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

Novartis

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: LFX453 H1; Drug: Placebo 2; Drug: LFX453 L1; Drug: Imiquimod; Drug: Placebo 1; Drug: LFX453 L2; Drug: LFX453 H2

Study type: Interventional

Funder types: Industry

Identifiers

NCT02052687

2013-002344-84 (EudraCT Number)

CLFX453X2101

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

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41 participants in 6 patient groups

Part 1: LFX453/placebo

Experimental group

Description:

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

Treatment:

Drug: LFX453 L1

Drug: Placebo 1

Drug: LFX453 H2

Drug: LFX453 L2

Drug: LFX453 H1

Drug: Placebo 2

Part 2 groupA: LFX453/placebo

Experimental group

Description:

once daily: LFX453 cream 1 / Placebo 1

Treatment:

Drug: LFX453 L1

Drug: Placebo 1

Drug: LFX453 H2

Drug: LFX453 L2

Drug: LFX453 H1

Drug: Placebo 2

Part 2 groupB: LFX453/placebo

Experimental group

Description:

once daily: LFX453 cream 2 / Placebo 2

Treatment:

Drug: LFX453 L1

Drug: Placebo 1

Drug: LFX453 H2

Drug: LFX453 L2

Drug: LFX453 H1

Drug: Placebo 2

Part 2 groupC: LFX453/LFX453

Experimental group

Description:

once daily: LFX453 cream 1 / LFX453 cream 2

Treatment:

Drug: LFX453 L1

Drug: LFX453 H2

Drug: LFX453 L2

Drug: LFX453 H1

Part 2 groupD: Imiquimod

Other group

Description:

once daily: imiquimod cream

Treatment:

Drug: Imiquimod

Part 3: LFX453/placebo

Experimental group

Description:

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

Treatment:

Drug: LFX453 L1

Drug: Placebo 1

Drug: LFX453 H2

Drug: LFX453 L2

Drug: LFX453 H1

Drug: Placebo 2