Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2)

Summary

This pilot study is a randomized, placebo-controlled, clinical trial to measure changes in blood and urine levels of inositol in premature infants at high risk for retinopathy of prematurity (ROP) following repeated doses of inositol. Based on previous studies, the premise is that maintaining inositol concentrations similar to those occurring naturally in utero will reduce the rates of ROP and bronchopulmonary dysplasia in premature infants. The objective is to evaluate pharmacokinetics, safety, and clinical outcomes of multiple doses of three different dose amounts of myo-inositol (provided by Abbott Laboratories) in very low birth weight premature infants. This study will enroll an estimated 96 infants at 17 NICHD Neonatal Research Network sites. Infants will be randomly assigned to receive either 10 mg/kg of 5% inositol, 40 mg/kg of 5% inositol, 80 mg/kg of 5% inositol, or 5% glucose given in the same volumes and timings as the inositol dosage to maintain masking. Enrollees will receive their assigned dose or placebo daily, starting within 72 hours of birth, and continuing until they reach 34 weeks post-menstrual age, 10 weeks chronologic age, or until the time of hospital discharge, whichever occurs first. The study drug will be administered first intravenously; as the infants progress to full feeding, the drug will be given enterally (orally or via feeding tube). Enrollees will be seen for a follow-up examination at 18-22 months corrected age. This pilot study is in preparation for a future Phase III multi-center randomized controlled trial.

Conditions

• Infant, Newborn
• Infant, Low Birth Weight
• Infant, Small for Gestational Age
• Infant, Premature
• Retinopathy of Prematurity
• Bronchopulmonary Dysplasia (BPD)

Interventions

DRUG

Inositol lower volume

5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes

DRUG

Inositol mid-level volume

20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes

DRUG

Inositol high volume

40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes

DRUG

Placebo low volume

Glucose 5% given in volumes equal to that of the comparator drug

Sponsors & Collaborators

• National Eye Institute (NEI)

  collaborator NIH

• National Center for Research Resources (NCRR)

  collaborator NIH

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• NICHD Neonatal Research Network

  lead NETWORK

Principal Investigators

• Abbot R. Laptook, MD · Brown University, Women & Infants Hospital of Rhode Island

• Michele C. Walsh, MD MS · Case Western Reserve University, Rainbow Babies and Children's Hospital

• Ronald N. Goldberg, MD · Duke University

• Barbara J. Stoll, MD · Emory University

• Brenda B. Poindexter, MD MS · Indiana University

• Abhik Das, PhD · RTI International

• Krisa P. Van Meurs, MD · Stanford University

• Ivan D. Frantz III, MD · Tufts Medical Center

• Kurt Schibler, MD · Children's Hospital Medical Center, Cincinnati

• Waldemar A. Carlo, MD · University of Alabama at Birmingham

• Edward F Bell, MD · University of Iowa

• Kristi L. Watterberg, MD · University of New Mexico

• Dale L. Phelps, MD · University of Rochester

• Pablo J. Sanchez, MD · University of Texas, Southwestern Medical Center at Dallas

• Kathleen A. Kennedy, MD MPH · The University of Texas Health Science Center, Houston

• Roger G. Faix, MD · University of Utah

• Seetha Shankaran, MD · Wayne State University

• Richard A. Ehrenkranz, MD · Yale University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

12 Hours

Max Age

72 Hours

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2010-01-31

Primary Completion

2011-05-31

Completion

2013-09-30

FDA Drug

Yes

Countries

• United States

Study Locations