Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AKB-9778 Ophthalmic Solution

Phase 1 Multi Center, Double-Masked, Randomized, Placebo-Controlled, Multiple Ascending Dose Cohort Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single or Twice Daily Doses of AKB-9778 Ophthalmic Solution

The purpose of this Phase 1b study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of AKB-9778 ophthalmic solution (eye drops) administered for 7 days in adults. The study is a double-masked, multiple- ascending dose trial and will enroll four cohorts of up to 12 subjects. Dose cohorts will receive increasing doses of AKB-9778 ophthalmic solution or vehicle-matched placebo daily for 7 days. Cohort 5 will enroll subjects with open angle glaucoma or ocular hypertension who will continue current prostaglandin therapy during the study. Cohort 5 subjects will receive the maximum tolerated dose from the previous cohorts.

Study Overview

• Status: Completed
• Conditions: Primary Open Angle Glaucoma; Ocular Hypertension
• Intervention / Treatment: Drug: AKB-9778 Ophthalmic Solution; Drug: Placebo Ophthalmic Solution

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Aged > 18 years to 70 years inclusive in Cohort 1; aged ≥ 45 to 70 years inclusive in Cohorts 2-4, aged 18 to 80 years inclusive in Cohort 5.
• For subjects in Cohort 1, IOP between 12 and 23 mm Hg (inclusive). For subjects in Cohorts 2-4, IOP between 16 and 23mm Hg (inclusive). For subjects in Cohort 5, IOP between 17 and 27 mm Hg (inclusive).
• Central corneal thickness of 480 to 600 μm, inclusive
• For subjects in Cohort 5, diagnosis of OAG or OHT
• For subjects in Cohort 5, currently receiving prostaglandin therapy for IOP lowering

Key Exclusion Criteria:

• Diagnosis of any form of glaucoma in Cohorts 1-4
• Clinically significant eye trauma within 6 months of screening
• Any intraocular ophthalmic procedure within 6 months of screening
• Any ocular inflammation within 90 days of screening or a history of recurrent uveitis in either eye
• Subjects with any known chronic ocular disease (other than incipient cataract or refractive error)
• Any condition preventing valid applanation tonometry measurement, e.g., clinically significant corneal disease, refractive surgery
• Visual acuity (VA) worse than 20/30 in either eye, For Cohort 5 VA worse than 20/100 in either eye

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: AKB-9778 Ophthalmic Solution; Up to 4 daily dose levels of AKB-9778 Ophthalmic Solution will be evaluated. Doses will be administered in both eyes daily for 7 days.	Drug: AKB-9778 Ophthalmic Solution; AKB-9778 Ophthalmic Solution
PLACEBO_COMPARATOR: Vehicle Control Ophthalmic Solution; Matched vehicle-control ophthalmic solution will be administered in both eyes daily for 7 days.	Drug: Placebo Ophthalmic Solution; Matched vehicle-control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		Baseline to Day 7
Vital sign- systolic and diastolic blood pressure	Systolic and diastolic blood pressure in mmHg	Baseline to Day 7
Complete blood count	White blood cells with differential, hemoglobin, hematocrit and platelet count	Baseline to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular pressure	Intraocular pressure in mmHg	Baseline to Day 7
AKB-9778 concentration	Measurement of AKB-9778 in plasma after drug administration	Baseline to Day 7

Collaborators and Investigators

• Sponsor: Aerpio Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 2, 2019
• Primary Completion (ACTUAL): December 15, 2019
• Study Completion (ACTUAL): December 15, 2019

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: February 24, 2020
• First Posted (ACTUAL): February 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: AKB-9778-CI-OS-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No