AzTrials
AzTrials

Age-Related Macular DegenerationPhase 1NCT02076919

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

A Phase 1 study testing LHA510 Ophthalmic Suspension in people with Age-Related Macular Degeneration, run by Alcon Research.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 55 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Age-Related Macular Degeneration
What is being tested?
LHA510 Ophthalmic Suspension
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
110 participants
Where
No sites listed yet
Study dates
Feb 2014to Jun 2014
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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.
  • Other protocol-defined inclusion criteria may apply.

Who cannot join

  • 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.
Show all 22Show fewer
  • 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.
  • Additional exclusion criteria for Part 1 (healthy subjects):
  • 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.
  • Additional exclusion criteria for Part 2 (AMD subjects):
  • 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.

About this study

Official title: A Randomized, Double-Masked, Vehicle-Controlled, First-in-Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Topically Delivered LHA510 in Elderly Subjects and Patients With Age-Related Macular Degeneration

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.

Read the 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.

Being tested
LHA510 Ophthalmic Suspension, LHA510 Vehicle
Keywords
LHA510, First in human, Safety, Tolerability, Pharmacokinetics, Elderly, Age-Related Macular Degeneration, AMD, Ocular, Eye drop
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LHA510 Ophthalmic SuspensionDrug

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

  • LHA510 VehicleDrug

    Inactive ingredients used for masking purposes

Study groups in NCT02076919
Study groupRoleWhat they receive
LHA510 Part 1ExperimentalLHA510 Ophthalmic Suspension in 1 of 4 concentrations, 1 drop instilled in the study eye as a single dose during Part 1
Receives: Drug: LHA510 Ophthalmic Suspension
LHA510 Vehicle Part 1Placebo comparatorInactive ingredients, 1 drop instilled in the study eye as a single dose during Part 1
Receives: Drug: LHA510 Vehicle
LHA510 Part 2ExperimentalLHA510 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
Receives: Drug: LHA510 Ophthalmic Suspension
LHA510 Vehicle Part 2Placebo comparatorInactive ingredients, 1 drop instilled in the study eye once, twice, or 3 times daily for 7 days during Part 2
Receives: Drug: LHA510 Vehicle

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1

    A serious adverse event (SAE) was defined as any event which is fatal or life-threatening, which requires or prolongs hospitalization, which is significantly or permanently disabling or incapacitating, which constitutes a congenital anomaly or a birth defect, or which is medically significant, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.

    Measured: From time of consent until 30 days after stopping the trial/study drug

  2. Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 2

    A serious adverse event (SAE) was defined as any event which is fatal or life-threatening, which requires or prolongs hospitalization, which is significantly or permanently disabling or incapacitating, which constitutes a congenital anomaly or a birth defect, or which is medically significant, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.

    Measured: From time of consent until 30 days after stopping the trial/study drug

  3. Number of Subjects Experiencing a Non-serious Adverse Event, Part I

    An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.

    Measured: From time of consent until 30 days after stopping the trial/study drug

  4. Number of Subjects Experiencing a Non-serious Adverse Event, Part 2

    An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.

    Measured: From time of consent until 30 days after stopping the trial/study drug

Secondary outcomes (10)
  1. The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration [Mass / Volume] (Cmax), Part 2

    Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method.Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.

    Measured: Up to Day 15

  2. The Time to Reach the Maximum Concentration After Drug Administration [Time] (Tmax), Part 2

    Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.

    Measured: Up to Day 15

  3. The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [Mass x Time/Volume] (AUClast), Part 2

    Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.

    Measured: Up to Day 15

  4. The Terminal Elimination Half-life [Time] (T1/2), Part 2

    Plasma concentrations were quantitated using a high performance liquid chromatography/tandem mass spectometry method. Timepoints of assessment for Arms 1-4 were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose; and Day 15: 0h. Timepoints of assessment for LHA Highest BID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h and 12h post-dose; and Day 15: 0h. Timepoints of assessment for LHA510 Highest TID were Days 1 and 7: 0h (pre-dose), 0.25h, 0.5h, 1h, 2h, 4h, 0h (pre-2nd dose), 0.5h, 2h, 0h (pre-3rd dose), 0.25h, 0.5h, 1h, 2h, 4h, 12h post-dose; and Day 15: 0h.

    Measured: Up to Day 15

  5. Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 1

    Diastolic blood pressure (pressure in the arteries when the heart rests between beats) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.

    Measured: Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose

  6. Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 1

    Systolic blood pressure (pressure when the heart is contracting) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.

    Measured: Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose

  7. Change From Baseline in Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 1

    Mean arterial blood pressure (average pressure in the arteries during one cardiac cycle) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.

    Measured: Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose

  8. Change From Baseline in Diastolic Blood Pressure at Each Post Dose Timepoint, Part 2

    Diastolic blood pressure (pressure in the arteries when the heart rests between beats) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.

    Measured: Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose

  9. Change From Baseline in Systolic Blood Pressure at Each Post Dose Timepoint, Part 2

    Systolic blood pressure (pressure when the heart is contracting) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.

    Measured: Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose

  10. Change From Mean Arterial Blood Pressure at Each Post Dose Timepoint, Part 2

    Mean arterial blood pressure (average pressure in the arteries during one cardiac cycle) was measured using an automated validated device, with an appropriately sized cuff, and assessed in the sitting position after the subject had rested for at least 3 minutes, and again (when required) after 3 minutes in the standing position.

    Measured: Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionJun 2014
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02076919
Sponsor's protocol ID
C-13-007
Status last verified
Mar 2016
First submitted
28 Feb 2014
Last updated
1 Apr 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LHA510 Ophthalmic Suspension in people with Age-Related Macular Degeneration, run by Alcon Research.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug, Part 1 (time frame: From time of consent until 30 days after stopping the trial/study drug). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2016.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in