Clinical trial NCT02052687: A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of LFX453
Official title: A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of LFX453, After Multiple Topical Applications in Healthy Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-02-03
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: General safety (number of subjects with adverse events)
timeFrame: 14 days
measure: Local skin tolerability (tolerability score)
timeFrame: 14 days
Secondary outcomes:
measure: All parts: Amount (ng/mL) of LFX453 in plasma
timeFrame: 14 days
measure: Part 1 and 2: LFX453 concentrations (ng/g) in the skin
timeFrame: Day 14 and between days 18-21
measure: All parts: LFX453 concentration (ng/mL) in urine
timeFrame: Day 14
Other outcomes:
Locations:
city: Mid Glamorgan
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: