First-in-Human Study of LHA510 in Elderly Subjects and Patients With Age-Related Macular Degeneration

NCT ID: NCT02076919

Last Updated: 2016-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2014-06-30

Brief Summary

The purpose of this first-in-human study is to assess the local ocular and systemic safety and tolerability of LHA510 eye drops when administered at various concentrations and dosing frequencies.

Detailed Description

This first-in-human study was conducted in two parts. Part 1 was a single ascending dose (SAD) design to assess the local ocular and systemic safety and tolerability of a single topical eye drop of LHA510 administered at various concentrations. Four separate cohorts of unique elderly subjects (55 to 80 years) were utilized, with each cohort randomized to receive either topical LHA510 or vehicle in a 3:1 ratio as a single dose. A disposition evaluation was performed 7 days later. Part 2 was a multiple ascending dose (MAD) design to assess the local ocular and systemic safety and tolerability of LHA510 administered at various concentrations and dosing frequencies. Six separate cohorts of unique AMD subjects were utilized, with each cohort randomized to receive either topical LHA510 or vehicle in a 3:1 ratio for 7 days. A disposition evaluation was performed 14 days after the first dose of study drug. A review of all available safety data was conducted by the Sponsor and the PI(s) prior to dose escalation (cohort progression). The same concentrations levels were used in Part 1 and Part 2 and are ordered as Lowest, Next Lowest, Next Highest, and Highest.

Conditions

Age-Related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

LHA510 Part 1

LHA510 Ophthalmic Suspension in 1 of 4 concentrations, 1 drop instilled in the study eye as a single dose during Part 1

Group Type: EXPERIMENTAL

LHA510 Ophthalmic Suspension

Intervention Type: DRUG

Ophthalmic suspension in 4 concentration levels topically administered in Part 1 and Part 2

LHA510 Vehicle Part 1

Inactive ingredients, 1 drop instilled in the study eye as a single dose during Part 1

Group Type: PLACEBO_COMPARATOR

LHA510 Vehicle

Intervention Type: DRUG

Inactive ingredients used for masking purposes

LHA510 Part 2

LHA510 Ophthalmic Suspension in 1 of 4 concentrations, 1 drop instilled in the study eye once, twice, or three times daily for 7 days during Part 2

Group Type: EXPERIMENTAL

LHA510 Ophthalmic Suspension

Intervention Type: DRUG

Ophthalmic suspension in 4 concentration levels topically administered in Part 1 and Part 2

LHA510 Vehicle Part 2

Inactive ingredients, 1 drop instilled in the study eye once, twice, or 3 times daily for 7 days during Part 2

Group Type: PLACEBO_COMPARATOR

LHA510 Vehicle

Intervention Type: DRUG

Inactive ingredients used for masking purposes

Interventions

LHA510 Ophthalmic Suspension

Ophthalmic suspension in 4 concentration levels topically administered in Part 1 and Part 2

Intervention Type: DRUG

LHA510 Vehicle

Inactive ingredients used for masking purposes

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provide written informed consent.
• Vital signs within the following ranges:

• oral body temperature between 35.0-37.5 °C
• systolic blood pressure, 90-150 mm Hg
• diastolic blood pressure, 50-90 mm Hg
• pulse rate, 40 - 100 bpm.
• Weigh at least 50 kg.
• Able to communicate well with the investigator.
• Able to understand and comply with the requirements of the study.

Additional eligibility criteria for Part 2 (AMD subjects):

• Evidence of AMD in one or both eyes.
• Age 55-90.

Exclusion Criteria

• Any currently active ocular condition that requires use of topical eye drops.
• Use of contact lens over the course of the study.
• Abnormal corneal examination results at screening or eligibility.
• History of any ocular surgery within the past 6 months prior to study participation.
• Use of other investigational drugs within 30 days of enrollment.
• History of hypersensitivity or allergy to any of the study drugs (including fluorescein) or to drugs of similar chemical classes.
• History of clinically significant ECG abnormalities, or any ECG abnormality at screening or eligibility.
• Known history or current clinically significant arrhythmias.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential.
• Use of any prohibited medication as specified in the protocol.
• Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing.
• Low hemoglobin levels at screening or eligibility as specified in the protocol.
• Significant illness as specified in the protocol.
• History of drug or alcohol abuse within the 12 months prior to dosing.

• Abnormal thickness of the central retinal subfield on OCT at screening.
• History of any chronic eye disease other than refractive error, incipient cataract, strabismic amblyopia, or anisometropic amblyopia.

• Any of the following treatments to the study eye within 28 days prior to dosing: ranibizumab (Lucentis®), aflibercept (Eylea®), bevacizumab (Avastin®), pegaptanib (Macugen®), or any other VEGF inhibitor.
• Patients who have required and received regular monthly injections of these drugs in the months preceding the study.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alcon Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Maietta, BSc

Role: STUDY_DIRECTOR

Alcon Research

Other Identifiers

C-13-007

Identifier Type: -

Identifier Source: org_study_id