911. A Phase1, Open-Label, Evaluation of the Single-Dose Pharmacokinetics of Delafloxacin (DLX) in Subjects With and Without Hepatic Impairment
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall

Background: Delafloxacin (DLX) is an investigational broad spectrum fluoroquinolone with activity against methicillin-resistant S. aureus (MRSA) and susceptible gram-negative bacteria. DLX is in Phase 3 development for ABSSSI.

Methods: This was a Phase 1 PK study in subjects with mild, moderate, or severe hepatic impairment (n=6 per category). Healthy subjects (18 total) were closely matched to the impaired subjects for age, weight and gender. DLX was given as a 300‑mg 1‑hr IV infusion, and plasma DLX concentrations determined. The effects of hepatic impairment were assessed by ANOVA of log-transformed values for AUC, Cmax, and systemic clearance, with hepatic group as a fixed effect. Each impairment group was compared to its matching healthy group, and also to pooled healthy subjects.

Results: Mean AUCinf and Cmax in each impairment group were not significantly different from the pooled healthy subjects (p>0.05). The 90% CI of the ratios of LS means did not indicate significant differences between the impairment groups and pooled healthy subjects. No significant trend was observed for any PK parameter versus the ordered normal and impairment categories (p>0.05). AUCinf and Cmax for the impairment groups were similar to historic values in Phase 1 studies with healthy subjects. TEAEs (10 out of 40 subjects) were mild or moderate.

AUCinf (hr*ug/mL)

Impairment Group

N

Geo LS Mean

90% CI of
Geo LS Mean

Comp.

Ratio of
Geo LS Means (%)

90% CI of
the Ratio (%)

A Mild

6

23.25

(19.91, 27.14)

A/D

114.44

(95.57, 137.03)

B Moderate

6

23.32

(19.97, 27.22)

B/D

114.78

(95.86, 137.44)

C Severe

6

23.38

(20.02, 27.29)

C/D

115.09

(96.11, 137.80)

D Normal

17

20.31

(18.53, 22.27)

--

--

--

Conclusion: The exposure and clearance of DLX in subjects with mild, moderate, and severe hepatic impairment did not differ significantly from pooled, matched healthy subjects. No trend in DLX exposure was observed with increasing impairment. The exposure of DLX in subjects with hepatic impairment was similar to historic Phase 1 values. It is suggested that dose adjustment of DLX is not required for subjects with mild, moderate, or severe hepatic impairment.

Randall Hoover, Ph.D.1, Megan Quintas, BA1, Laura Lawrence, BS1, Sriram Gunda, Ph.D.2, Eugene Sun, MD1 and Sue Cammarata, MD1, (1)Melinta Therapeutics, New Haven, CT, (2)PPD, Richmond, VA

Disclosures:

R. Hoover, Melinta Therapeutics: Consultant , Consulting fee

M. Quintas, Melinta Therapeutics: Employee , Salary

L. Lawrence, Melinta Therapeutics: Employee , Salary

S. Gunda, PPD: Research Contractor , Salary

E. Sun, Melinta Therapeutics: Employee , Salary

S. Cammarata, Melinta Therapeutics: Employee , Salary

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