title: Phase I and phase IB clinical trials for the noninvasive evaluation of intestinal lactase with 4-galactosylxylose (gaxilose).
abstract: OBJECTIVE
  Hypolactasia is widespread, yet reliable diagnostic tests are lacking. A new test based on oral administration of 4-galactosylxylose (gaxilose) and urine or serum measurement of D-xylose after cleavage by intestinal lactase is under clinical development. We investigated the optimal dose of gaxilose and calculate cutoff values of D-xylose for that dose.
  
  
  METHODS
  In the randomized, dose-finding, phase I study, urine and serum pharmacokinetics of D-xylose were determined after oral administration of 6 ascending doses of gaxilose (and placebo) to 12 healthy adult volunteers. In the open, parallel, phase Ib study, 30 volunteers received the doses established for the urine and blood tests and D-xylose was measured. Cutoff values were calculated as 1.96 × SD below the mean value. Safety was assessed through reporting of adverse events.
  
  
  RESULTS
  Gaxilose administration showed a progressive, dose-dependent increase in D-xylose in urine and serum. An optimal gaxilose dose of 0.45 g and urine collection periods of 4 and 5 hours were selected for further studies. For the blood test, a 2.7 g dose was selected and C max measured at 90 minutes. The calculated cutoff values of D-xylose for normal lactase activity were 27.58 and 37.87 mg for the 4- and 5-hour urine tests, respectively, and 0.97 mg/dL for the blood test. There were no treatment-related adverse events.
  
  
  CONCLUSIONS
  The methodology described provides a simple, safe test for the evaluation of lactase activity in vivo. Further evaluation of the test as a noninvasive diagnosis of hypolactasia is ongoing in patients with lactose intolerance.
authors: Departamento de Bioquímica, Instituto de Investigaciones Biomédicas Alberto Sols, Facultad de Medicina de la Universidad Autónoma de Madrid, Madrid, Spain.
authors: Carmen
authors: C
authors: Hermida
authors: Pedro
authors: P
authors: Guerra
authors: Oscar H
authors: OH
authors: Martínez-Costa
authors: Valentina
authors: V
authors: Sánchez
authors: José J
authors: JJ
authors: Sánchez
authors: Jesús
authors: J
authors: Solera
authors: Alfonso
authors: A
authors: Fernández-Mayoralas
authors: Rosa
authors: R
authors: Codoceo
authors: Jesús
authors: J
authors: Frías
authors: Juan J
authors: JJ
authors: Aragón
mesh_terms: D000328:Adult; D004187:Disaccharides / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007422:Intestines / Q000201:enzymology*; D043322:Lactase / Q000172:deficiency / Q000378:metabolism*; D007787:Lactose Intolerance / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D016037:Single-Blind Method; D014994:Xylose / Q000378:metabolism
chemical_list: D004187:Disaccharides; C073827:4-O-galactopyranosylxylose; D014994:Xylose; D043322:Lactase