PMID- 35411579
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20221014
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 15
IP  - 7
DP  - 2022 Jul
TI  - Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in 
      healthy subjects.
PG  - 1654-1663
LID - 10.1111/cts.13280 [doi]
AB  - Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug of 
      tebipenem (TBP), the active moiety, currently in development for treating serious 
      bacterial infections. This study assessed the bioequivalence (BE) of the clinical 
      trial and registration tablet formulations of TBP-PI-HBr and evaluated the effect 
      of food on the pharmacokinetics (PKs) of tebipenem. This was a single center, 
      open-label, randomized, single-dose, three-sequence, four-period crossover, BE, 
      and food-effect study. Subjects received single 600 mg oral doses of TBP-PI-HBr 
      as the reference clinical trial tablet (treatment A) and test registration tablet 
      (treatment B) formulations in alternating sequence while fasting, and then the 
      test formulation under fed conditions. Whole blood samples were collected predose 
      and at specified intervals up to 24 h postdose to evaluate TBP PK parameters. 
      Safety and tolerability were monitored. Thirty-six healthy, adult subjects were 
      enrolled and completed the study. The criteria for BE were met for the TBP-PI-HBr 
      test (registration tablet) and reference (clinical trial tablet) formulations as 
      the 90% confidence intervals for the geometric mean ratios for TBP area under the 
      curve (AUC)(0-t) , AUC(0-inf) , and maximum plasma concentration (C(max) ) fell 
      within the established 80% to 125% BE limits. Dosing with food had no meaningful 
      effect on TBP PK parameters. Five (14%) subjects reported adverse events (AEs) of 
      mild severity. No deaths, serious AEs, or discontinuations due to AEs were 
      reported, and no clinically relevant electrocardiograms, vital signs, or safety 
      laboratory findings were observed. The study results demonstrate the BE of oral 
      TBP-PI-HBr registration and clinical trial tablet formulations and indicate that 
      TBP-PI-HBr can be administered without regard to meals.
CI  - (c) 2022 Spero Therapeutics. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Gupta, Vipul K
AU  - Gupta VK
AD  - Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
FAU - Patel, Gina
AU  - Patel G
AD  - Patel Kwan Consultancy LLC, Madison, Wisconsin, USA.
FAU - Gasink, Leanne
AU  - Gasink L
AD  - Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
FAU - Bajraktari, Floni
AU  - Bajraktari F
AD  - Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
FAU - Lei, Yang
AU  - Lei Y
AD  - Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
FAU - Jain, Akash
AU  - Jain A
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Srivastava, Praveen
AU  - Srivastava P
AD  - Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
FAU - Talley, Angela K
AU  - Talley AK
AD  - Spero Therapeutics, Inc., Cambridge, Massachusetts, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220428
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Carbapenems)
RN  - 0 (Tablets)
RN  - Q2TWQ1I31U (tebipenem)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Carbapenems
MH  - Healthy Volunteers
MH  - Humans
MH  - Tablets
MH  - *Therapeutic Equivalency
PMC - PMC9283737
COIS- Leanne Gasink is a consultant to Spero Therapeutics, Inc. Gina Patel is the 
      principal with Patel Kwan Consultancy LLC, Madison, WI. All other authors were 
      paid employees of Spero Therapeutics, Cambridge, MA, at the time of this study.
EDAT- 2022/04/13 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/07/01
CRDT- 2022/04/12 05:32
PHST- 2022/02/07 00:00 [revised]
PHST- 2021/12/07 00:00 [received]
PHST- 2022/03/23 00:00 [accepted]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/04/12 05:32 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - CTS13280 [pii]
AID - 10.1111/cts.13280 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2022 Jul;15(7):1654-1663. doi: 10.1111/cts.13280. Epub 2022 Apr 
      28.