SETTLE™ - Bioniche Animal Health

SETTLE Challenge Study

Good Clinical Practices (GCP) Intrauterine Streptococcus zooepidemicus Challenge^8,9

SETTLE demonstrates intravenous and
intrauterine efficacy against a challenge with a
recognized pathogen in a double blinded, fully
monitored and certified, GCP regulatory study.

Although not necessary for US and Canadian registration purposes, full GCP studies
are the standard for human and veterinary
registrations in most of the world.

Generally, endometritis is treated with hormones and
intrauterine or systemic antibiotics over a number of days. It has been demonstrated that a single dose of SETTLE normalizes the uterine inflammatory response and enhances the resolution of infectious endometritis and endometriosis.^2-4,6,7

In this study, SETTLE was evaluated for its ability to treat an experimentally induced bacterial infection in endometritis-susceptible mares.

Thirty endometritis susceptible mares were experimentally infected with ^1x109 cfu Streptococcus zooepidemicus, a recognized intrauterine pathogen. Once the infection was confirmed, the mares were randomly assigned to one of three treatment groups; SETTLE intravenously (n=10), SETTLE by intrauterine instillation (n=10) or placebo (n=5+5).

Twenty four hours later, SETTLE had cleared the infection from 5/10 mares following intravenous administration and from 6/10 mares following intrauterine administration.

At seven days post-treatment, 7/10 mares and 8/10 mares respectively, demonstrated negative bacterial cultures. All placebo-treated mares remained infected during the same periods.

The results were statistically significant for both the intravenous and intrauterine routes of administration
(p<0.001).

Additionally, mares treated with SETTLE demonstrated a statistically significant decrease (p<0.001) in the number of PMN in biopsy samples at 24 hours and 7 days post-treatment when compared to the samples at pre-treatment.

Furthermore, a statistically significant reduction
(p<0.001) was observed in the volume of uterine fluids when comparing the mares at pre-treatment
to the mares at 7 days post-treatment.

Challenge Data Results

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In spite of using a more virulent bacterial challenge than would normally be seen in the field (^{1 x 10 9} cfu), SETTLE performed extremely well as a stand-alone therapy with up to 60% clearance at 24 hours.

No other therapy was provided in this study. No antibiotics or uterine lavage were used.

Efficacy results for intravenous and intrauterine administration of SETTLE were the same (no statistical difference).