Novel design of three randomised controlled trials to investigate the clinical efficacy and safety of povidone-iodine/dexamethasone ophthalmic suspension in adenoviral and bacterial conjunctivitis

Session Details

Session Title: Infections

Session Date/Time: Sunday 23/09/2018 | 16:30-18:00

Paper Time: 17:12

Venue: Room A3, Podium 3

First Author: : C.Ta USA

Co Author(s): :    D. Hwang   W. Liu   B. Oliver   A. Narvekar           

Abstract Details

Purpose:

We report a novel design of three ongoing clinical trials (SHP640-301 [S301], SHP640-302 [S302], SHP640-303 [S303]) to assess the safety and efficacy of an ophthalmic suspension of a broad-spectrum antiseptic povidone-iodine (PVP-I, 0.6%) and anti-inflammatory steroid dexamethasone (DEX, 0.1%) in the treatment of adenoviral conjunctivitis (in studies S301 and S302) and bacterial conjunctivitis (in S303). Subjects of any age with suspected infectious conjunctivitis are enrolled in either S301 or S302 if they test positive upon AdenoPlus® screening and clinical signs indicate adenoviral conjunctivitis or enrolled in S303 if they are negative upon AdenoPlus® screening, and clinical signs indicate bacterial conjunctivitis.

Setting:

Phase 3, multicenter, randomized, double-masked, parallel-group, placebo-controlled studies have initiated globally and are enrolling subjects of all ages with suspected bacterial or adenoviral conjunctivitis. Current/planned study sites across North America, South America, Asia/Pacific, Europe, and Middle East/Africa number approximately 100 for study S301, 35 for S302, and 90 for S303.

Methods:

Adenovirus-positive subjects are enrolled in S301 (2:2:1 randomization: PVP-I 0.6%/DEX 0.1%, PVP-I 0.6%, or placebo) or S302 (1:1 randomization: PVP-I 0.6%/DEX 0.1% or placebo). Subjects negative for adenovirus but with signs of bacterial conjunctivitis are randomized 3:1:3 to PVP-I 0.6%/DEX 0.1%, PVP-I 0.6%, or placebo (S303). One drop of study drug is instilled in each eye 4x daily for 7 days. Post-baseline visits occur on Day 3 (+1 window), Day 5-6, Day 8 (+1), and Day 12 (+2). The primary outcome is clinical resolution (absence of bulbar conjunctival injection and conjunctival discharge) in study eye at the Day 5/6 visit.

Results:

The estimated completion of these trials is in 2019 with planned sample sizes of approximately 930 (S301: PVP-I/DEX, n~372; PVP-I, n~372, placebo, n~186), 284 (S302: PVP-I/DEX, n~142; placebo, n~142), and 721 (S303: PVP-I/DEX, n~309; PVP-I, n~103, placebo, n~309). Study results will be reported after completion of the trials.

Conclusions:

Currently there is no medication approved for the safe and efficacious treatment of both viral and bacterial causes of acute infectious conjunctivitis. Three Phase 3, multicenter, randomized controlled trials were designed to investigate whether PVP-I 0.6%/DEX 0.1% ophthalmic suspension compared with PVP-I 0.6% or placebo is safe and efficacious for the treatment of adenoviral or bacterial conjunctivitis. A novel screening and randomization scheme was incorporated in the design of the three studies to address the special challenges of ascertaining the efficacy and safety of the drug combination and each of its components against both adenoviral and bacterial pathogens.

Financial Disclosure:

... has significant investment interest in a company producing, developing or supplying product or procedure presented, ... receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented, ... is employed by a for-profit company with an interest in the subject of the presentation