Dry Eye Disease, Dry Eye Syndrome
Conditions
Brief summary
This was a 2-stage study in which Stage 1 evaluated the safety of AGN-242428 and AGN-231868, how well they are tolerated, and how they move through the body when administered. After the sponsor's determination of adequate safety and tolerability of the interventions in Stage 1, Stage 2 began. Stage 2 also evaluated the safety and tolerability of AGN-242428 and AGN-231868, how effective they are in treating dry eye disease (DED), and assessed the plasma and tear exposure of both ophthalmic solutions.
Detailed description
Participants with DED in Cohort 1A were randomized 3:3:1:1 to receive AGN-242428 (Low Dose), AGN-231868 (Low Dose), or their respective vehicles (4 treatment groups total) to the left eye on Day 1 (Visit 2). If there were no significant study drug-related safety findings, starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single dose administration to both eyes on Day 15 (Visit 5). Upon completion of Cohort 1A, an independent data monitoring committee reviewed the data before proceeding to the next cohort. Cohort 1B participants were randomized 3:3:1:1 to receive AGN-242428 (High Dose), AGN-231868 (High Dose), or their respective vehicles (4 treatment groups total) and followed the same dosing regimen used in Cohort 1A. All subjects enrolled in Stage 2 had DED. In addition, subjects were selected based on their response to a controlled adverse environment (CAE). Only subjects with DED who responded to the CAE exposure with an increase in the signs and symptoms of DED were enrolled in Stage 2. During Stage 2, participants were randomized in a 1:1:1:1:1 ratio (within each site), to receive AGN-242428 (High Dose), AGN-242428 vehicle, AGN-231868 (High Dose), AGN-231868 vehicle, or Lifitegrast Ophthalmic Solution (Xiidra). Participants administered the assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42.
Interventions
DRUGAGN-242428
Ophthalmic solution administered as a topical eye drop
DRUGAGN-231868
Ophthalmic solution administered as a topical eye drop
OTHERAGN-242428 Vehicle
Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
OTHERAGN-231868 Vehicle
Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
Ophthalmic solution administered as a topical eye drop
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Stage 1 & Stage 2: * Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study. * Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Stage 1: * Both of the following signs of DED in at least 1 eye at Screening and Baseline visits (the same eye does not need to qualify at both visits): * Total corneal fluorescein staining score ≥ 2 and ≤ 9 based on the NEI grading scale, with no score \> 2 in any 1 region; * Schirmer test with topical anesthesia score ≥ 1 and ≤ 10 mm/5 min. Stage 2: * ALL of the following in at least 1 eye at both the Screening and Baseline visits and the same eye must qualify at both Screening and Baseline visits: * Corneal fluorescein staining score ≥ 2 in at least 1 eye region and a total corneal fluorescein staining score of ≥ 4 and ≤ 12 based on NEI grading scale; * Schirmer test with topical anesthesia score ≥ 2 and ≤ 10 mm/5 min; * Mean TBUT of ≥ 2 and ≤ 10 seconds. Stage 1: \- Symptoms of DED at both the Screening and Baseline visits as defined by an OSDI total score of ≥ 13 with ≤ 3 responses of not applicable (NA). Stage 2: * Symptoms of DED at both the Screening and Baseline visits as defined by both: * OSDI score of ≥ 23 with ≤ 3 responses of not applicable (NA) in at least 1 eye; * Eye Dryness Score (assessed using the Visual Analog Scale \[VAS\] Symptom Items score ≥ 30).
Exclusion criteria
* Current diagnosis of glaucoma or ocular hypertension; evidence of glaucoma or mean intraocular pressure \> 21 mm Hg determined by Goldmann applanation tonometry, in either eye. * Diagnosis of recurrent, ongoing, or active ocular infection including, but not limited to herpes simplex or zoster, vaccinia, varicella, tuberculosis of the eye, acanthamoeba, or fungal disease. * Participation in a blood or plasma donation program within 60 or 30 days, respectively, prior to study intervention administration. * Positive test results for anti-HIV type 1 and 2, hepatitis B surface antigen, or anti-hepatitis C virus at the Screening visit. * Positive test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, or phencyclidine at the Screening or Baseline visits. * Positive pregnancy test at Screening or Baseline visits. * Currently breastfeeding or plans to breastfeed during the study. * History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or participant safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | Day 42 (Post-CAE) | Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Participants completed questionnaires after exposure to a controlled adverse environment (CAE) for approximately 90 minutes. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention. |
| Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline | Day 1 to Day 42 | Percentage of participants with a clinically significant finding postbaseline, post-CAE. A clinically significant finding is defined as more than one severity grade increase (worsening) from baseline or positive status change from absence at baseline to presence at postbaseline (not associated with a severity grade) in one or both eyes. |
| Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | Day 1 to Day 42 | The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported. |
| Stage 1: Number of Participants With Adverse Events | Day 1 to Day 15 | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. |
| Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the area under the plasma concentration versus time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the plasma concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose. |
| Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the area under the tear concentration versus (vs) time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the tear concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose. |
| Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the plasma Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Cmax (Visit 5) was calculated. |
| Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the tear Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Cmax (Visit 5) was calculated. |
| Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the plasma Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Tmax (Visit 5) was calculated. |
| Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the tear Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Tmax (Visit 5) was calculated. |
| Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration | Day 2 (Predose and up to 12 hours postdose). | Following single dose administration, the plasma T1/2 (Day 2; Visit 3) was calculated. |
| Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration | Day 15 (Predose and up to 12 hours postdose) | Following repeat dose administration twice daily for 14 days, plasma T1/2 (Day 15; Visit 5) was calculated. |
| Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Day 2 and Day 15 (Predose and up to 12 hours postdose) | Following single dose administration, the tear T1/2 (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, tear T1/2 (Visit 5) was calculated. |
| Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | Day 15 (Predose and up to 12 hours postdose) | Following repeat dose administration twice daily for 14 days, the tear Cmin,ss (Visit 5) was calculated. |
| Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | Day 15 (Predose and up to 12 hours postdose) | Following repeat dose administration twice daily for 14 days, the plasma Cmin,ss (Visit 5) was calculated. |
| Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Day 15 (up to 12 hours) / Day 1 (up to 12 hours) | Following repeat dose administration, the mean plasma and tear AI(area under curve \[AUC\]) was calculated. AI(AUC) is reported as the ratio of exposure (AUC) at steady state (Day 15) to the exposure after a single daily dose (Day 1). Values greater than one are indicative of drug accumulation with repeat dosing. |
| Stage 1: Mean Drop Tolerability Questionnaire Scores | Day 15 | Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention. |
| Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Day 1 to Day 15 | The percentage of participants with non-PCS baseline value and met PCS criterion at least once postbaseline for clinical laboratory values. |
| Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Day 1 to Day 15 | The percentage of participants who met PCS criteria at least once postbaseline for vital sign values (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature) |
| Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Day 1 to Day 15 | The percentage of participants with PCS postbaseline (but not at baseline) ECG values for QRS interval, PR interval, and QTc (Fridericia) |
| Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 1 to Day 15 | At least 2 measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated. |
| Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 1 to Day 15 | BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol. |
| Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Day 1 to Day 15 | The number of participants with any ophthalmoscopy findings of any severity increase from baseline at one or more visit. |
| Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | Day 1 to Day 15 | The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported. |
| Stage 2: Number of Participants With Adverse Events | Day 1 to Day 42 | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. |
| Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Day 42 | The percentage of participants who have PCS postbaseline clinical laboratory values at Day 42 (Visit 6). |
| Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Day 42 | The percentage of participants who met PCS criteria at least once postbaseline for vital sign values at Day 42 (Visit 6) (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator. |
| Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Day 42 | The percentage of participants who have PCS ECG at Visit 6 (but not baseline) pre and post-controlled adverse environment (CAE). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator. |
| Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 1, Day 42 | At least 2 IOP measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated. Average intraocular pressure = mean of the 2 (or 3) measures in the study eye and non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default. |
| Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 1, Day 42 | BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol in the study eye and the non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h) | Day 42 | Trough plasma concentration (Ctrough) and plasma concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks |
| Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | Day 42 | Trough tear concentration (Ctrough) and tear concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks |
Countries
United States
Participant flow
Recruitment details
In Stage 1, 48 participants at 2 sites in the US were randomized and treated (24 participants each in Cohorts 1A and 1B). In Stage 2, 244 subjects at 10 sites in the US were randomized and treated (49 subjects each in the AGN-242428 (High Dose), AGN-242428 vehicle, and AGN-231868 vehicle groups; 47 subjects in the AGN-231868 (High Dose); and 50 subjects in the Xiidra 5% group).
Pre-assignment details
All safety analyses were performed on the safety population, which included all randomized participants who received at least 1 administration of study intervention (Stage 1, n=48; Stage 2, n=244). The pharmacokinetic population (Stage 1) included all participants with evaluable PK parameters in Stage 1. The pharmacokinetic population (Stage 2) included all participants with available plasma or tear concentrations in Stage 2.
Participants by arm
| Arm | Count |
|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) Participants received AGN-242428 (Low dose) in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 9 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle Participants received Vehicle in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 3 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) Participants received AGN-231868 (Low dose) in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 9 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle Participants received Vehicle in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 3 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) Participants received AGN-242428 (High dose) in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 9 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle Participants received Vehicle in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 3 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) Participants received AGN-231868 (High dose) in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 9 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle Participants received Vehicle in the left eye on Day 1 (Visit 2). Starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single-dose administration to both eyes on Day 15 (Visit 5). | 3 |
| Stage 2 Cohort 2: AGN-242428 (High Dose) Participants administered an artificial tear product (REFRESH PLUS®) twice daily to both eyes for 2 weeks (run-in period). After the run-in period, participants received AGN-242428 (High dose). Participants administered assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42. | 49 |
| Stage 2 Cohort 2: AGN-242428 Vehicle Participants administered an artificial tear product (REFRESH PLUS®) twice daily to both eyes for 2 weeks (run-in period). After the run-in period, participants received Vehicle. Participants administered assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42. | 49 |
| Stage 2 Cohort 2: AGN-231868 (High Dose) Participants administered an artificial tear product (REFRESH PLUS®) twice daily to both eyes for 2 weeks (run-in period). After the run-in period, participants received AGN-231868 (High dose). Participants administered assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42. | 47 |
| Stage 2 Cohort 2: AGN-231868 Vehicle Participants administered an artificial tear product (REFRESH PLUS®) twice daily to both eyes for 2 weeks (run-in period). After the run-in period, participants received Vehicle. Participants administered assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42. | 49 |
| Stage 2 Cohort 2: Xiidra (Lifitegrast Ophthalmic Solution) Participants administered an artificial tear product (REFRESH PLUS®) twice daily to both eyes for 2 weeks (run-in period). After the run-in period, participants received Xiidra (lifitegrast ophthalmic solution). Participants administered Xiidra (lifitegrast ophthalmic solution) in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42. | 50 |
| Total | 292 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 |
| Stage 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Stage 2 | Technical Problems | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Stage 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 2 Cohort 2: AGN-242428 (High Dose) | Stage 2 Cohort 2: AGN-242428 Vehicle | Stage 2 Cohort 2: AGN-231868 (High Dose) | Stage 2 Cohort 2: AGN-231868 Vehicle | Stage 2 Cohort 2: Xiidra (Lifitegrast Ophthalmic Solution) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 10.82 | 71.7 years STANDARD_DEVIATION 8.02 | 65.0 years STANDARD_DEVIATION 8.47 | 65.3 years STANDARD_DEVIATION 3.79 | 60.0 years STANDARD_DEVIATION 7.94 | 71.0 years STANDARD_DEVIATION 6.56 | 68.7 years STANDARD_DEVIATION 8.5 | 68.7 years STANDARD_DEVIATION 7.23 | 60.7 years STANDARD_DEVIATION 14.75 | 64.0 years STANDARD_DEVIATION 11.84 | 65.2 years STANDARD_DEVIATION 13.92 | 63.1 years STANDARD_DEVIATION 12.43 | 63.3 years STANDARD_DEVIATION 13.74 | 63.6 years STANDARD_DEVIATION 12.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 3 Participants | 9 Participants | 3 Participants | 9 Participants | 3 Participants | 9 Participants | 3 Participants | 45 Participants | 48 Participants | 45 Participants | 48 Participants | 49 Participants | 282 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 7 Participants | 3 Participants | 6 Participants | 5 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants | 10 Participants | 6 Participants | 10 Participants | 12 Participants | 53 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 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 | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 2 Participants | 8 Participants | 2 Participants | 4 Participants | 3 Participants | 5 Participants | 1 Participants | 37 Participants | 31 Participants | 36 Participants | 33 Participants | 33 Participants | 204 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants | 1 Participants | 6 Participants | 2 Participants | 7 Participants | 3 Participants | 36 Participants | 37 Participants | 34 Participants | 30 Participants | 35 Participants | 205 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 13 Participants | 12 Participants | 13 Participants | 19 Participants | 15 Participants | 87 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 49 | 0 / 49 | 0 / 47 | 0 / 49 | 0 / 50 |
| other Total, other adverse events | 5 / 9 | 1 / 3 | 4 / 9 | 2 / 3 | 3 / 9 | 2 / 3 | 2 / 9 | 0 / 3 | 20 / 49 | 22 / 49 | 10 / 47 | 5 / 49 | 24 / 50 |
| serious Total, serious adverse events | 0 / 9 | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 9 | 0 / 3 | 0 / 49 | 0 / 49 | 1 / 47 | 2 / 49 | 0 / 50 |
Outcome results
Primary
Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration
Following single dose administration, the area under the plasma concentration versus time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the plasma concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | NA pg•hr/mL | — |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 805 pg•hr/mL | Standard Deviation 509 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 2740 pg•hr/mL | Standard Deviation 2180 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 3540 pg•hr/mL | Standard Deviation 2250 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 3790 pg•hr/mL | Standard Deviation 4410 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 1430 pg•hr/mL | Standard Deviation 1300 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 37800 pg•hr/mL | Standard Deviation 20900 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 32200 pg•hr/mL | Standard Deviation 26100 |
Primary
Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration
Following single dose administration, the area under the tear concentration versus (vs) time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the tear concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36). Data were not combined for both eyes from each subject but were calculated as separate 'N'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 14900 ng•hr/mL | Standard Deviation 39500 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 3720 ng•hr/mL | Standard Deviation 5570 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 4540 ng•hr/mL | Standard Deviation 5730 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 2530 ng•hr/mL | Standard Deviation 3060 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 7420 ng•hr/mL | Standard Deviation 6440 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 15100 ng•hr/mL | Standard Deviation 19500 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 45400 ng•hr/mL | Standard Deviation 72900 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 50900 ng•hr/mL | Standard Deviation 85500 |
Primary
Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline
The number of participants with any ophthalmoscopy findings of any severity increase from baseline at one or more visit.
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 7 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 5 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 4 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 3 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 2 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 3 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 3 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 5 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 6 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Right eye | 3 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline | Left eye | 3 Participants |
Primary
Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration
Following single dose administration, the plasma Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Cmax (Visit 5) was calculated.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 108 pg/mL | Standard Deviation 30 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | NA pg/mL | — |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 504 pg/mL | Standard Deviation 402 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 513 pg/mL | Standard Deviation 277 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 255 pg/mL | Standard Deviation 176 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 449 pg/mL | Standard Deviation 479 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 6460 pg/mL | Standard Deviation 2840 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 5790 pg/mL | Standard Deviation 4320 |
Primary
Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration
Following single dose administration, the tear Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Cmax (Visit 5) was calculated.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36). Data were not combined for both eyes from each subject but were calculated as separate 'N'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 1890 ng/mL | Standard Deviation 2780 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 5370 ng/mL | Standard Deviation 9550 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 1630 ng/mL | Standard Deviation 1780 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 2250 ng/mL | Standard Deviation 2940 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 6090 ng/mL | Standard Deviation 7120 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 3570 ng/mL | Standard Deviation 2810 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 17900 ng/mL | Standard Deviation 30400 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 17000 ng/mL | Standard Deviation 26300 |
Primary
Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration
Following repeat dose administration, the mean plasma and tear AI(area under curve \[AUC\]) was calculated. AI(AUC) is reported as the ratio of exposure (AUC) at steady state (Day 15) to the exposure after a single daily dose (Day 1). Values greater than one are indicative of drug accumulation with repeat dosing.
Time frame: Day 15 (up to 12 hours) / Day 1 (up to 12 hours)
Population: PK Population (Stage 1; N=36).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Plasma | NA ratio | — |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Tear | 3.53 ratio | Standard Deviation 3.97 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Tear | 5.04 ratio | Standard Deviation 8.36 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Plasma | 1.50 ratio | Standard Deviation 0.68 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Plasma | 2.94 ratio | Standard Deviation 1.83 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Tear | 2.13 ratio | Standard Deviation 2.15 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Plasma | 1.90 ratio | Standard Deviation 1.82 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration | Tear | 1.53 ratio | Standard Deviation 0.9 |
Primary
Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)
BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol.
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | 0.3 letters | Standard Deviation 0.87 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | -0.9 letters | Standard Deviation 2.1 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | 0.8 letters | Standard Deviation 4.71 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | -2.1 letters | Standard Deviation 3.55 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | -0.9 letters | Standard Deviation 2.47 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | 1.2 letters | Standard Deviation 4.18 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | 0.3 letters | Standard Deviation 1.15 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | 0.3 letters | Standard Deviation 1.53 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | 2.7 letters | Standard Deviation 5.69 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | 1.0 letters | Standard Deviation 3.61 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | 1.0 letters | Standard Deviation 4.58 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | 0.3 letters | Standard Deviation 0.58 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | -2.3 letters | Standard Deviation 3.39 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | -0.4 letters | Standard Deviation 1.74 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | 0.1 letters | Standard Deviation 3.22 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | -0.7 letters | Standard Deviation 2.4 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | -1.0 letters | Standard Deviation 3 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | -0.1 letters | Standard Deviation 1.96 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | -0.3 letters | Standard Deviation 3.21 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | -1.7 letters | Standard Deviation 2.31 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | -4.7 letters | Standard Deviation 3.79 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | -0.3 letters | Standard Deviation 2.08 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | -0.3 letters | Standard Deviation 0.58 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | -3.0 letters | Standard Deviation 1.73 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | 2.0 letters | Standard Deviation 2.35 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | -1.1 letters | Standard Deviation 2.26 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | 0.8 letters | Standard Deviation 2.11 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | -0.6 letters | Standard Deviation 2.83 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | 0.7 letters | Standard Deviation 2 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | 1.1 letters | Standard Deviation 3.52 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | 2.7 letters | Standard Deviation 3.51 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | -1.3 letters | Standard Deviation 2.52 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | 0.3 letters | Standard Deviation 0.58 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | 1.7 letters | Standard Deviation 3.79 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | 3.3 letters | Standard Deviation 3.21 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | -1.7 letters | Standard Deviation 1.53 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | -0.4 letters | Standard Deviation 1.13 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | 1.2 letters | Standard Deviation 1.92 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | 0.0 letters | Standard Deviation 2.29 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | 0.8 letters | Standard Deviation 1.79 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | 0.3 letters | Standard Deviation 2.24 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | 0.6 letters | Standard Deviation 2.07 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Left eye | 2.7 letters | Standard Deviation 4.04 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 8: Right eye | -1.0 letters | Standard Deviation 1 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Left eye | 1.7 letters | Standard Deviation 1.53 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 15: Right eye | -0.7 letters | Standard Deviation 1.15 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Right eye | -3.7 letters | Standard Deviation 3.06 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Day 2: Left eye | 1.3 letters | Standard Deviation 2.31 |
Primary
Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP)
At least 2 measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated.
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | 0.00 mmHg | Standard Deviation 2.062 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | 0.17 mmHg | Standard Deviation 2.291 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | -1.06 mmHg | Standard Deviation 1.782 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -1.44 mmHg | Standard Deviation 1.81 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | -1.75 mmHg | Standard Deviation 2.053 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -1.17 mmHg | Standard Deviation 1.62 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | -0.67 mmHg | Standard Deviation 1.528 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | 1.00 mmHg | Standard Deviation 2 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | 0.67 mmHg | Standard Deviation 1.528 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -0.67 mmHg | Standard Deviation 2.082 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | -1.33 mmHg | Standard Deviation 1.155 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -2.67 mmHg | Standard Deviation 3.055 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | -0.44 mmHg | Standard Deviation 3.005 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | 0.22 mmHg | Standard Deviation 3.27 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | 0.11 mmHg | Standard Deviation 2.804 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | 0.56 mmHg | Standard Deviation 2.92 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -1.11 mmHg | Standard Deviation 1.691 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -0.44 mmHg | Standard Deviation 1.59 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | -1.17 mmHg | Standard Deviation 2.021 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | -1.00 mmHg | Standard Deviation 2.646 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | 0.33 mmHg | Standard Deviation 2.309 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -0.33 mmHg | Standard Deviation 1.155 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | 0.33 mmHg | Standard Deviation 1.528 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -0.33 mmHg | Standard Deviation 2.082 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | 0.33 mmHg | Standard Deviation 2.236 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | -0.67 mmHg | Standard Deviation 2.905 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | 0.11 mmHg | Standard Deviation 2.837 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | 0.50 mmHg | Standard Deviation 2.872 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -1.00 mmHg | Standard Deviation 2.739 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -1.00 mmHg | Standard Deviation 3.527 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -3.33 mmHg | Standard Deviation 1.155 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | 0.17 mmHg | Standard Deviation 0.289 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | -0.17 mmHg | Standard Deviation 1.443 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -2.67 mmHg | Standard Deviation 1.155 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | -0.50 mmHg | Standard Deviation 0.5 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | 0.17 mmHg | Standard Deviation 2.021 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | -0.28 mmHg | Standard Deviation 2.123 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | 0.61 mmHg | Standard Deviation 2.607 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | 0.33 mmHg | Standard Deviation 2.107 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | -0.17 mmHg | Standard Deviation 2.385 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | -0.06 mmHg | Standard Deviation 2.157 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | 0.33 mmHg | Standard Deviation 3.132 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Left eye | 0.33 mmHg | Standard Deviation 1.528 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Right eye | -1.83 mmHg | Standard Deviation 2.021 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Left eye | 1.33 mmHg | Standard Deviation 0.764 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 8: Right eye | 1.17 mmHg | Standard Deviation 0.764 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 2: Left eye | -1.67 mmHg | Standard Deviation 1.155 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP) | Day 15: Right eye | 0.33 mmHg | Standard Deviation 1.155 |
Primary
Stage 1: Mean Drop Tolerability Questionnaire Scores
Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention.
Time frame: Day 15
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 68.0 score on a scale | Standard Deviation 16.73 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 67.4 score on a scale | Standard Deviation 11.19 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 68.6 score on a scale | Standard Deviation 22.04 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 71.6 score on a scale | Standard Deviation 9.62 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 72.4 score on a scale | Standard Deviation 14.65 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 60.8 score on a scale | Standard Deviation 21.31 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 71.8 score on a scale | Standard Deviation 11.76 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 77.8 score on a scale | Standard Deviation 7.69 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 69.0 score on a scale | Standard Deviation 46.77 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 68.7 score on a scale | Standard Deviation 46.48 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 76.0 score on a scale | Standard Deviation 33.81 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 67.7 score on a scale | Standard Deviation 45.65 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 71.7 score on a scale | Standard Deviation 42.16 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 68.0 score on a scale | Standard Deviation 41.87 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 70.0 score on a scale | Standard Deviation 38.43 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 89.3 score on a scale | Standard Deviation 11.59 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 76.9 score on a scale | Standard Deviation 29.68 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 88.6 score on a scale | Standard Deviation 10 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 73.1 score on a scale | Standard Deviation 29.16 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 74.1 score on a scale | Standard Deviation 30.06 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 81.3 score on a scale | Standard Deviation 27.73 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 86.3 score on a scale | Standard Deviation 14.04 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 79.1 score on a scale | Standard Deviation 28.16 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 89.8 score on a scale | Standard Deviation 9.93 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 71.7 score on a scale | Standard Deviation 14.57 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 84.0 score on a scale | Standard Deviation 17.09 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 84.0 score on a scale | Standard Deviation 5.2 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 86.7 score on a scale | Standard Deviation 12.5 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 89.3 score on a scale | Standard Deviation 7.37 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 87.7 score on a scale | Standard Deviation 10.79 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 83.0 score on a scale | Standard Deviation 14.8 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 71.3 score on a scale | Standard Deviation 17.79 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 56.3 score on a scale | Standard Deviation 27.78 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 57.6 score on a scale | Standard Deviation 23.5 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 57.0 score on a scale | Standard Deviation 23.26 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 57.6 score on a scale | Standard Deviation 20.88 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 46.8 score on a scale | Standard Deviation 20.5 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 70.8 score on a scale | Standard Deviation 17.71 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 64.1 score on a scale | Standard Deviation 19.12 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 59.0 score on a scale | Standard Deviation 22.78 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 72.3 score on a scale | Standard Deviation 23.46 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 76.0 score on a scale | Standard Deviation 12.77 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 55.0 score on a scale | Standard Deviation 32.19 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 67.3 score on a scale | Standard Deviation 30.44 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 76.3 score on a scale | Standard Deviation 22.81 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 63.3 score on a scale | Standard Deviation 14.22 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 76.7 score on a scale | Standard Deviation 13.58 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 69.3 score on a scale | Standard Deviation 11.93 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 77.2 score on a scale | Standard Deviation 21.29 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 77.9 score on a scale | Standard Deviation 16.87 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 70.8 score on a scale | Standard Deviation 25.99 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 74.0 score on a scale | Standard Deviation 22.87 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 67.3 score on a scale | Standard Deviation 21.67 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 76.4 score on a scale | Standard Deviation 13.24 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 61.2 score on a scale | Standard Deviation 24.42 |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 71.6 score on a scale | Standard Deviation 27.55 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much stickiness do you have with the study eye drops in your eyes? | 66.0 score on a scale | Standard Deviation 21.07 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How clear is your vision with the study eye drops in your eyes? | 56.0 score on a scale | Standard Deviation 21.93 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How soothing are the study eye drops in your eyes? | 58.7 score on a scale | Standard Deviation 19.86 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much discomfort do you have with the study eye drops in your eyes? | 73.3 score on a scale | Standard Deviation 14.01 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How moistening/lubricating are the study eye drops in your eyes? | 62.3 score on a scale | Standard Deviation 18.72 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much burning/stinging do you have with the study eye drops in your eyes? | 75.0 score on a scale | Standard Deviation 17.58 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How comfortable are the study eye drops in your eyes? | 62.0 score on a scale | Standard Deviation 11.14 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Mean Drop Tolerability Questionnaire Scores | How much blur do you have with the study eye drops in your eyes? | 61.7 score on a scale | Standard Deviation 25.58 |
Primary
Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration
Following repeat dose administration twice daily for 14 days, the plasma Cmin,ss (Visit 5) was calculated.
Time frame: Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 73.7 pg/mL | Standard Deviation 14.9 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 183 pg/mL | Standard Deviation 115 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 237 pg/mL | Standard Deviation 281 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 1650 pg/mL | Standard Deviation 1320 |
Primary
Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration
Following repeat dose administration twice daily for 14 days, the tear Cmin,ss (Visit 5) was calculated.
Time frame: Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36). Data were not combined for both eyes from each subject but were calculated as separate 'N'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 1050 ng/mL | Standard Deviation 3760 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 171 ng/mL | Standard Deviation 331 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 677 ng/mL | Standard Deviation 1710 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration | 897 ng/mL | Standard Deviation 1670 |
Primary
Stage 1: Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Time frame: Day 1 to Day 15
Population: Safety population (Stage 1; N=48)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Number of Participants With Adverse Events | 5 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Number of Participants With Adverse Events | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Number of Participants With Adverse Events | 4 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Number of Participants With Adverse Events | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Number of Participants With Adverse Events | 3 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Number of Participants With Adverse Events | 2 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Number of Participants With Adverse Events | 2 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Number of Participants With Adverse Events | 0 Participants |
Primary
Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values
The percentage of participants with PCS postbaseline (but not at baseline) ECG values for QRS interval, PR interval, and QTc (Fridericia)
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 1 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | QTc Fridericia (msec) actual value of > 500 or Increase of > 60 | 0 Participants |
Primary
Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)
The percentage of participants who met PCS criteria at least once postbaseline for vital sign values (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature)
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) Decrease of >=7% or Increase of >=7% | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Pulse Rate (beats/min) (<=50 and Decrease of >=15 or >=120 and Increase of >=15 | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (<35 or >38) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory Rate (breaths/min) (<=8 or >=28) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic Blood Pressure (mmHg) (<=90 and Decrease of >=20 or >=180 and Increase of >=20) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic Blood Pressure (mmHg) (<=50 and Decrease of >=15 or >=105 and Increase of >=15) | 0 Participants |
Primary
Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values
The percentage of participants with non-PCS baseline value and met PCS criterion at least once postbaseline for clinical laboratory values.
Time frame: Day 1 to Day 15
Population: Safety Population. Analysis included participants with a non-PCS baseline value and at least one post-baseline assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 2 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 3 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 1 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Leukocytes (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Erythrocytes (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (Ratio) (< 0.8 * lower limit of normal (LLN) or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose Fasting (mmol/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
Primary
Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination
The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 (High Dose) | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
Primary
Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration
Following repeat dose administration twice daily for 14 days, plasma T1/2 (Day 15; Visit 5) was calculated.
Time frame: Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36). Data was available for all participants; however, T1/2 was reported only when Rsq\_adjusted ≥ 0.8, per the planned analysis. Number Analyzed for each timepoint includes only those participants with Rsq\_adjusted ≥ 0.8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration | 16.2 hours | Standard Deviation 4.32 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration | 5.94 hours | Standard Deviation 1.72 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration | 11.5 hours | Standard Deviation 2.11 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration | 6.51 hours | Standard Deviation 4.43 |
Primary
Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration
Following single dose administration, the plasma T1/2 (Day 2; Visit 3) was calculated.
Time frame: Day 2 (Predose and up to 12 hours postdose).
Population: PK Population (Stage 1; N=36). Data was available for all participants; however, T1/2 was reported only when Rsq\_adjusted ≥ 0.8, per the planned analysis. Number Analyzed for each timepoint includes only those participants with Rsq\_adjusted ≥ 0.8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration | NA hours | — |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration | 4.98 hours | Standard Deviation 0.939 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration | 6.09 hours | Standard Deviation 2 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration | 3.60 hours | Standard Deviation 0.893 |
Primary
Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration
Following single dose administration, the tear T1/2 (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, tear T1/2 (Visit 5) was calculated.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36). Data were not combined for both eyes from each subject but were calculated as separate 'N'. Data was available for all participants; however, T1/2 was reported only when Rsq\_adjusted ≥ 0.8, per the planned analysis. Number Analyzed for each timepoint includes only those participants with Rsq\_adjusted ≥ 0.8.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 2.91 hours | Standard Deviation 1.29 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 6.65 hours | Standard Deviation 6.28 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 4.76 hours | Standard Deviation 4.02 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 3.24 hours | Standard Deviation 1.25 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 2.78 hours | Standard Deviation 1.48 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 2.47 hours | Standard Deviation 0.883 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 2.66 hours | Standard Deviation 1.61 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 2.59 hours | Standard Deviation 0.918 |
Primary
Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration
Following single dose administration, the plasma Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Tmax (Visit 5) was calculated.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 1.92 hours | Standard Deviation 0.939 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | NA hours | Standard Deviation 0.306 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 1.75 hours | Standard Deviation 0.415 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 0.983 hours | Standard Deviation 1.04 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 1.75 hours | Standard Deviation 1.17 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 1.78 hours | Standard Deviation 1.4 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Repeat Dose Administration: Day 15 (Visit 5) | 1.08 hours | Standard Deviation 0.499 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration | Plasma Single Dose Administration: Day 2 (Visit 3) | 1.75 hours | Standard Deviation 1.02 |
Primary
Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration
Following single dose administration, the tear Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Tmax (Visit 5) was calculated.
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
Population: PK Population (Stage 1; N=36). Data were not combined for both eyes from each subject but were calculated as separate 'N'.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 0.592 hours | Standard Deviation 0.869 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 0.575 hours | Standard Deviation 0.077 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 0.550 hours | Standard Deviation 0.444 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 0.600 hours | Standard Deviation 2.28 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 0.575 hours | Standard Deviation 0.46 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 0.700 hours | Standard Deviation 0.824 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Single Dose Administration: Day 2 (Visit 3) | 0.933 hours | Standard Deviation 1.95 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration | Tear Repeat Dose Administration: Day 15 (Visit 5) | 0.742 hours | Standard Deviation 1.88 |
Primary
Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment)
Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Participants completed questionnaires after exposure to a controlled adverse environment (CAE) for approximately 90 minutes. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention.
Time frame: Day 42 (Post-CAE)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How comfortable are the study eye drops in your eyes? | 50.9 score on a scale | Standard Deviation 32.71 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much burning/stinging do you have with the study eye drops in your eyes? | 47.9 score on a scale | Standard Deviation 36.42 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How clear is your vision with the study eye drops in your eyes? | 60.0 score on a scale | Standard Deviation 30.25 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much blur do you have with the study eye drops in your eyes? | 60.7 score on a scale | Standard Deviation 32.55 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much discomfort do you have with the study eye drops in your eyes? | 55.5 score on a scale | Standard Deviation 31.52 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How soothing are the study eye drops in your eyes? | 49.5 score on a scale | Standard Deviation 30.94 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How moistening/lubricating are the study eye drops in your eyes? | 58.2 score on a scale | Standard Deviation 28.5 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much stickiness do you have with the study eye drops in your eyes? | 75.8 score on a scale | Standard Deviation 24.52 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much discomfort do you have with the study eye drops in your eyes? | 60.6 score on a scale | Standard Deviation 30.35 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How comfortable are the study eye drops in your eyes? | 64.2 score on a scale | Standard Deviation 27.75 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How moistening/lubricating are the study eye drops in your eyes? | 67.3 score on a scale | Standard Deviation 21.25 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much stickiness do you have with the study eye drops in your eyes? | 68.2 score on a scale | Standard Deviation 27.37 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much blur do you have with the study eye drops in your eyes? | 58.4 score on a scale | Standard Deviation 29.91 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How clear is your vision with the study eye drops in your eyes? | 68.7 score on a scale | Standard Deviation 22.57 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How soothing are the study eye drops in your eyes? | 62.2 score on a scale | Standard Deviation 27.28 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much burning/stinging do you have with the study eye drops in your eyes? | 52.1 score on a scale | Standard Deviation 34.02 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How clear is your vision with the study eye drops in your eyes? | 66.0 score on a scale | Standard Deviation 23.24 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much stickiness do you have with the study eye drops in your eyes? | 62.5 score on a scale | Standard Deviation 30.42 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much discomfort do you have with the study eye drops in your eyes? | 61.8 score on a scale | Standard Deviation 30.78 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much burning/stinging do you have with the study eye drops in your eyes? | 54.5 score on a scale | Standard Deviation 32.2 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How soothing are the study eye drops in your eyes? | 67.4 score on a scale | Standard Deviation 24.99 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How moistening/lubricating are the study eye drops in your eyes? | 70.2 score on a scale | Standard Deviation 20.21 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much blur do you have with the study eye drops in your eyes? | 58.5 score on a scale | Standard Deviation 28.68 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How comfortable are the study eye drops in your eyes? | 69.3 score on a scale | Standard Deviation 24.12 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much burning/stinging do you have with the study eye drops in your eyes? | 69.3 score on a scale | Standard Deviation 32.19 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How clear is your vision with the study eye drops in your eyes? | 77.4 score on a scale | Standard Deviation 18.5 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much stickiness do you have with the study eye drops in your eyes? | 73.3 score on a scale | Standard Deviation 31.55 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much blur do you have with the study eye drops in your eyes? | 72.8 score on a scale | Standard Deviation 26.25 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much discomfort do you have with the study eye drops in your eyes? | 73.2 score on a scale | Standard Deviation 29.42 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How comfortable are the study eye drops in your eyes? | 82.9 score on a scale | Standard Deviation 16.68 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How soothing are the study eye drops in your eyes? | 80.1 score on a scale | Standard Deviation 18.78 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How moistening/lubricating are the study eye drops in your eyes? | 78.4 score on a scale | Standard Deviation 18.05 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much burning/stinging do you have with the study eye drops in your eyes? | 45.0 score on a scale | Standard Deviation 33.36 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much blur do you have with the study eye drops in your eyes? | 47.7 score on a scale | Standard Deviation 31.38 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much stickiness do you have with the study eye drops in your eyes? | 58.2 score on a scale | Standard Deviation 31.19 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How moistening/lubricating are the study eye drops in your eyes? | 61.8 score on a scale | Standard Deviation 27.39 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How soothing are the study eye drops in your eyes? | 55.1 score on a scale | Standard Deviation 30.36 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How much discomfort do you have with the study eye drops in your eyes? | 50.4 score on a scale | Standard Deviation 32.18 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How clear is your vision with the study eye drops in your eyes? | 51.6 score on a scale | Standard Deviation 30.86 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment) | How comfortable are the study eye drops in your eyes? | 58.5 score on a scale | Standard Deviation 28.18 |
Primary
Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)
BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol in the study eye and the non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default.
Time frame: Day 1, Day 42
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Study eye | 0.7 letters | Standard Deviation 3.96 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Non-study eye | -0.0 letters | Standard Deviation 4.02 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Study eye | 1.2 letters | Standard Deviation 4.16 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Non-study eye | 0.3 letters | Standard Deviation 3.35 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Study eye | 0.5 letters | Standard Deviation 4.13 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Non-study eye | 0.3 letters | Standard Deviation 6.26 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Non-study eye | 0.4 letters | Standard Deviation 3.68 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Study eye | 0.9 letters | Standard Deviation 2.8 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Study eye | 1.4 letters | Standard Deviation 4.11 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) | Non-study eye | 1.1 letters | Standard Deviation 4.23 |
Primary
Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP)
At least 2 IOP measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated. Average intraocular pressure = mean of the 2 (or 3) measures in the study eye and non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default.
Time frame: Day 1, Day 42
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Study eye | 0.7 mmHg | Standard Deviation 2.37 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Non-study eye | 0.9 mmHg | Standard Deviation 2.23 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Study eye | 0.2 mmHg | Standard Deviation 2.65 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Non-study eye | 0.3 mmHg | Standard Deviation 2.58 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Study eye | -0.5 mmHg | Standard Deviation 2.57 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Non-study eye | -0.6 mmHg | Standard Deviation 2.56 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Non-study eye | 0.5 mmHg | Standard Deviation 2.48 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Study eye | 0.2 mmHg | Standard Deviation 2.05 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Study eye | -0.1 mmHg | Standard Deviation 2.37 |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP) | Non-study eye | 0.3 mmHg | Standard Deviation 2.49 |
Primary
Stage 2: Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Time frame: Day 1 to Day 42
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Number of Participants With Adverse Events | 21 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Number of Participants With Adverse Events | 22 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Number of Participants With Adverse Events | 18 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Number of Participants With Adverse Events | 10 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Number of Participants With Adverse Events | 25 Participants |
Primary
Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values
The percentage of participants who have PCS ECG at Visit 6 (but not baseline) pre and post-controlled adverse environment (CAE). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.
Time frame: Day 42
Population: Safety Population. The Overall Number Analyzed for each arm refers to the overall number of participants with data available for the given assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QRS Interval (msec) actual value of >=150 | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: PR Interval (msec) actual value of >=250 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QRS Interval (msec) actual value of >=150 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QRS Interval (msec) actual value of >=150 | 3 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) actual value of > 500 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) Increase of > 60 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QRS Interval (msec) actual value of >=150 | 2 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QRS Interval (msec) actual value of >=150 | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) actual value of > 500 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QTc Fridericia (msec) Increase of > 60 | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: PR Interval (msec) actual value of >=250 | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Pre-CAE: QRS Interval (msec) actual value of >=150 | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values | Post-CAE: QTc Fridericia (msec) Increase of > 60 | 1 Participants |
Primary
Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)
The percentage of participants who met PCS criteria at least once postbaseline for vital sign values at Day 42 (Visit 6) (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.
Time frame: Day 42
Population: Safety Population. The Overall Number Analyzed for each arm refers to the overall number of participants with data available for the given assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) Low (Actual Value <= 50 and Change from baseline decrease of >= 15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (High [Actual Value >38] or Low [Actual Value <35]) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: Low (Actual Value <= 50 mmHg and Change from baseline Increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: Low (Actual Value <= 90 mmHg and Change from baseline decrease of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) (High [Change from baseline Increase >=7%] or Low (Change from baseline Decrease >=7%)] | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) High (Actual Value >=120 and Change from baseline increase >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: High (Actual Value >= 105 mmHg and Change from baseline increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory rate (BPM) (High [Actual Value >= 28] or Low [Actual Value <= 8]) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: High (Actual Value >= 180 mmHg and Change from baseline Increase of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: Low (Actual Value <= 90 mmHg and Change from baseline decrease of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: High (Actual Value >= 105 mmHg and Change from baseline increase of >= 15 mmHg) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (High [Actual Value >38] or Low [Actual Value <35]) | 2 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) High (Actual Value >=120 and Change from baseline increase >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) Low (Actual Value <= 50 and Change from baseline decrease of >= 15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: Low (Actual Value <= 50 mmHg and Change from baseline Increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) (High [Change from baseline Increase >=7%] or Low (Change from baseline Decrease >=7%)] | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: High (Actual Value >= 180 mmHg and Change from baseline Increase of >= 20 mmHg) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory rate (BPM) (High [Actual Value >= 28] or Low [Actual Value <= 8]) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: Low (Actual Value <= 50 mmHg and Change from baseline Increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) High (Actual Value >=120 and Change from baseline increase >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) Low (Actual Value <= 50 and Change from baseline decrease of >= 15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory rate (BPM) (High [Actual Value >= 28] or Low [Actual Value <= 8]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: High (Actual Value >= 105 mmHg and Change from baseline increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: Low (Actual Value <= 90 mmHg and Change from baseline decrease of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (High [Actual Value >38] or Low [Actual Value <35]) | 2 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: High (Actual Value >= 180 mmHg and Change from baseline Increase of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) (High [Change from baseline Increase >=7%] or Low (Change from baseline Decrease >=7%)] | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: High (Actual Value >= 180 mmHg and Change from baseline Increase of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory rate (BPM) (High [Actual Value >= 28] or Low [Actual Value <= 8]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: Low (Actual Value <= 50 mmHg and Change from baseline Increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) High (Actual Value >=120 and Change from baseline increase >=15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) Low (Actual Value <= 50 and Change from baseline decrease of >= 15) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (High [Actual Value >38] or Low [Actual Value <35]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) (High [Change from baseline Increase >=7%] or Low (Change from baseline Decrease >=7%)] | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: Low (Actual Value <= 90 mmHg and Change from baseline decrease of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: High (Actual Value >= 105 mmHg and Change from baseline increase of >= 15 mmHg) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Respiratory rate (BPM) (High [Actual Value >= 28] or Low [Actual Value <= 8]) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Temperature (C) (High [Actual Value >38] or Low [Actual Value <35]) | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: High (Actual Value >= 180 mmHg and Change from baseline Increase of >= 20 mmHg) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: High (Actual Value >= 105 mmHg and Change from baseline increase of >= 15 mmHg) | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Weight (kg) (High [Change from baseline Increase >=7%] or Low (Change from baseline Decrease >=7%)] | 3 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Diastolic: Low (Actual Value <= 50 mmHg and Change from baseline Increase of >= 15 mmHg) | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) Low (Actual Value <= 50 and Change from baseline decrease of >= 15) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Sitting Pulse Rate (BPM) High (Actual Value >=120 and Change from baseline increase >=15) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature) | Systolic: Low (Actual Value <= 90 mmHg and Change from baseline decrease of >= 20 mmHg) | 1 Participants |
Primary
Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination
The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.
Time frame: Day 1 to Day 42
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination | 0 Participants |
Primary
Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values
The percentage of participants who have PCS postbaseline clinical laboratory values at Day 42 (Visit 6).
Time frame: Day 42
Population: Safety Population. The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Blood Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (%) (Low: < 0.8 x LLN or High: >= 1.2 x ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (mmol/L) (< 0.8 * LLN or > 1.4 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | White blood cells (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Red blood cells (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Blood Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | White blood cells (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (mmol/L) (< 0.8 * LLN or > 1.4 * ULN) | 2 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 1 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 2 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Red blood cells (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (%) (Low: < 0.8 x LLN or High: >= 1.2 x ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (Urinalysis) (>= 2+) | 2 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (%) (Low: < 0.8 x LLN or High: >= 1.2 x ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Red blood cells (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Blood Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (mmol/L) (< 0.8 * LLN or > 1.4 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (Urinalysis) (>= 2+) | 2 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | White blood cells (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Blood Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (Urinalysis) (>= 2+) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Red blood cells (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (%) (Low: < 0.8 x LLN or High: >= 1.2 x ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 1 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | White blood cells (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (mmol/L) (< 0.8 * LLN or > 1.4 * ULN) | 0 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (mmol/L) (< 0.8 * LLN or > 1.4 * ULN) | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Bilirubin (umol/L) (> 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Potassium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Aspartate Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (g/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alkaline Phosphatase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Protein (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Sodium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Albumin (g/L) (< 0.9 * LLN or > 1.1 * ULN | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Eosinophils (10^9/L) (> 1.5 * upper limit of normal [ULN]) | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Glucose (Urinalysis) (>= 2+) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hemoglobin (g/L) (< 0.8 * LLN or >= 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | pH (Urinalysis) (< 0.9 * LLN or > 1.1 * ULN) | 1 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Alanine Aminotransferase (U/L) (> 3.0 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Hematocrit (%) (Low: < 0.8 x LLN or High: >= 1.2 x ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | White blood cells (10^9/L) (< 0.7 * LLN or > 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Specific Gravity (Urinalysis) (> 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Neutrophils (10^9/L) (< 0.6 * LLN or > 1.6 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Lymphocytes (10^9/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Red blood cells (10^12/L) (< 0.8 * LLN or > 1.2 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Platelets (10^9/L) (< 0.5 * LLN or > 1.5 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Cholesterol (mmol/L) (> 1.2 * ULN) | 2 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Creatinine (umol/L) (> 1.8 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Calcium (mmol/L) (< 0.9 * LLN or > 1.1 * ULN) | 0 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values | Blood Urea Nitrogen (mmol/L) (> 1.3 * ULN) | 0 Participants |
Primary
Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline
Percentage of participants with a clinically significant finding postbaseline, post-CAE. A clinically significant finding is defined as more than one severity grade increase (worsening) from baseline or positive status change from absence at baseline to presence at postbaseline (not associated with a severity grade) in one or both eyes.
Time frame: Day 1 to Day 42
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline | 9 Participants |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline | 16 Participants |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline | 10 Participants |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline | 8 Participants |
| Stage 1 Cohort 1B: AGN-242428 (High Dose) | Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline | 14 Participants |
Secondary
Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h)
Trough plasma concentration (Ctrough) and plasma concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks
Time frame: Day 42
Population: PK population (Stage 2). In Stage 2, post-dose trough plasma concentrations of AGN-242428 or AGN-231868 only were assessed as planned using descriptive statistics.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h) | Predose or Ctrough | 329 pg/mL | Standard Deviation 369 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h) | C0.5h | 444 pg/mL | Standard Deviation 349 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h) | Predose or Ctrough | 1810 pg/mL | Standard Deviation 1950 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h) | C0.5h | 6300 pg/mL | Standard Deviation 3650 |
Secondary
Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h)
Trough tear concentration (Ctrough) and tear concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks
Time frame: Day 42
Population: PK population (Stage 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | Predose Ctrough | 310 ng/mL | Standard Deviation 782 |
| Stage 1 Cohort 1A: AGN-242428 (Low Dose) | Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | C0.5h | 13200 ng/mL | Standard Deviation 31400 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | Predose Ctrough | 1270 ng/mL | Standard Deviation 3560 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | C0.5h | 13700 ng/mL | Standard Deviation 28000 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | Predose Ctrough | 12000 ng/mL | Standard Deviation 17600 |
| Stage 1 Cohort 1A: AGN-231868 (Low Dose) | Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h) | C0.5h | 1030000 ng/mL | Standard Deviation 1710000 |