A Study of the Drugs AGN-242428 and AGN-231868 in Participants With Dry Eye Disease

Dry Eye Disease Clinical Trial

Official title:

A Multicenter, Vehicle-controlled, Double-Masked, Randomized Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of AGN-242428 and AGN-231868 in Participants With Dry Eye Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04030962
• Other study ID #: 2012-201-005
• Status: Completed
• Phase: Phase 2
• Start date: March 4, 2020
• Est. completion date: March 18, 2022

Study information

• Verified date: March 2023
• Source: Allergan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This will be a 2 stage study in which Stage 1 will evaluate 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 will begin. Stage 2 will also evaluate the safety and tolerability of AGN-242428 and AGN-231868, how effective they are in treating dry eye disease and assess the plasma and tear exposure of both ophthalmic solutions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 292
• Est. completion date: March 18, 2022
• Est. primary completion date: March 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dry Eye Disease
• Dry Eye Syndrome
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• AGN-242428
Ophthalmic solution administered as a topical eye drop
• AGN-231868
Ophthalmic solution administered as a topical eye drop

Other:
• AGN-242428 Vehicle
Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
• AGN-231868 Vehicle
Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop

Drug:
• Lifitegrast
Ophthalmic solution administered as a topical eye drop

Locations

Country	Name	City	State
United States	Andover Eye Associates /ID# 232689	Andover	Massachusetts
United States	Alpine Research Organization, Inc. /ID# 240508	Clinton	Utah
United States	Vision Institute Central /ID# 239910	Colorado Springs	Colorado
United States	Scott and Christie and Associates /ID# 232746	Cranberry Township	Pennsylvania
United States	The Eye Care Institute /ID# 232683	Louisville	Kentucky
United States	Piedmont Eye Center /ID# 232698	Lynchburg	Virginia
United States	Total Eye Care, PA /ID# 232657	Memphis	Tennessee
United States	The Eye Research Foundation /ID# 232696	Newport Beach	California
United States	Cornea and Cataract Consultants of Arizona /ID# 232769	Phoenix	Arizona
United States	Vita Eye Clinic /ID# 232721	Shelby	North Carolina
United States	Advancing Vision Research /ID# 232660	Smyrna	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Allergan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: The incidence of adverse events (safety and tolerability)	The number of participants who experience one or more treatment emergent adverse events (TEAE)	15 Day Treatment Period
Primary	Stage 1: Area under the plasma concentration versus time curve from time 0 to time of the last measurable concentration (AUC0-tlast) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Area under the tear concentration versus time curve from time 0 to time of the last measurable concentration (AUC0-tlast) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Maximum plasma drug concentration (Cmax) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Maximum tear drug concentration (Cmax) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Time of maximum plasma drug concentration (Tmax) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Time of maximum tear drug concentration(Tmax) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Terminal elimination half-life (t1/2) after a single dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-t) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Area under the tear concentration versus time curve from time 0 to the end of the dosing interval (AUC0-t) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Maximum plasma drug concentration (Cmax) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Maximum tear drug concentration (Cmax) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Time of maximum plasma drug concentration (Tmax) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Time of maximum tear drug concentration (Tmax) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Minimum plasma drug concentration at steady state (Cmin,ss) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Minimum tear drug concentration at steady state (Cmin,ss) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Terminal elimination half-life of the study drugs (t1/2) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Accumulation index of drug concentration (AI) following repeat dose administration		Predose and up to 12 hours postdose
Primary	Stage 1: Drop Tolerability Questionnaire Score	Rate of the 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.	15 Day Treatment Period
Primary	Stage 1: Number of patients experiencing one or more adverse events (AEs) during the 15 day treatment period		15 Day Treatment Period
Primary	Stage 1: Potentially clinically significant (PCS) clinical laboratory values	The percentage of participants who have PCS postbaseline clinical laboratory values	15 Day Treatment Period
Primary	Stage 1: Vital sign values (blood pressure, pulse rate, weight, respiration rate, and temperature)	The percentage of participants who have PCS postbaseline vital sign values	15 Day Treatment Period
Primary	Stage 1: Electrocardiogram (ECG) heart rate	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Primary	Stage 1: ECG PR interval	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Primary	Stage 1: ECG QRS duration	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Primary	Stage 1: ECG QT interval	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Primary	Stage 1: ECG QTc	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Primary	Stage 1: Change from baseline in intraocular pressure (IOP)		15 Day Treatment Period
Primary	Stage 1: Change from baseline in best-corrected visual acuity (BCVA)		15 Day Treatment Period
Primary	Stage 1: Change from baseline in slit-lamp biomicroscopy		15 Day Treatment Period
Primary	Stage 1: Change from baseline in dilated fundus examination		15 Day Treatment Period
Primary	Stage 2: The incidence of adverse events (safety and tolerability)	The number of participants who experience one or more treatment emergent adverse events (TEAE)	42 Day Treatment Period
Primary	Stage 2: Potentially clinically significant (PCS) clinical laboratory values	The percentage of participants who have PCS postbaseline clinical laboratory values	42 Day Treatment Period
Primary	Stage 2: Vital sign values (blood pressure, pulse rate, weight, respiration rate, and temperature)	The percentage of participants who have PCS postbaseline vital sign values	42 Day Treatment Period
Primary	Stage 2: Number of patients experiencing one or more adverse events (AEs) during the 42 day treatment period		42 Day Treatment Period
Primary	Stage 2: Electrocardiogram (ECG) heart rate	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Primary	Stage 2: ECG PR interval	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Primary	Stage 2: ECG QRS duration	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Primary	Stage 2: ECG QT interval	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Primary	Stage 2: ECG QTc	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Primary	Stage 2: Change from baseline in intraocular pressure (IOP)		42 Day Treatment Period
Primary	Stage 2: Change from baseline in best-corrected visual acuity (BCVA)		42 Day Treatment Period
Primary	Stage 2: Change from baseline in slit-lamp biomicroscopy		42 Day Treatment Period
Primary	Stage 2: Change from baseline in dilated fundus examination		42 Day Treatment Period
Primary	Stage 2: Drop Tolerability Questionnaire Score	Rate of the 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.	42 Day Treatment Period
Secondary	Stage 2: Plasma exposure of AGN-242428 and AGN-231868 in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks	Plasma samples to determine concentrations will be collected at the nominal times	42 Day Treatment Period
Secondary	Stage 2: Tear exposure of AGN-242428 and AGN-231868 in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks	Tear samples to determine concentrations will be collected at the nominal times	42 Day Treatment Period
Secondary	Stage 2: Tear exposure of active comparator in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks	Tear samples to determine concentrations will be collected at the nominal times	42 Day Treatment Period

External Links

•   Additional information on study locations near you may be found at AllerganClinicalTrials.com.To be considered as a site for current and future Allergan Clinical Trials, please register using the Investigator Databank link.