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

Sponsor
Allergan (Industry)
Overall Status
Completed
CT.gov ID
NCT04030962
Collaborator
(none)
292
11
13
24.4
26.5
1.1

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
292 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 4, 2020
Actual Primary Completion Date :
Mar 18, 2022
Actual Study Completion Date :
Mar 18, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Stage 1: AGN-242428 Cohort 1A

Administration of AGN-242428 ophthalmic solution

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

Experimental: Stage 1: AGN-242428 Cohort 1B

Administration of AGN-242428 ophthalmic solution

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

Experimental: Stage 1: AGN-242428 Cohort 1C

Administration of AGN-242428 ophthalmic solution

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

Experimental: Stage 1: AGN-231868 Cohort 1A

Administration of AGN-231868 ophthalmic solution

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

Experimental: Stage 1: AGN-231868 Cohort 1B

Administration of AGN-231868 ophthalmic solution

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

Experimental: Stage 1: AGN-231868 Cohort 1C

Administration of AGN-231868 ophthalmic solution

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

Placebo Comparator: Stage 1: AGN-242428 Vehicle

Administration of matching placebo (vehicle) ophthalmic solution

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

Placebo Comparator: Stage 1: AGN-231868 Vehicle

Administration of matching placebo (vehicle) ophthalmic solution

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

Experimental: Stage 2: AGN-242428 Group 1

Administration of AGN-242428 ophthalmic solution

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

Experimental: Stage 2: AGN-242428 Vehicle Group 2

Administration of matching placebo (vehicle) ophthalmic solution

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

Experimental: Stage 2: AGN-231868 Group 3

Administration of AGN-231868 ophthalmic solution

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

Experimental: Stage 2: AGN-231868 Vehicle Group 4

Administration of matching placebo (vehicle) ophthalmic solution

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

Active Comparator: Comparator Ophthalmic Solution

Administration of comparator ophthalmic solution

Drug: Comparator ophthalmic solution
Ophthalmic solution administered as a topical eye drop

Outcome Measures

Primary Outcome Measures

  1. Stage 1: The incidence of adverse events (safety and tolerability) [15 Day Treatment Period]

    The number of participants who experience one or more treatment emergent adverse events (TEAE)

  2. 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]

  3. 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]

  4. Stage 1: Maximum plasma drug concentration (Cmax) after a single dose administration [Predose and up to 12 hours postdose]

  5. Stage 1: Maximum tear drug concentration (Cmax) after a single dose administration [Predose and up to 12 hours postdose]

  6. Stage 1: Time of maximum plasma drug concentration (Tmax) after a single dose administration [Predose and up to 12 hours postdose]

  7. Stage 1: Time of maximum tear drug concentration(Tmax) after a single dose administration [Predose and up to 12 hours postdose]

  8. Stage 1: Terminal elimination half-life (t1/2) after a single dose administration [Predose and up to 12 hours postdose]

  9. Stage 1: Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-τ) following repeat dose administration [Predose and up to 12 hours postdose]

  10. Stage 1: Area under the tear concentration versus time curve from time 0 to the end of the dosing interval (AUC0-τ) following repeat dose administration [Predose and up to 12 hours postdose]

  11. Stage 1: Maximum plasma drug concentration (Cmax) following repeat dose administration [Predose and up to 12 hours postdose]

  12. Stage 1: Maximum tear drug concentration (Cmax) following repeat dose administration [Predose and up to 12 hours postdose]

  13. Stage 1: Time of maximum plasma drug concentration (Tmax) following repeat dose administration [Predose and up to 12 hours postdose]

  14. Stage 1: Time of maximum tear drug concentration (Tmax) following repeat dose administration [Predose and up to 12 hours postdose]

  15. Stage 1: Minimum plasma drug concentration at steady state (Cmin,ss) following repeat dose administration [Predose and up to 12 hours postdose]

  16. Stage 1: Minimum tear drug concentration at steady state (Cmin,ss) following repeat dose administration [Predose and up to 12 hours postdose]

  17. Stage 1: Terminal elimination half-life of the study drugs (t1/2) following repeat dose administration [Predose and up to 12 hours postdose]

  18. Stage 1: Accumulation index of drug concentration (AI) following repeat dose administration [Predose and up to 12 hours postdose]

  19. Stage 1: Drop Tolerability Questionnaire Score [15 Day Treatment Period]

    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.

  20. Stage 1: Number of patients experiencing one or more adverse events (AEs) during the 15 day treatment period [15 Day Treatment Period]

  21. Stage 1: Potentially clinically significant (PCS) clinical laboratory values [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline clinical laboratory values

  22. Stage 1: Vital sign values (blood pressure, pulse rate, weight, respiration rate, and temperature) [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline vital sign values

  23. Stage 1: Electrocardiogram (ECG) heart rate [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  24. Stage 1: ECG PR interval [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  25. Stage 1: ECG QRS duration [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  26. Stage 1: ECG QT interval [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  27. Stage 1: ECG QTc [15 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  28. Stage 1: Change from baseline in intraocular pressure (IOP) [15 Day Treatment Period]

  29. Stage 1: Change from baseline in best-corrected visual acuity (BCVA) [15 Day Treatment Period]

  30. Stage 1: Change from baseline in slit-lamp biomicroscopy [15 Day Treatment Period]

  31. Stage 1: Change from baseline in dilated fundus examination [15 Day Treatment Period]

  32. Stage 2: The incidence of adverse events (safety and tolerability) [42 Day Treatment Period]

    The number of participants who experience one or more treatment emergent adverse events (TEAE)

  33. Stage 2: Potentially clinically significant (PCS) clinical laboratory values [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline clinical laboratory values

  34. Stage 2: Vital sign values (blood pressure, pulse rate, weight, respiration rate, and temperature) [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline vital sign values

  35. Stage 2: Number of patients experiencing one or more adverse events (AEs) during the 42 day treatment period [42 Day Treatment Period]

  36. Stage 2: Electrocardiogram (ECG) heart rate [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  37. Stage 2: ECG PR interval [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  38. Stage 2: ECG QRS duration [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  39. Stage 2: ECG QT interval [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  40. Stage 2: ECG QTc [42 Day Treatment Period]

    The percentage of participants who have PCS postbaseline ECG

  41. Stage 2: Change from baseline in intraocular pressure (IOP) [42 Day Treatment Period]

  42. Stage 2: Change from baseline in best-corrected visual acuity (BCVA) [42 Day Treatment Period]

  43. Stage 2: Change from baseline in slit-lamp biomicroscopy [42 Day Treatment Period]

  44. Stage 2: Change from baseline in dilated fundus examination [42 Day Treatment Period]

  45. Stage 2: Drop Tolerability Questionnaire Score [42 Day Treatment Period]

    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.

Secondary Outcome Measures

  1. 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 [42 Day Treatment Period]

    Plasma samples to determine concentrations will be collected at the nominal times

  2. 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 [42 Day Treatment Period]

    Tear samples to determine concentrations will be collected at the nominal times

  3. Stage 2: Tear exposure of active comparator in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks [42 Day Treatment Period]

    Tear samples to determine concentrations will be collected at the nominal times

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Cornea and Cataract Consultants of Arizona /ID# 232769 Phoenix Arizona United States 85032
2 The Eye Research Foundation /ID# 232696 Newport Beach California United States 92663-3637
3 Vision Institute Central /ID# 239910 Colorado Springs Colorado United States 80907-7529
4 The Eye Care Institute /ID# 232683 Louisville Kentucky United States 40206
5 Andover Eye Associates /ID# 232689 Andover Massachusetts United States 01810
6 Vita Eye Clinic /ID# 232721 Shelby North Carolina United States 28150
7 Scott and Christie and Associates /ID# 232746 Cranberry Township Pennsylvania United States 16066
8 Total Eye Care, PA /ID# 232657 Memphis Tennessee United States 38119-5745
9 Advancing Vision Research /ID# 232660 Smyrna Tennessee United States 37167
10 Alpine Research Organization, Inc. /ID# 240508 Clinton Utah United States 84015-8562
11 Piedmont Eye Center /ID# 232698 Lynchburg Virginia United States 24502

Sponsors and Collaborators

  • Allergan

Investigators

  • Study Director: ALLERGAN INC., Allergan

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Allergan
ClinicalTrials.gov Identifier:
NCT04030962
Other Study ID Numbers:
  • 2012-201-005
First Posted:
Jul 24, 2019
Last Update Posted:
Apr 11, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 11, 2022