system, cardiac, pulmonary, renal, gastrointestinal, respiratory, metabolic conditions (or history), or other pathological or physiological conditions that might interfere with the trial result History of postural hypotension Use of any topical agents (including non-medicated lotions such as sun screen, cosmetics, moisturizing lotion) at the administration site within a week before randomization History of serious skin diseases (as determined by the investigator); no presence of skin ulceration at the test area at the time of the Screening visit Excessive smoker(≥10 cigarettes per day), or a history of regular (more than weekly) use of tobacco- or nicotine-containing products within two months prior to screening History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last three months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1-Experimental<br>4 healthy adult participants will be randomized to receive 1% icotinib hydrochloride cream, applied twice daily for 7 consecutive days (final dose on the morning of Day 8). The drug will be used topically to the back of each participant within an area of 15cm x 25cm. | Drug: 1% icotinib hydrochloride cream<br>* Topical administration for twice daily<br>* Other names: no other name;|
| Placebo Comparator: Cohort 1-Placebo<br>2 healthy adult participants will be randomized to receive placebo (blank cream), applied twice daily for 7 consecutive days (final dose on the morning of Day 8). The drug will be used topically to the back of each participant within an area of 15cm x 25cm. | Drug: Placebo<br>* Topical administration for twice daily.<br>* Other names: Blank Cream;|
| Experimental: Cohort 2-Experimental<br>4 healthy adult participants will be randomized to receive 2% icotinib hydrochloride cream, applied twice daily for 7 consecutive days (final dose on the morning of Day 8). The drug will be used topically to the back of each participant within an area of 15cm x 25cm. | Drug: 2% icotinib hydrochloride cream<br>* Topical administration for twice daily.<br>* Other names: no other name;|
| Placebo Comparator: Cohort 2-Placebo<br>2 healthy adult participants will be randomized to receive matching placebo, applied twice daily for 7 consecutive days (final dose on the morning of Day 8). The drug will be used topically to the back of each participant within an area of 15cm x 25cm. | Drug: Placebo<br>* Topical administration for twice daily.<br>* Other names: Blank Cream;|
| Experimental: Cohort 3-Experimental<br>6 patients with mild to moderate psoriasis will be randomized to receive 1% icotinib hydrochloride cream, applied twice daily for 13 consecutive days (final dose on the morning of Day 14). The drug will be applied topically to the psoriasis site (excluding face, scalp, genital and groin) on the arms and/or legs and/or trunk only. | Drug: 1% icotinib hydrochloride cream<br>* Topical administration for twice daily<br>* Other names: no other name;|
| Placebo Comparator: Cohort 3-Placebo<br>2 patients with mild to moderate psoriasis will be randomized to receive matching placebo, applied twice daily for 13 consecutive days (final dose on the morning of Day 14). The drug will be applied topically to the psoriasis site (excluding face, scalp, genital and groin) on the arms and/or legs and/or trunk only. | Drug: Placebo<br>* Topical administration for twice daily.<br>* Other names: Blank Cream;|
| Experimental: Cohort 4-Experimental<br>6 patients with mild to moderate psoriasis will be randomized to receive 2% icotinib hydrochloride cream, applied twice daily for 13 consecutive days (final dose on the morning of Day 14). The drug will be applied topically to the psoriasis site (excluding face, scalp, genital and groin) on the arms and/or legs and/or trunk only. | Drug: 2% icotinib hydrochloride cream<br>* Topical administration for twice daily.<br>* Other names: no other name;|
| Placebo Comparator: Cohort 4-Placebo<br>2 patients with mild to moderate psoriasis will be randomized to receive matching placebo, applied twice daily for 13 consecutive days (final dose on the morning of Day 14). The drug will be applied topically to the psoriasis site (excluding face, scalp, genital and groin) on the arms and/or legs and/or trunk only. | Drug: Placebo<br>* Topical administration for twice daily.<br>* Other names: Blank Cream;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events in healthy subjects | Incidence and severity of Adverse Events (AE) Vital signs (temperature, Heart Rate (HR), BP and respiration); Clinical laboratory assessments (serum chemistry, hematology and urinalysis); ECG; Use of concomitant medications | 8 days | 
| Adverse events in patients with mild to moderate psoriasis | Incidence and severity of AEs; Vital signs (temperature, HR, BP and respiration); Clinical laboratory assessments (serum chemistry, hematology and urinalysis); ECG; Use of concomitant medications | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance-related skin reactions in healthy adult participants at the tested sites | Skin irritation and allergy observation (including redness, swelling, itching, pain) | 8 days | 
| Tolerance-related skin reactions in patients with mild to moderate psoriasis at the tested sites | Skin irritation and allergy observation (including redness, swelling, itching, pain) | 14 days | 
| To investigate peak plasma concentration (Cmax) of single-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 8 days | 
| To investigate time maximum concentration observed(tmax) of single-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 8 days | 
| To investigate area under the plasma concentration versus time curve(AUC) of single-dose Icotinib Hydrochloride Cream in healthy adult participants | AUClast, AUC0-inf will be assessed | 8 days | 
| To investigate half life(t1/2) of single-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 8 days | 
| To investigate stable peak plasma concentration (Cmaxss) of repeat-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 8 days | 
| To investigate time maximum concentration observed(tmax) of repeat-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 8 days | 
| To investigate area under the plasma concentration versus time curve(AUC) of repeat-dose Icotinib Hydrochloride Cream in healthy adult participants | AUC0-12,AUClast, AUC0-inf will be assessed | 8 days | 
| To investigate half life(t1/2) of repeat-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 8 days | 
| To investigate peak plasma concentration (Cmax) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis |  | 14 days | 
| To investigate time maximum concentration observed(tmax) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis |  | 14 days | 
| To investigate area under the plasma concentration versus time curve(AUC) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis | AUClast, AUC0-inf will be assessed | 14 days | 
| To investigate half life(t1/2) of single-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis |  | 14 days | 
| To investigate stable peak plasma concentration (Cmaxss) of repeat-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis |  | 14 days | 
| To investigate time maximum concentration observed(tmax) of repeat-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis |  | 14 days | 
| To investigate area under the plasma concentration versus time curve(AUC) of repeat-dose Icotinib Hydrochloride Cream in patients with mild to moderate psoriasis | AUC0-12,AUClast, AUC0-inf will be assessed | 14 days | 
| To investigate half life(t1/2) of repeat-dose Icotinib Hydrochloride Cream in healthy adult participants |  | 14 days | 
| Psoriasis Area and Severity Index (PASI) Scores in patients with mild to moderate psoriasis |  | 14 days | 
| Dose-toxicity correlation in single-dose and repeat-dose administration | If observable trends exist between dose applied (in Part 2 of the study) and toxicity and response parameters. | 14 days | 
| Dermatology Life Quality Index (DLQI) |  | 14 days | 
| Dose-response correlation in single-dose and repeat-dose administration |  | 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EGFR inhibitor, topical agent, psoriasis, phase 1