Clinical Study of Caffeine for Apnea of Prematurity

A Phase III Clinical Study of NPC-11 in the Treatment of Apnea of Prematurity. - Investigation of Safety, Efficacy and Pharmacokinetics of Caffeine Citrate -

The aim of the present Phase III study is to evaluate the safety, efficacy and pharmacokinetics of Caffeine Citrate for treatment of apnea of prematurity in Japan.

Inclusion Criteria:

• Postconceptional age between 28 weeks and 33 weeks, and over 24 hours after birth.
• At least 6 episodes of apnea (>20 seconds in duration) in 24 hours.
• Signed written informed consent from parent(s) or legal guardian(s).

Exclusion Criteria:

• Apnea due to: hypoxic-ischemic encephalopathy, meningitis, seizures, Grade III or IV intracranial hemorrhage, CNS depression from drugs administered to the mother during delivery, periventricular leukomalacia, pneumonia which does not improve even if it treats, hemoglobin< 10 g/dL, sepsis, shock which does not improve even if it treats, blood pH<7.2 on 2 consecutive determinations in spite of correction, serum calcium concentration <7.0 mg/dL which does not improve even if it treats, serum glucose concentration <4.0 mg/dL which does not improve even if it treats, congestive heart failure, symptomatic patent ductus arteriosus, rectal temperature>38.5 °C on 2 consecutive readings, rectal temperature< 35 °C on 2 consecutive readings, obstructive apnea.
• Blood urea nitrogen >20 mg/dL, serum creatinine >1.5 mg/dL.
• Serum AST or ALT >3 times the upper limit of normal.
• Requirement of mechanically-assisted ventilation ( containing nasal CPAP, nasal DPAP).
• Previous treatment with methylxanthines within 7 days prior to study enrollment.
• Previous treatment with H2 antagonists (i.e., cimetidine or ranitidine) within 7 days prior to study enrollment.
• Receiving or experiencing the effects of CNS-active medication at the time of enrollment.
• Participant of other clinical trial within 6 months.
• Inappropriate to enter this clinical trial judged by the investigator in charge.