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Safety and Efficacy of Caffeine Citrate in Premature Infants NICHD-2014-CAF01

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Safety and Efficacy of Caffeine Citrate in Premature Infants NICHD-2014-CAF01 NICHD-2014-CAF01 – CAFFEINE Version 2.0 IND # N/A 03AUG2015 ____________________________________________________________________________________________ Pediatric Trials Network Safety and Efficacy of Caffeine Citrate in Premature Infants NICHD-2014-CAF01 Funding Sponsor: The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Funding Mechanism: Task Order Protocol Number: NICHD-2014-CAF01 Protocol Date: 03AUG2015 Protocol Version: 2.0 IND Number: N/A Principal Investigator (IND Sponsor): P. Brian Smith, MD, MPH, MHS Professor of Pediatrics Duke University Medical Center 2400 Pratt St. Durham, NC 27705 Redacted ____________________________________________________________________________________________ NICHD-2014-CAF01 – CAFFEINE Version 2.0 IND # N/A 03AUG2015 ____________________________________________________________________________________________ Statement of Compliance This trial will be conducted in compliance with the protocol, International Conference on Harmonization (ICH) guideline E6: Good Clinical Practice (GCP): Consolidated Guideline, and the applicable regulatory requirements from the United States Code of Federal Regulations (CFR), including 45 CFR 46 (human subjects protection), 21 CFR 312 (Investigational New Drug), 21 CFR part 50 (informed consent), and 21 CFR part 56 (institutional review board [IRB]). All individuals responsible for the design and/or conduct of this study have completed Human Subjects Protection Training and are qualified to be conducting this research. ____________________________________________________________________________________________ i NICHD-2014-CAF01 – CAFFEINE Version 2.0 IND # N/A 03AUG2015 ____________________________________________________________________________________________ SITE PRINCIPAL INVESTIGATOR STATEMENT I have read the protocol, including all appendices, and the product label, and I agree that it contains all necessary details for my staff and me to conduct this study as described. I will personally oversee the conduct of this study as outlined herein and will make a reasonable effort to complete the study within the time designated. I agree to make all reasonable efforts to adhere to the attached protocol. I will provide all study personnel under my supervision with copies of the protocol and access to all information provided by the sponsor or the sponsor’s representative. I will discuss this material with study personnel to ensure that they are fully informed about the efficacy and safety parameters and the conduct of the study in general. I am aware that, before beginning this study, the institutional review board responsible for such matters must approve this protocol in the clinical facility where it will be conducted. I agree to provide all subjects with informed consent forms, as required by government and International Conference on Harmonization regulations. I further agree to report to the sponsor or its representative any adverse events in accordance with the terms of this protocol and the U.S. Code of Federal Regulations, Title 21, part 312.64. Principal Investigator Name (Print) Signature Date ____________________________________________________________________________________________ ii NICHD-2014-CAF01 – CAFFEINE Version 2.0 IND # N/A 03AUG2015 ____________________________________________________________________________________________ STUDY PRINCIPAL INVESTIGATOR / IND SPONSOR SIGNATURE The signature below documents the review and approval of this protocol and the attachments (e.g., product label), and provides the necessary assurances that this clinical study will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality and according to local legal and regulatory requirements and to the principles outlined in applicable U.S. federal regulations and ICH guidelines. P. Brian Smith, MD, MPH, MHS Pediatric Trials Network Study Principal Investigator Name Signature Date ____________________________________________________________________________________________ iii NICHD-2014-CAF01 – CAFFEINE Version 2.0 IND # N/A 03AUG2015 ____________________________________________________________________________________________ Table of Contents page Statement of Compliance ............................................................................................................. i Signature Pages ......................................................................................................................... ii List of Abbreviations ................................................................................................................... vi Protocol Synopsis ................................................................................................................. …viii 1 Key Roles ...........................................................................................................................1 2 Background Information and Scientific Rationale................................................................ 2 2.1 Background Information ..........................................................................................2 2.2 Apnea of Prematurity ..............................................................................................2 2.3 Caffeine ..................................................................................................................2 2.3.1 Safety ..........................................................................................................3 2.3.2 Pharmacokinetics/Pharmacodynamics ........................................................ 4 2.3.3 The Caffeine for Apnea of Prematurity Trial (CAP)31 ................................... 5 2.3.4 Caffeine and NEC .......................................................................................6 2.3.5 Caffeine and BPD .......................................................................................6 2.4 Scientific Rationale ................................................................................................. 6 2.5 Potential Risks and Benefits ................................................................................... 6 2.5.1 Potential Risks ............................................................................................ 6 2.5.2 Potential Benefits ........................................................................................7 3 Study Design ......................................................................................................................8 4 Study Population ................................................................................................................9 4.1 Selection of the Study Population ........................................................................... 9 4.1.1 Objective 1: Safety ......................................................................................9 4.1.2 Objective 2: Efficacy .................................................................................... 9 4.1.3 Objective 3: Exposure-response Relationship ............................................. 9 4.2 Inclusion/Exclusion Criteria ..................................................................................... 9 5 Study procedures ............................................................................................................. 11 5.1 Pediatrix Clinical Data Warehouse Database ........................................................ 11 5.2 Electronic Health Record Data Extraction ............................................................. 12 5.3 PROP ................................................................................................................... 13 5.4 Review of Published Data from the CAP Trial ....................................................... 14 5.5 Enrollment/Baseline .............................................................................................. 14 5.6 Follow-up .............................................................................................................. 14 5.7 Final Study Visit .................................................................................................... 14 6 Study Product Description ................................................................................................ 15 6.1 Concomitant Medications/Treatments ................................................................... 15 7 Assessment of Safety ....................................................................................................... 16 8 Clinical Monitoring ............................................................................................................ 17 9 Statistical Considerations ................................................................................................. 18 9.1 Sample Size ......................................................................................................... 18 9.1.1 Pediatrix Clinical Data Warehouse Database Review ................................ 18 9.1.2 Electronic Health Record Data Extraction .................................................. 18 9.1.3 PROP ........................................................................................................ 18 9.1.4 Review of Published Data from the CAP Trial ........................................... 18 9.2 Planned Interim Analyses (if applicable) ............................................................... 18 9.3 Analysis Plan .......................................................................................................
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