Phase 1/2 Study of AGN-241622 in Healthy Participants and Participants With Presbyopia

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AGN-241622 ophthalmic solution for the first time in human participants

Official Title
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A First-in-Human, Phase 1/2, Dose-ascending, Multicenter, Masked, Randomized, Vehicle-controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AGN-241622 in Healthy Participants and Participants With Presbyopia (Stage 1 and Stage 2) and Efficacy in Participants With Presbyopia (Stage 2)

Conditions
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Presbyopia

Intervention / Treatment
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* Drug: AGN-241622
* Drug: AGN-190584
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40 to 65 at the time of study participation. Be a nonsmoker and nonuser of nicotine-containing products within the previous 1 year. Be able and willing to follow study instructions and complete all required study visits in the opinion of the study doctor. Exclusion Criteria: History of alcohol or substance abuse within the 5 years prior to study participation. Enrollment in another investigational drug or device study within 30 days of study participation. Women who are pregnant, nursing, or planning a pregnancy during the study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AGN-190584<br>Administered as single drop in each eye | Drug: AGN-190584<br>* Topical eye drop<br>|
| Experimental: AGN-241622 Dose 3<br>Administered as single drop in one eye or a single drop in each eye | Drug: AGN-241622<br>* Topical eye drop<br>|
| Experimental: AGN-241622 Dose 2<br>Administered as single drop in one eye or a single drop in each eye | Drug: AGN-241622<br>* Topical eye drop<br>|
| Placebo Comparator: Placebo Dose<br>Administered as single drop in one eye or a single drop in each eye | Drug: Vehicle<br>* Topical eye drop<br>|
| Experimental: AGN-241622 Dose 1<br>Administered as single drop in one eye or a single drop in each eye | Drug: AGN-241622<br>* Topical eye drop<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1: Number of patients experiencing a treatment emergent adverse event after single administration of AGN-241622 | The number of patients who experience one or more TEAE during the treatment period | Up to 2 days | 
| Stage 2a: Number of patients experiencing a treatment emergent adverse event after repeat administration of AGN-241622 | The number of patients who experience one or more TEAE during the treatment period | 14 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 1 Plasma Pharmacokinetics: Terminal elimination half-life (T1/2) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Terminal elimination rate constant (λz) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Maximum plasma concentrations (Cmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Time of maximum plasma concentrations (Tmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Apparent total clearance of AGN-241622 from plasma (CL/F) | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Volume of distribution during the terminal elimination phase (Vz/F) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Area under the concentration-time curve from time 0 to time t (AUC0-t) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Plasma Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Tears Pharmacokinetics: Area under the concentration-time curve from time 0 to time t (AUC0-t) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Tears Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Tears Pharmacokinetics: Maximum plasma concentrations (Cmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Tears Pharmacokinetics: Time of maximum plasma concentrations (Tmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Tears Pharmacokinetics: Terminal elimination rate constant (λz) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1 Tears Pharmacokinetics: Terminal elimination half-life (T1/2) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants | Day 1 | 
| Stage 1: Pupil diameter measurement | To evaluate the target receptor engagement of AGN-241622 as compared with vehicle administered once, unilaterally in healthy participants | Day 1 | 
| Stage 2a Plasma Pharmacokinetics: Area under the concentration-time curve from time 0 to time t (AUC0-t) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Area under the plasma/tear concentration versus time curve from time 0 to the end of the dosing period (AUC0-tau) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Maximum plasma concentrations (Cmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Minimum plasma concentrations (Cmin) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Time of maximum plasma concentrations (Tmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Terminal elimination rate constant (λz) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Terminal elimination half-life (T1/2) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Apparent total clearance of AGN-241622 from plasma (CL/F) | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Volume of distribution during the terminal elimination phase (Vz/F) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Plasma Pharmacokinetics: Accumulation ratio of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Tears Pharmacokinetics: Area under the concentration-time curve from time 0 to time t (AUC0-t) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Tears Pharmacokinetics: Area under the plasma/tear concentration versus time curve from time 0 to the end of the dosing period (AUC0-tau) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Tears Pharmacokinetics: Maximum plasma concentrations (Cmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Tears Pharmacokinetics: Time of maximum plasma concentrations (Tmax) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Tears Pharmacokinetics: Terminal elimination rate constant (λz) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 
| Stage 2a Tears Pharmacokinetics: Terminal elimination half-life (T1/2) of AGN-241622 | To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia | 14 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Presbyopia,Healthy Subject,Subjects with Presbyopia