A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of LFX453

Study Overview
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Brief Summary
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The purpose of this first-in human study is to demonstrate systemic and local tolerability and investigate pharmacokinetics of LFX453 after multiple topical applications in healthy subjects. The current study has been designed with three distinct parts. Part 1 focuses on safety and tolerability of once daily application on the back, prior to moving forward and assessing the safety and tolerability in more sensitive treatment areas in Part 2 or twice daily application in Part 3.

Official Title
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A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of LFX453, After Multiple Topical Applications in Healthy Volunteers.

Conditions
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Healthy

Intervention / Treatment
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* Drug: LFX453 H1
* Drug: LFX453 L1
* Drug: LFX453 H2
* Drug: LFX453 L2
* Drug: Imiquimod
* Drug: Placebo 1
* Drug: Placebo 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects of non-childbearing potential, 18 to 65 years of age inclusive (at the time of the screening visit), and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. Male subjects must agree to total abstinence from male:female intercourse or agree to use a condom during drug dosing and for four weeks after dosing has stopped. Exclusion Criteria: History of serious allergic reaction to any drug. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. History of any atopic dermatitis (only within the last 2 years), autoimmune disease, psoriasis or erythema multiforme. Presence of skin disease (e.g. warts) or skin features on treatment areas that may affect local tolerability or the ability of the investigator to evaluate local tolerability. History of heart failure, left ventricular dysfunction or known family history or known presence of long QT syndrome. A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline: 2nd or 3rd degree AV-block PR > 200 msec QRS complex > 120 msec QTcF > 450 msec (males) QTcF > 460 msec (females) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: LFX453/placebo<br>once daily: LFX453 cream 1 high dose / LFX453 cream 1 low dose /Placebo 1 / LFX453 cream 2 high dose / LFX453 cream 2 low dose / Placebo 2 | Drug: LFX453 H1<br>* LFX453 high dose cream 1<br>Drug: LFX453 L1<br>* LFX453 low dose cream 1<br>Drug: LFX453 H2<br>* LFX453 high dose cream 2<br>Drug: LFX453 L2<br>* LFX453 low dose cream 2<br>Drug: Placebo 1<br>* Placebo cream 1<br>Drug: Placebo 2<br>* Placebo cream 2<br>|
| Experimental: Part 2 groupA: LFX453/placebo<br>once daily: LFX453 cream 1 / Placebo 1 | Drug: LFX453 H1<br>* LFX453 high dose cream 1<br>Drug: LFX453 L1<br>* LFX453 low dose cream 1<br>Drug: LFX453 H2<br>* LFX453 high dose cream 2<br>Drug: LFX453 L2<br>* LFX453 low dose cream 2<br>Drug: Placebo 1<br>* Placebo cream 1<br>Drug: Placebo 2<br>* Placebo cream 2<br>|
| Experimental: Part 2 groupB: LFX453/placebo<br>once daily: LFX453 cream 2 / Placebo 2 | Drug: LFX453 H1<br>* LFX453 high dose cream 1<br>Drug: LFX453 L1<br>* LFX453 low dose cream 1<br>Drug: LFX453 H2<br>* LFX453 high dose cream 2<br>Drug: LFX453 L2<br>* LFX453 low dose cream 2<br>Drug: Placebo 1<br>* Placebo cream 1<br>Drug: Placebo 2<br>* Placebo cream 2<br>|
| Experimental: Part 2 groupC: LFX453/LFX453<br>once daily: LFX453 cream 1 / LFX453 cream 2 | Drug: LFX453 H1<br>* LFX453 high dose cream 1<br>Drug: LFX453 L1<br>* LFX453 low dose cream 1<br>Drug: LFX453 H2<br>* LFX453 high dose cream 2<br>Drug: LFX453 L2<br>* LFX453 low dose cream 2<br>|
| Other: Part 2 groupD: Imiquimod<br>once daily: imiquimod cream | Drug: Imiquimod<br>* Imiquimod cream<br>|
| Experimental: Part 3: LFX453/placebo<br>twice daily: LFX453 cream 1 high dose / LFX453 cream 1 low dose /Placebo 1 / LFX453 cream 2 high dose / LFX453 cream 2 low dose / Placebo 2 | Drug: LFX453 H1<br>* LFX453 high dose cream 1<br>Drug: LFX453 L1<br>* LFX453 low dose cream 1<br>Drug: LFX453 H2<br>* LFX453 high dose cream 2<br>Drug: LFX453 L2<br>* LFX453 low dose cream 2<br>Drug: Placebo 1<br>* Placebo cream 1<br>Drug: Placebo 2<br>* Placebo cream 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General safety (number of subjects with adverse events) | Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events and death. | 14 days | 
| Local skin tolerability (tolerability score) | Summarized statistics on 5-point scale tolerability scores over 14 days of treatment. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All parts: Amount (ng/mL) of LFX453 in plasma | Evaluate systemic steady state pharmacokinetics in human after topical administration of LFX453. | 14 days | 
| Part 1 and 2: LFX453 concentrations (ng/g) in the skin | LFX453 analyzed in skin. | Day 14 and between days 18-21 | 
| All parts: LFX453 concentration (ng/mL) in urine | LFX453 analyzed in urine. | Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteer