Icotinib Hydrochloride Cream in Healthy Adults and Psoriasis Patients

Phase 1

Completed

• Conditions: Psoriasis
• Interventions: Drug: Placebo; Drug: 2% icotinib hydrochloride cream; Drug: 1% icotinib hydrochloride cream

• Registration Number: NCT02574091
• Lead Sponsor: Betta Pharmaceuticals Co., Ltd.

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).

Study Timeline

• Study First Submitted: 2015-09-28
• Study First Submitted QC: 2015-10-08
• Study First Posted: 2015-10-12
• Study Start: 2015-11-26
• Primary Completion: 2017-02-19
• Study Completion: 2017-02-19
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-12
• Last Update Posted: 2017-07-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1-Placebo	Placebo	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.
Cohort 2-Experimental	2% icotinib hydrochloride cream	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.
Cohort 2-Placebo	Placebo	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.
Cohort 1-Experimental	1% icotinib hydrochloride cream	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.
Cohort 3-Experimental	1% icotinib hydrochloride cream	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.
Cohort 3-Placebo	Placebo	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.
Cohort 4-Experimental	2% icotinib hydrochloride cream	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.
Cohort 4-Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Adverse events in healthy subjects	8 days	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
Adverse events in patients with mild to moderate psoriasis	14 days	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Christchurch Clinical Studies Trust; 🇳🇿 Christchurch, New Zealand