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

NCT02052687 | Completed Phase 1

• 2 other identifiers: CLFX453X21012013-002344-84
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy volunteer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• All parts: Amount (ng/mL) of LFX453 in plasma

  14 days

• Part 1 and 2: LFX453 concentrations (ng/g) in the skin

  Day 14 and between days 18-21

• All parts: LFX453 concentration (ng/mL) in urine

  Day 14

Study Arms (6)

Part 1: LFX453/placebo

EXPERIMENTAL

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; Drug: LFX453 L1; Drug: LFX453 H2; Drug: LFX453 L2; Drug: Placebo 1; Drug: Placebo 2

Part 2 groupA: LFX453/placebo

EXPERIMENTAL

once daily: LFX453 cream 1 / Placebo 1

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

Part 2 groupB: LFX453/placebo

EXPERIMENTAL

once daily: LFX453 cream 2 / Placebo 2

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

Part 2 groupC: LFX453/LFX453

EXPERIMENTAL

once daily: LFX453 cream 1 / LFX453 cream 2

Drug: LFX453 H1; Drug: LFX453 L1; Drug: LFX453 H2; Drug: LFX453 L2

Part 2 groupD: Imiquimod

OTHER

once daily: imiquimod cream

Drug: Imiquimod

Part 3: LFX453/placebo

EXPERIMENTAL

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; Drug: LFX453 L1; Drug: LFX453 H2; Drug: LFX453 L2; Drug: Placebo 1; Drug: Placebo 2

Interventions

LFX453 H1 DRUG

LFX453 high dose cream 1

Part 1: LFX453/placebo; Part 2 groupA: LFX453/placebo; Part 2 groupB: LFX453/placebo; Part 2 groupC: LFX453/LFX453; Part 3: LFX453/placebo

LFX453 L1 DRUG

LFX453 low dose cream 1

Part 1: LFX453/placebo; Part 2 groupA: LFX453/placebo; Part 2 groupB: LFX453/placebo; Part 2 groupC: LFX453/LFX453; Part 3: LFX453/placebo

LFX453 H2 DRUG

LFX453 high dose cream 2

Part 1: LFX453/placebo; Part 2 groupA: LFX453/placebo; Part 2 groupB: LFX453/placebo; Part 2 groupC: LFX453/LFX453; Part 3: LFX453/placebo

LFX453 L2 DRUG

LFX453 low dose cream 2

Part 1: LFX453/placebo; Part 2 groupA: LFX453/placebo; Part 2 groupB: LFX453/placebo; Part 2 groupC: LFX453/LFX453; Part 3: LFX453/placebo

Imiquimod DRUG

Imiquimod cream

Part 2 groupD: Imiquimod

Placebo 1 DRUG

Placebo cream 1

Part 1: LFX453/placebo; Part 2 groupA: LFX453/placebo; Part 2 groupB: LFX453/placebo; Part 3: LFX453/placebo

Placebo 2 DRUG

Placebo cream 2

Part 1: LFX453/placebo; Part 2 groupA: LFX453/placebo; Part 2 groupB: LFX453/placebo; Part 3: LFX453/placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• nd 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Mid Glamorgan, CF484DR, United Kingdom

Location

MeSH Terms

Interventions

Imiquimod

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: February 3, 2014
• Study Start: January 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: May 15, 2015

Record last verified: 2015-05

Locations

GB (1)