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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LHA510 Part 1 | Experimental | LHA510 Ophthalmic Suspension in 1 of 4 concentrations, 1 drop instilled in the study eye as a single dose during Part 1 |
|
| LHA510 Vehicle Part 1 | Placebo Comparator | Inactive ingredients, 1 drop instilled in the study eye as a single dose during Part 1 |
|
| LHA510 Part 2 | Experimental | 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 |
|
| LHA510 Vehicle Part 2 | Placebo Comparator | Inactive ingredients, 1 drop instilled in the study eye once, twice, or 3 times daily for 7 days during Part 2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LHA510 Ophthalmic Suspension | Drug | Ophthalmic suspension in 4 concentration levels topically administered in Part 1 and Part 2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From time of consent until 30 days after stopping the trial/study drug |
| 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. | From time of consent until 30 days after stopping the trial/study drug |
| 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. | From time of consent until 30 days after stopping the trial/study drug |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Provide written informed consent.
Vital signs within the following ranges:
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):
Exclusion Criteria:
Additional exclusion criteria for Part 1 (healthy subjects):
Additional exclusion criteria for Part 2 (AMD subjects):
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| Name | Affiliation | Role |
|---|---|---|
| Robert Maietta, BSc | Alcon Research | Study Director |
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Of the 110 enrolled, 30 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (80).
Subjects were recruited from a single investigational site located in the US.
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| ID | Title | Description |
|---|---|---|
| FG000 | LHA510, Part 1 | Ophthalmic suspension in 1 of 4 concentrations, 1 drop instilled in the study eye as a single dose during Part 1 |
| FG001 | Vehicle, Part 1 | Inactive ingredients, 1 drop instilled in the study eye as a single dose during Part 1 |
| FG002 | LHA510, Part 2 | 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 |
| FG003 | Vehicle, Part 2 | Inactive ingredients, 1 drop instilled in the study eye once, twice, or 3 times daily for 7 days during Part 2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
This analysis population includes all enrolled subjects.
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| ID | Title | Description |
|---|---|---|
| BG000 | LHA510 Lowest, Part 1 | 1 drop instilled in the study eye as a single dose |
| BG001 | LHA510 Next Lowest, Part 1 | 1 drop instilled in the study eye as a single dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | This analysis population includes all enrolled subjects in Part 1. | Posted | Number | participants | From time of consent until 30 days after stopping the trial/study drug |
|
AEs were collected for the duration of the study (Feb 2014 - Jun 2014). This analysis group includes all enrolled subjects.
An AE is defined as any untoward medical occurrence in a patient who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained as solicited comments from the study subjects and observations by the study Investigator, as outlined in the study protocol.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LHA510 Lowest, Part 1 | 1 drop instilled in the study eye as a single dose |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Principal Clinical Scientist, CA CSI ID | Alcon Research, Ltd. | 1-888-451-3937 | alcon.medinfo@alcon.com |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| ID | Term |
|---|---|
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| C000628487 | acrizanib |
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| LHA510 Vehicle | Drug | Inactive ingredients used for masking purposes |
|
| From time of consent until 30 days after stopping the trial/study drug |
| Up to Day 15 |
| 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. | Up to Day 15 |
| 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. | Up to Day 15 |
| 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. | Up to Day 15 |
| 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. | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
| 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. | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
| 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. | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
| 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. | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
| 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. | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
| 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. | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
| BG002 | LHA510 Next Highest, Part 1 | 1 drop instilled in the study eye as a single dose |
| BG003 | LHA510 Highest, Part 1 | 1 drop instilled in the study eye as a single dose |
| BG004 | Vehicle, Part 1 | 1 drop instilled in the study eye as a single dose |
| BG005 | LHA510 Lowest, Part 2 | 1 drop instilled in the study eye once daily for 7 days |
| BG006 | LHA510 Next Lowest, Part 2 | 1 drop instilled in the study eye once daily for 7 days |
| BG007 | LHA510 Next Highest, Part 2 | 1 drop instilled in the study eye once daily for 7 days |
| BG008 | LHA510 Highest, Part 2 | 1 drop instilled in the study eye once daily for 7 days |
| BG009 | LHA510 Highest BID, Part 2 | 1 drop instilled in the study eye twice daily for 7 days |
| BG010 | LHA510 Highest TID, Part 2 | 1 drop instilled in the study eye three times daily for 7 days |
| BG011 | Vehicle, Part 2 | 1 drop instilled in the study eye once, twice, or three times daily for 7 days |
| BG012 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| LHA510 Next Lowest, Part 1 |
1 drop instilled in the study eye as a single dose |
| OG002 | LHA510 Next Highest, Part 1 | 1 drop instilled in the study eye as a single dose |
| OG003 | LHA510 Highest, Part 1 | 1 drop instilled in the study eye as a single dose |
| OG004 | Vehicle, Part 1 | 1 drop instilled in the study eye as a single dose |
|
|
| Primary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Number | participants | From time of consent until 30 days after stopping the trial/study drug |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Mean | Standard Deviation | ng/mL | Up to Day 15 |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Mean | Standard Deviation | hour | Up to Day 15 |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Mean | Standard Deviation | ng*h/mL | Up to Day 15 |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Mean | Standard Deviation | hour | Up to Day 15 |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 1. | Posted | Least Squares Mean | Standard Error | mmHg | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
|
|
|
| Primary | 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. | This analysis population includes all enrolled subjects in Part 1. | Posted | Number | participants | From time of consent until 30 days after stopping the trial/study drug |
|
|
|
| Primary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Number | participants | From time of consent until 30 days after stopping the trial/study drug |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 1. | Posted | Least Squares Mean | Standard Error | mmHg | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 1. | Posted | Least Squares Mean | Standard Error | mmHg | Day 1: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Least Squares Mean | Standard Error | mmHg | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Least Squares Mean | Standard Error | mmHg | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
|
|
|
| Secondary | 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. | This analysis population includes all enrolled subjects in Part 2. | Posted | Least Squares Mean | Standard Error | mmHg | Day 1 and 7: 0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h and 24h post-dose |
|
|
|
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | LHA510 Next Lowest, Part 1 | 1 drop instilled in the study eye as a single dose | 0 | 6 | 1 | 6 |
| EG002 | LHA510 Next Highest, Part 1 | 1 drop instilled in the study eye as a single dose | 0 | 6 | 0 | 6 |
| EG003 | LHA510 Highest, Part 1 | 1 drop instilled in the study eye as a single dose | 0 | 6 | 1 | 6 |
| EG004 | Vehicle, Part 1 | 1 drop instilled in the study eye as a single dose | 0 | 8 | 1 | 8 |
| EG005 | LHA510 Lowest, Part 2 | 1 drop instilled in the study eye once daily for 7 days | 0 | 6 | 3 | 6 |
| EG006 | LHA510 Next Lowest, Part 2 | 1 drop instilled in the study eye once daily for 7 days | 0 | 6 | 1 | 6 |
| EG007 | LHA510 Next Highest, Part 2 | 1 drop instilled in the study eye once daily for 7 days | 0 | 6 | 1 | 6 |
| EG008 | LHA510 Highest, Part 2 | 1 drop instilled in the study eye once daily for 7 days | 0 | 6 | 2 | 6 |
| EG009 | LHA510 Highest BID, Part 2 | 1 drop instilled in the study eye twice daily for 7 days | 0 | 6 | 2 | 6 |
| EG010 | LHA510 Highest TID, Part 2 | 1 drop instilled in the study eye three times daily for 7 days | 0 | 6 | 1 | 6 |
| EG011 | Vehicle, Part 2 | 1 drop instilled in the study eye once, twice, or three times daily for 7 days | 0 | 12 | 3 | 12 |
| Diarrhea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
|
| Eye Pain | Eye disorders | MedDRA (16.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
|
| Infusion Site Irritation | General disorders | MedDRA (16.0) | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Sinus Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
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| Thrombophlebitis Superficial | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
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| Dry Eye | Eye disorders | MedDRA (16.0) | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (16.0) | Systematic Assessment |
|
| Vessel Puncture Site Swelling | General disorders | MedDRA (16.0) | Systematic Assessment |
|
Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
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