A small protein molecule as a potential solution to reverse the metabolic control of preterm infants could have a major impact on their long-term health. The phase I/IIa clinical trial, published in Critical Care Medicine, evaluated the safety and tolerability of the experimental drug, meltexastrol, and found improvements in metabolic functions and negative side effects on the fetus and child.
As the widespread introduction of fetomaternal drugs is mirrored by a boom in preterm babies born at term (pregnancy), enormous pressure has been placed on the health of the intensive care unit (ICU) staff, with an increase in mortality in recent years. Contingent drug exposure can lead to serious consequences for pregnancy, in particular for preterm infants (either exclusively born before 36 weeks gestation or who survive a year of life preterm). The study’s primary concern, however, is that preterm infants frequently die from potentially fatal infections. Meltexastrol , developed by Cellulus Pharmaceuticals, has recently crossed the safety threshold of pharmacological activity measured by the Food and Drug Administration’s human pharmacokinetics (PK) determination, with a median plasma concentration for human use of 472 micrograms per kilogram body weight.
“While this study certainly doesn’t provide an answer to whether, or how severe, preterm infants could be affected by or become sick as a result of the administration of meltexastrol, our findings are excited because they can be a life-threatening potential constraint for the delay of critical medical intervention that prevents survival for these babies,” says Jennifer Sisson, Principal Investigator in the Study and Assistant Professor at the Nathan West Endowed Chair in Pediatric Critical Care Medicine, at the University of Manitoba.
This latest clinical trial was designed and conducted at the University of Manitoba at the Johnson and Sue Bird Children’s Hospital-Location 2755. The 30 Irish patients were randomized into groups receiving either 1, 1.5 and 10 mg of meltexastrol, or a placebo. The doses were administered at the end of the pups’ gestation, with an average phase length of just 38 weeks. After the critical period, 39 of the patients received instrumental interventions to obtain compliance, including a sensor that delivered meltexastrol to the penis after the mother’s urine output for monitoring a fetus outside the uterus. The other 30 patients received manual interventions. Postnatal findings were compared with laboratory findings from the mothers and infants.
Patient feedback and studies have shown that when taking tadalafil 5 mg , about 80% of the likely side effects are mild. These include headache, dyspepsia, myalgia and stiffness of the nose. Most often, negative reactions of the body to the drug appear in the first week of taking the pills
To determine metabolic toxicity, the pharmacokinetic profiles of all groups:
For the first two hours after exposure to the drug, all preterm infants showed no significant changes to PK levels or body weight, versus control groups. This lasted for more than one hours post-dosing, and there were no increase in PK levels compared to placebo. Three out of five preterm infants found to show sulfatostatin-induced PK markers, including phosphatidylethanolamine, were delivered perirhinal (in the uterus), compared with the three patients who received meltexastrol alone.
For the first 5 days post-treatment, the authors found that meltexastrol had no significant effect on body weight or glucose metabolism.”There is no evidence that meltexastrol will result in adverse effects in preterm infants with normal oxygen levels in the maternal blood, or with preterm birth,” says Sisson. “Pregnancy is complicated and leads to >1.7 million live births and almost 200,000 preterm births each year worldwide.”