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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LFX453 H1; Drug: LFX453 L1; Drug: LFX453 H2; Drug: LFX453 L2; Drug: Placebo 1; Drug: Placebo 2; Drug: Imiquimod

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Mid Glamorgan, United Kingdom, CF484DR
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 30, 2014
• First Posted (Estimate): February 3, 2014

Study Record Updates

• Last Update Posted (Estimate): May 15, 2015
• Last Update Submitted That Met QC Criteria: May 14, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Healthy volunteer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Imiquimod
• Other Study ID Numbers: CLFX453X2101; 2013-002344-84 (EudraCT Number)