1996. Single Ascending Dose Safety, Tolerability, and Pharmacokinetics of KBP-7072, a Novel Third Generation Tetracycline 
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall

Single Ascending Dose Safety, Tolerability, and Pharmacokinetics of KBP-7072, a Novel Third Generation Tetracycline   

Bin Zhang, MD1, Yanli Wang, MS2, Yanhua Chen, MS2, Fred Yang, PhD1

KBP Biosciences USA Inc. Princeton NJ USA1, KBP Biosciences Co. Ltd. Jinan China2

 

Background:  KBP-7072 is a novel aminomethylcycline exhibiting broad-spectrum activity against Gram+ and Gram- multidrug resistant bacterial isolates and strains. 

Methods:  This was a randomized, double-blind, placebo-controlled, sequential parallel group, single ascending dose study in healthy adults to evaluate the safety, tolerability, and pharmacokinetics (PK) of KBP-7072 following oral administration and with an open label food effect panel.  Under fasting conditions, 5 fasting cohorts (30 mg, 100 mg, 300 mg, 600 mg, and 1000 mg) were planned with 8 subjects (6 KBP-7072; 2 placebo) in each cohort.  Dose escalation stopped following the 300 mg cohort.  An additional 6 subjects received a single oral dose (100 mg) under fed conditions.  Safety, tolerability, and PK were evaluated across different doses and food effect was compared between 100 mg fasting and 100 mg fed dose cohorts.  

Results:  30 subjects (male: 76.7%; 18-52 years) were enrolled (8 in each of 3 fasting cohorts, 6 in the fed cohort). All treatment-emergent adverse events (TEAEs) were of mild intensity and most TEAEs were assessed as either unrelated or probably unrelated to treatment. No serious adverse events were reported. Elevated alanine aminotransferase was reported in 6 subjects (2 in the 30 mg, 1 in the 100 mg, 3 in the 300 mg cohort). All were asymptomatic and recovered without intervention. No liver function abnormalities were observed in the fed cohort. Data included in the table below show a clear linear dose response as well as an obvious food effect on PK parameters.  

 

PK Parameter

Statistic

KBP-7072
30 mg Fasted
(N = 6)

KBP-7072
100 mg Fasted
(N = 6)

KBP-7072
300 mg Fasted
(N =6)

KBP-7072
100 mg Fed
(N = 6)

Cmax (ng/mL)

Mean (SD)

206.3 (40.58)

536.2 (167.6)

1094.0 (134.3)

173.0 (26.11)

Tmax (hr)

Median (range)

2.00

(1.00, 2.00)

2.00

(1.00, 4.00)

2.00

(1.00, 2.00)

4.00

(2.00, 4.00)

AUC0-inf (h*ng/mL)

Mean (SD)

3277 (496.7)

9455 (2890)

20469 (3883)

3383 (617.2)

t1/2 (hr)

Mean (SD)

24.70 (2.442)

29.30 (5.627)

46.26 (22.27)

28.36 (8.043)

Conclusion:  This study demonstrated that KBP-7072 was safe and generally well-tolerated at single doses up to and including 300 mg.

Bin Zhang, PhD, KBP Biosciences USA Inc, Princeton, NJ

Disclosures:

B. Zhang, KBP Biosciences USA Inc: Employee , Salary

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