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

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)

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04403763

Enrollment

Registered

2020-05-27

Start date

2020-07-27

Completion date

2022-12-05

Last updated

2024-02-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Presbyopia

Keywords

Presbyopia,Healthy Subject,Subjects with Presbyopia

Brief summary

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

Interventions

DRUGAGN-241622

Topical eye drop

DRUGVehicle

Topical eye drop

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Up to 2 days	The number of participants who experience one or more TEAE during the treatment period
Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	14 Days	The number of patients who experience one or more TEAE during the treatment period

Secondary

Measure	Time frame	Description
Stage 1 Plasma Pharmacokinetics: Terminal Elimination Rate Constant (λz) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Plasma Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Plasma Pharmacokinetics: Time of Maximum Plasma Concentrations (Tmax) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Plasma Pharmacokinetics: Apparent Total Clearance of AGN-241622 From Plasma (CL/F)	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Plasma Pharmacokinetics: Volume of Distribution During the Terminal Elimination Phase (Vz/F) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Plasma Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to Time t (AUC0-t) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Plasma Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Tears Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Tears Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Tears Pharmacokinetics: Time of Maximum Plasma Concentrations (Tmax) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Tears Pharmacokinetics: Terminal Elimination Rate Constant (λz) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1 Tears Pharmacokinetics: Terminal Elimination Half-life (T1/2) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 1: Pupil Diameter Measurement	Day 1	To evaluate the target receptor engagement of AGN-241622 as compared with vehicle administered once, unilaterally in healthy participants
Stage 2a Plasma Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to Time t (AUC0-t) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 1 Tears Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to Time t (AUC0-t) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants
Stage 2a Plasma Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Minimum Plasma Concentrations (Cmin) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Time of Maximum Plasma Concentrations (Tmax) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Terminal Elimination Rate Constant (λz) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Terminal Elimination Half-life (T1/2) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Apparent Total Clearance of AGN-241622 From Plasma (CL/F)	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Volume of Distribution During the Terminal Elimination Phase (Vz/F) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Plasma Pharmacokinetics: Accumulation Ratio of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Tears Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to Time t (AUC0-t) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
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	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Tears Pharmacokinetics: Maximum Plasma Concentrations (Cmax) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Tears Pharmacokinetics: Time of Maximum Plasma Concentrations (Tmax) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Tears Pharmacokinetics: Terminal Elimination Rate Constant (λz) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 2a Tears Pharmacokinetics: Terminal Elimination Half-life (T1/2) of AGN-241622	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
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	14 Days	To evaluate the systemic and local pharmacokinetics of AGN-241622 after repeat bilateral administration in participants with presbyopia
Stage 1 Plasma Pharmacokinetics: Terminal Elimination Half-life (T1/2) of AGN-241622	Day 1	To evaluate the systemic and local pharmacokinetics of AGN-241622 administered once unilaterally in healthy participants

Countries

United States

Participant flow

Recruitment details

This study was to be conducted in 3 stages (Stage 1, Stage 2a, and Stage 2b) with participants being randomized to different stages with dose cohorts based on criteria. Due to Sponsor decision, the study was terminated before completion. This decision was not taken due to any safety reasons.

Participants by arm

Arm	Count
Placebo Dose Administered as single drop in one or both eyes Vehicle: Topical eye drop	19
Cohort 1: AGN-241622 Dose 1 (Low Dose) Administered as single drop in one eye AGN-241622: Topical eye drop	9
Cohort 2: AGN-241622 Dose 2 (Medium Dose) Administered as single drop in one eye AGN-241622: Topical eye drop	10
Cohort 3: AGN-241622 Dose 3 (High Dose) Administered as single drop in one eye AGN-241622: Topical eye drop	9
Cohort 4: AGN-241622 Dose 1 (Low Dose) Administered as a single drop in each eye AGN-241622: Topical eye drop	12
Cohort 5: AGN-241622 Dose 2 (Medium Dose) Administered as a single drop in each eye AGN-241622: Topical eye drop	11
Cohort 6: AGN-241622 Dose 3 (High Dose) Administered as a single drop in each eye AGN-241622: Topical eye drop	10
Total	80

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG006
Stage 1	Early termination due to PK tube failure	0	0	1	0
Stage 1	Participant did not dose due to Sponsor decision	1	1	0	0
Stage 2A	Adverse Event	0	0	0	1

Baseline characteristics

Characteristic	Placebo Dose	Cohort 1: AGN-241622 Dose 1 (Low Dose)	Cohort 2: AGN-241622 Dose 2 (Medium Dose)	Cohort 3: AGN-241622 Dose 3 (High Dose)	Cohort 4: AGN-241622 Dose 1 (Low Dose)	Cohort 5: AGN-241622 Dose 2 (Medium Dose)	Cohort 6: AGN-241622 Dose 3 (High Dose)	Total
Age, Customized <=50	8 Participants	6 Participants	2 Participants	2 Participants	2 Participants	6 Participants	1 Participants	27 Participants
Age, Customized >50	11 Participants	3 Participants	8 Participants	7 Participants	10 Participants	5 Participants	9 Participants	53 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	6 Participants	1 Participants	1 Participants	2 Participants	5 Participants	0 Participants	20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants	3 Participants	9 Participants	8 Participants	10 Participants	6 Participants	10 Participants	60 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	0 Participants	2 Participants	4 Participants	2 Participants	0 Participants	1 Participants	14 Participants
Race (NIH/OMB) Black or African American	4 Participants	1 Participants	2 Participants	0 Participants	4 Participants	1 Participants	4 Participants	16 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	10 Participants	8 Participants	6 Participants	5 Participants	6 Participants	10 Participants	5 Participants	50 Participants
Sex: Female, Male Female	14 Participants	6 Participants	8 Participants	3 Participants	7 Participants	9 Participants	5 Participants	52 Participants
Sex: Female, Male Male	5 Participants	3 Participants	2 Participants	6 Participants	5 Participants	2 Participants	5 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 8	0 / 9	0 / 9	0 / 9	0 / 12	0 / 11	0 / 10
other Total, other adverse events	3 / 9	7 / 8	4 / 9	0 / 9	1 / 9	0 / 12	3 / 11	2 / 10
serious Total, serious adverse events	0 / 9	0 / 8	0 / 9	0 / 9	0 / 9	0 / 12	0 / 11	0 / 10

Outcome results

Primary

Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622

The number of participants who experience one or more TEAE during the treatment period

Time frame: Up to 2 days

Population: The safety population consists of all participants who received at least 1 administration of study intervention. Participants will be summarized according to the study intervention they actually received.

Arm	Measure	Group	Value (NUMBER)
Stage 1 Placebo Dose	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Ocular	1 participants
Stage 1 Placebo Dose	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Non-ocular	2 participants
Cohort 1: AGN-241622 Dose 1 (Low Dose)	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Non-ocular	1 participants
Cohort 1: AGN-241622 Dose 1 (Low Dose)	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Ocular	7 participants
Cohort 2: AGN-241622 Dose 2 (Medium Dose)	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Ocular	1 participants
Cohort 2: AGN-241622 Dose 2 (Medium Dose)	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Non-ocular	3 participants
Cohort 3: AGN-241622 Dose 3 (High Dose)	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Ocular	0 participants
Cohort 3: AGN-241622 Dose 3 (High Dose)	Stage 1: Number of Participants Experiencing a Treatment Emergent Adverse Event After Single Administration of AGN-241622	Non-ocular	0 participants

Primary

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

Time frame: 14 Days

Arm	Measure	Group	Value (NUMBER)
Stage 1 Placebo Dose	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Ocular	1 participants
Stage 1 Placebo Dose	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Non-ocular	0 participants
Cohort 1: AGN-241622 Dose 1 (Low Dose)	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Non-ocular	0 participants
Cohort 1: AGN-241622 Dose 1 (Low Dose)	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Ocular	0 participants
Cohort 2: AGN-241622 Dose 2 (Medium Dose)	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Ocular	2 participants
Cohort 2: AGN-241622 Dose 2 (Medium Dose)	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Non-ocular	1 participants
Cohort 3: AGN-241622 Dose 3 (High Dose)	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Ocular	1 participants
Cohort 3: AGN-241622 Dose 3 (High Dose)	Stage 2a: Number of Patients Experiencing a Treatment Emergent Adverse Event After Repeat Administration of AGN-241622	Non-ocular	1 participants

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

Stage 1: Pupil Diameter Measurement

To evaluate the target receptor engagement of AGN-241622 as compared with vehicle administered once, unilaterally in healthy participants

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary

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

Time frame: Day 1

Secondary