PMID- 23668634
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20211021
IS  - 2050-6511 (Electronic)
IS  - 2050-6511 (Linking)
VI  - 14
DP  - 2013 May 13
TI  - First human dose-escalation study with remogliflozin etabonate, a selective 
      inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in 
      subjects with type 2 diabetes mellitus.
PG  - 26
LID - 10.1186/2050-6511-14-26 [doi]
AB  - BACKGROUND: Remogliflozin etabonate (RE) is the prodrug of remogliflozin, a 
      selective inhibitor of the renal sodium-dependent glucose transporter 2 (SGLT2), 
      which could increase urine glucose excretion (UGE) and lower plasma glucose in 
      humans. METHODS: This double-blind, randomized, placebo-controlled, single-dose, 
      dose-escalation, crossover study is the first human trial designed to evaluate 
      safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of RE. All 
      subjects received single oral doses of either RE or placebo separated by 
      approximately 2 week intervals. In Part A, 10 healthy subjects participated in 5 
      dosing periods where they received RE (20 mg, 50 mg, 150 mg, 500 mg, or 1000 mg) 
      or placebo (4:1 active to placebo ratio per treatment period). In Part B, 6 
      subjects with type 2 diabetes mellitus (T2DM) participated in 3 dose periods 
      where they received RE (50 mg and 500 mg) or placebo (2:1 active to placebo per 
      treatment period). The study protocol was registered with the NIH clinical trials 
      data base with identifier NCT01571661. RESULTS: RE was generally well-tolerated; 
      there were no serious adverse events. In both populations, RE was rapidly 
      absorbed and converted to remogliflozin (time to maximum plasma concentration 
      [Cmax;Tmax] approximately 1 h). Generally, exposure to remogliflozin was 
      proportional to the administered dose. RE was rapidly eliminated (mean T(1/2) of ~25 
      min; mean plasma T(1/2) for remogliflozin was 120 min) and was independent of dose. 
      All subjects showed dose-dependent increases in 24-hour UGE, which plateaued at 
      approximately 200 to 250 mmol glucose with RE doses >/=150 mg. In T2DM subjects, 
      increased plasma glucose following OGTT was attenuated by RE in a drug-dependent 
      fashion, but there were no clear trends in plasma insulin. There were no apparent 
      effects of treatment on plasma or urine electrolytes. CONCLUSIONS: The results 
      support progression of RE as a potential treatment for T2DM. TRIAL REGISTRATION: 
      ClinicalTrials.gov NCT01571661.
FAU - Kapur, Anita
AU  - Kapur A
FAU - O'Connor-Semmes, Robin
AU  - O'Connor-Semmes R
FAU - Hussey, Elizabeth K
AU  - Hussey EK
FAU - Dobbins, Robert L
AU  - Dobbins RL
FAU - Tao, Wenli
AU  - Tao W
FAU - Hompesch, Marcus
AU  - Hompesch M
FAU - Smith, Glenn A
AU  - Smith GA
FAU - Polli, Joseph W
AU  - Polli JW
FAU - James, Charles D Jr
AU  - James CD Jr
FAU - Mikoshiba, Imao
AU  - Mikoshiba I
FAU - Nunez, Derek J
AU  - Nunez DJ
LA  - eng
SI  - ClinicalTrials.gov/NCT01571661
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130513
PL  - England
TA  - BMC Pharmacol Toxicol
JT  - BMC pharmacology & toxicology
JID - 101590449
RN  - 0 (Blood Glucose)
RN  - 0 (Electrolytes)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Pyrazoles)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - TR0QT6QSUL (remogliflozin etabonate)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Blood Glucose/metabolism
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Diarrhea/chemically induced
MH  - Dizziness/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Electrolytes/urine
MH  - Female
MH  - Glucosides/adverse effects/pharmacokinetics/*therapeutic use
MH  - Headache/chemically induced
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/pharmacokinetics/therapeutic use
MH  - Insulin/blood
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Molecular Structure
MH  - Pyrazoles/adverse effects/pharmacokinetics/*therapeutic use
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Treatment Outcome
PMC - PMC3700763
EDAT- 2013/05/15 06:00
MHDA- 2015/05/12 06:00
PMCR- 2013/05/13
CRDT- 2013/05/15 06:00
PHST- 2012/02/17 00:00 [received]
PHST- 2013/04/12 00:00 [accepted]
PHST- 2013/05/15 06:00 [entrez]
PHST- 2013/05/15 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
PHST- 2013/05/13 00:00 [pmc-release]
AID - 2050-6511-14-26 [pii]
AID - 10.1186/2050-6511-14-26 [doi]
PST - epublish
SO  - BMC Pharmacol Toxicol. 2013 May 13;14:26. doi: 10.1186/2050-6511-14-26.