An investigation of the formulation of lansoprazole can be safely treat gastroesophageal reflux disease in newborns and infants as old as 1 year of age according to the results of two Phase I trials in a poster presented at the annual meeting of the Pediatric Academic Societies.
Dr. Margaret Ann Springer reported that the new formulation of lansoprazole (Prevacid), a proton pump inhibitor, relieves symptoms in most babies in the two studies. After 5 days, researchers saw improvements in 79% of 24 newborns and 88% of 24 older infants.
Gastroesophageal reflux disease (GERD) do not worsen in any of the babies. Although four newborns and older babies had adverse effects related to treatment, the baby did not have to be withdrawn from the trial because of side effects.
All infants met criteria for clinically evident prudent GERD before being enrolled, said Dr. Springer, the Louisiana State University in Shreveport, in an interview at the reunion. These include feeding intolerance and refusal to eat, vomiting after feeding, irritability and / or crying while being fed; tonnage back, altered growth, and respiratory symptoms. “Babies can die from the pneumonia. Infants can stop your heart enough to stop breathing. Babies do not gain weight and grow, because every time you eat it hurts.”
Lansoprazole is approved for short-term treatment of GERD in children aged 1-17 years. Dr. Springer said the Food and Drug Administration agreed to the test in infants and newborns because it is very symptomatic GERD in this population. An estimated third to half of babies have some symptoms of GERD, approximately 10% are severe cases that require special care.
TAP Pharmaceutical Products Inc. Lake Forest, Illinois, manufacturer of Generic Lansoprazole, sponsored the two open-label trial that enrolled children in the United States and Poland. The Phase I trial enrolled 24 newborn term or postterm infants. The mean age was 3.7 weeks, mean weight, 3015 g The second phase I trial enrolled 24 children from 4 weeks to 1 year. Their average age was 24.1 weeks, average weight, 6379 g.
Clinical Packaging reconstituted powder granules of lansoprazole in sterile water. For newborns, using a concentration of 1 mg / ml, which was delivered once daily at a 0.5-mg/kg or 1.0-mg/kg dose. The older children were given a concentration 2-mg/mL a 1.0-mg/kg or 2.0-mg/kg daily dose.
Lansoprazole may be administered with a syringe, intraorally, or through a gastronomy tube. A pharmacokinetic analysis of children found 10 weeks or less had “substantially increased exposure to lansoprazole compared with older infants.
Each trial included 24 hours of pH profiles of six babies to determine changes in intragastric levels. The researchers used a pH level of 4 or more as an order to show the drug was reduced stomach acid. The average percentage of time that pH levels greater than 4 was increased from 77% on day 1 to 97% during the 5 days for infants to 0.5 mg / kg per day of drug and 59% to 99% for the 1.0 - mg / kg daily dose.
The older children substantially increased the percentage of time in their pH profiles reached the goal, but the result was not so great. Proportions were 50% to 85% of the daily 1.0-mg/kg dose and 52% to 84% at 2.0 mg / kg per day.
Treatment-related adverse events included two cases of flushing, anemia and an increase of transaminases in newborn infants, plus an increase in liver enzymes in a baby older. Two serious adverse events, respiratory distress syndrome and viral pneumonia, which occurred after the last day of lansoprazole, but was not considered related to the study.
Dr. Springer said the drug company has already launched a trial of efficacy and safety based on the results. The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association and American Academy of Pediatrics.
