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.

Study Overview

• Status: Completed
• Conditions: Apnea of Prematurity
• Intervention / Treatment: Drug: NPC-11 for intravenous or oral administration.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Kutsukake, Aichi, Japan
      • Fujita Health University Hospital
  • Osaka
    • Izumi, Osaka, Japan
      • Osaka Medical Center and Research Institute for Maternal and Child Health
  • Tokyo
    • Fuchu, Tokyo, Japan
      • Tokyo Metropolitan Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NPC-11; Loading Dose (Day 1): Caffeine citrate 20 mg/kg body weight will be administered intravenously using a syringe infusion pump over 30 minutes.; Maintenance Dose (Day 2～Day 10): After an interval 24 hours, caffeine citrate 5 mg/kg body weight will be administered intravenously (over 10 minutes) or orally if the patients will be able to receive oral administration once a day. The maintenance dose can be increased to a maximum 10 mg/kg caffeine citrate once a day if apnea persists.

Drug: NPC-11 for intravenous or oral administration.; NPC-11, Each vial (3mL) contains 60 mg caffeine citrate (equivalent to 30mg caffeine).; Other Names: caffeine citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Success rates for controlling of apnea episode in each observation day (at least 50% reduction of apnea episodes from baseline)	1, 2, 3, 4, 5, 6,7, 8, 9 and 10 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of frequency of apnea episode from baseline in each observation day		1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day
Time to event：Days until next events occurred	Time to event：Days until next events occurred. The definition of events are, Not at least 50% reduction of apnea episode Not improving the frequency of episode from baseline Needs mechanical/bag valve mask ventilation.	1 to 10 day
The change of average duration time of apnea episode from baseline in each observation day		1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day
The change of lowest oxygen saturation during apnea episodes from baseline in each observation day		1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day
The proportion of less than 85% oxygen saturation during apnea episodes in each observation day		1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day

Collaborators and Investigators

• Sponsor: Nobelpharma
• Investigators: Principal Investigator: Susumu Itoh, MD, PhD, Kagawa University

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: July 29, 2011
• First Submitted That Met QC Criteria: August 1, 2011
• First Posted (Estimate): August 3, 2011

Study Record Updates

• Last Update Posted (Estimate): October 30, 2013
• Last Update Submitted That Met QC Criteria: October 29, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: apnea; caffeine; prematurity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Apnea; Premature Birth; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine; Caffeine citrate
• Other Study ID Numbers: NPC-11-1