Bronchopulmonary Dysplasia (BPD), Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Infant, Small for Gestational Age, Retinopathy of Prematurity
Conditions
Keywords
NICHD Neonatal Research Network, Pharmacokinetics, Inositol, Very Low Birth Weight (VLBW), Extremely Low Birth Weight (ELBW), Prematurity
Brief 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.
Detailed description
Retinopathy of prematurity (ROP) is an abnormal growth of the blood vessels in the eye that occurs primarily in very premature infants. Eye development occurs normally in the womb; in infants born prematurely, however, the blood vessels must finish developing outside the protective environment of the uterus. Retinopathy of prematurity (also known as retrolental fibroplasia) is a leading cause of blindness and other vision impairments (myopia, strabismus, and amblyopia) in children, both in developed and developing countries. Inositol is a naturally-occurring sugar alcohol produced by the fetus and placenta and is present in high levels in fetal blood throughout pregnancy in humans and other animals. Serum levels fall rapidly after birth, although this fall is moderated in infants who receive breast milk or fortified formula. Two randomized trials have shown that intravenous inositol supplementation in the first week significantly reduced death, bronchopulmonary dysplasia (BPD), and retinopathy. One study of enteral supplements (given orally or via feeding tube) was less convincing, but also supported reduction of retinopathy. This pilot study will evaluate changes in blood and urine inositol levels (half-life pharmacokinetics) of multiple doses of myo-inositol (provided by Abbott Laboratories, Abbott Nutrition Division) given to very low birth weight infants. The premise is that maintaining inositol concentrations similar to those occurring naturally in utero will reduce the rates of retinopathy and bronchopulmonary dysplasia in premature infants. Results from this study will be used to select the dose for a large multi-center trial. In this study, 17 NICHD Neonatal Research Network sites will enroll approximately 96 infants at 12-72 hours of age. Enrolled infants will be randomly assigned to receive either 10mg/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. Inositol will be administered intravenously until babies are feeding normally, at which time the same dose and formulation will be administered enterally (orally or via feeding tube). Concentrations of inositol will be measured in blood, urine, and milk received. Stratification: Recruitment will be stratified by gestational age into infants born at 23 0/7 to 26 6/7 weeks gestational age and infants born at 27 0/7 to 29 6/7 weeks gestational age.
Interventions
5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
DRUGInositol high volume
40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
DRUGPlacebo low volume
Glucose 5% given in volumes equal to that of the comparator drug
Sponsors
National Eye Institute (NEI)
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NICHD Neonatal Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Hours to 72 Hours
Healthy volunteers
Yes
Inclusion criteria
* 23 0/7 to 26 6/7 weeks gestational age (48 infants) or * 27 0/7 to 29 6/7 weeks gestational age (48 infants) * 401 grams birth weight or larger * 12-72 hours of age
Exclusion criteria
* Major congenital and intracranial anomalies * Moribund or not to be provided continued support * Seizures * Suspected renal failure (oliguria \<0.6 cc/kg/hr for \>24 hours or creatinine \>2.5 mg/dL)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Population Pharmacokinetics: V - Volume | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
| Population Pharmacokinetics: Cl - Clearance | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
| Population Pharmacokinetics: R - Endogenous Infusion Rate | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
| Population Pharmacokinetics: k - Elimination Rate (Cl/V) | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
| Population Pharmacokinetics: t1/2 - Half-Life (0.693/k) | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
| Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl) | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
| SD of Residual Error (mg/l) | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death | 8-22 months corrected age. | Moderate or Severe NDI defined as occurrence of any of the following: GMFCS level II or higher (severe is level 4 or 5), Bayley III cognitive composite score \< 85 (severe is \<70), Bayley III motor composite score \< 85 (severe is \<70), unilateral blind or bilateral blind, permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid |
| Number of Participants With Moderate or Severe Cerebral Palsy | 18-22 months corrected age. | Cerebral palsy by severity category (absent/mild/moderate/severe). |
| Number of Participants With Composite Motor Score Less Than 70 | 18-22 months corrected age | This is measured as a scored of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score. Higher scores indicate better performance. |
| Number of Participants With Any Retinopathy of Prematurity (ROP) | 18-22 month corrected age | Any ROP is defined as ROP of any severity that is observed at 18-22 month corrected age |
| Number of Participants With Severe Hearing Impairment | 18-22 months corrected age. | Defined as permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid. |
| Number of Participants With Severe Vision Loss | 18-22 Months Corrected Age | Vision loss as diagnosed by an ophthalmologist as legally blind, and subdivided into ophthalmic origin, or not ophthalmic origin (i.e., cortical blindness is non-ophthalmic in origin and indicates that there is no retinal detachment or other abnormal fundus or ocular finding, except optic atrophy. Such cases will be considered central \[neurologic\] in origin.) |
| Number of Participants With Gross Motor Function Greater Than or Equal to 2 | 18 -22 months corrected age | A Gross Motor Function Classification System (GMFCS) level of at least II (on a scale from level I to V, with I indicating normal gross motor function and higher levels indicating greater impairment). Level II is defined as Infants maintain floor sitting but may need to use their hands for support to maintain balance. Infants creep on their stomach or crawl on hands and knees with reciprocal leg movement. Infants may pull to stand and take steps holding on to furniture.) |
| Number of Participants With Composite Cognitive Score Less Than 70 | 18-22 months corrected age. | This is measured as a score of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score |
| Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death | 18-22 month corrected age | Number of participants with any Retinopathy of Prematurity (ROP) through 18-22 month corrected age or death |
| Number of Participants With Any Ophthalmologic Diagnosis | 18-22 month corrected age | Any ophthalmologic diagnosis at 18-22 month corrected age |
| Number of Participants With Any Ophthalmologic Treatment | 18-22 month corrected age | Any ophthalmologic treatment at 18-22 month corrected age |
| Number of Participants With Any Ophthalmologic Surgical Treatment | 18-22 month corrected age | Any ophthalmologic surgical treatment at 18-22 month corrected age |
| Number of Participants With Any Ophthalmologic Medical Treatment | 18-22 month corrected age | Any ophthalmologic medical treatment at 18-22 month corrected age |
| Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age | 18-22 month corrected age | A composite outcome that measures the occurrence of neurodevelopmental impairment between birth and 18-22 months corrected age. |
Countries
United States
Participant flow
Recruitment details
Infants who were 23(0/7) to 29(6/7) weeks gestational age, weighed at least 400grams, survived \>12 hours, and could receive study drug by 72 hours after birth were screened and enrolled (after meeting eligibility criteria) across 14 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN)
Participants by arm
| Arm | Count |
|---|---|
| Inositol Low Volume 10 mg/kg/day Intravenous inositol 5%
Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 29 |
| Inositol Mid-level Volume 40 mg/kg/day Intravenous inositol 5%
Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 30 |
| Inositol High Volume 80 mg/kg/day Intravenous inositol 5%
Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 28 |
| Placebo Glucose 5% given in volumes equal to that of the comparator drug
Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug | 35 |
| Total | 122 |
Baseline characteristics
| Characteristic | Total | Placebo | Inositol High Volume | Inositol Low Volume | Inositol Mid-level Volume |
|---|---|---|---|---|---|
| Age, Continuous | 26.6 weeks STANDARD_DEVIATION 1.7 | 26.5 weeks STANDARD_DEVIATION 1.6 | 26.7 weeks STANDARD_DEVIATION 1.9 | 26.6 weeks STANDARD_DEVIATION 1.8 | 26.7 weeks STANDARD_DEVIATION 1.8 |
| Antenatal Steroids No | 16 Participants | 3 Participants | 2 Participants | 5 Participants | 6 Participants |
| Antenatal Steroids Yes | 106 Participants | 32 Participants | 26 Participants | 24 Participants | 24 Participants |
| APGAR 1-minute | 4 units on a scale | 3 units on a scale | 5 units on a scale | 5 units on a scale | 3 units on a scale |
| APGAR 5-minute | 7 units on a scale | 7 units on a scale | 7 units on a scale | 8 units on a scale | 7 units on a scale |
| Birth Weight | 909 grams STANDARD_DEVIATION 253 | 884 grams STANDARD_DEVIATION 224 | 921 grams STANDARD_DEVIATION 286 | 897 grams STANDARD_DEVIATION 272 | 939 grams STANDARD_DEVIATION 245 |
| Cesarean Delivery No | 52 Participants | 14 Participants | 14 Participants | 13 Participants | 11 Participants |
| Cesarean Delivery Yes | 70 Participants | 21 Participants | 14 Participants | 16 Participants | 19 Participants |
| Chorioamnionitis No | 106 Participants | 30 Participants | 25 Participants | 25 Participants | 26 Participants |
| Chorioamnionitis Yes | 16 Participants | 5 Participants | 3 Participants | 4 Participants | 4 Participants |
| Early Onset Sepsis No | 121 Participants | 35 Participants | 28 Participants | 29 Participants | 29 Participants |
| Early Onset Sepsis Yes | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 9 Participants | 8 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 26 Participants | 20 Participants | 26 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gestational Age (GA) STRATUM 23-26 Weeks | 64 Participants | 19 Participants | 14 Participants | 15 Participants | 16 Participants |
| Gestational Age (GA) STRATUM 27-29 Weeks | 58 Participants | 16 Participants | 14 Participants | 14 Participants | 14 Participants |
| Head Circumference | 24.3 cm STANDARD_DEVIATION 2.1 | 23.8 cm STANDARD_DEVIATION 2 | 24.6 cm STANDARD_DEVIATION 1.9 | 24.1 cm STANDARD_DEVIATION 2 | 25.1 cm STANDARD_DEVIATION 2.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 58 Participants | 18 Participants | 13 Participants | 15 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 58 Participants | 17 Participants | 15 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Female | 62 Participants | 17 Participants | 16 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Male | 60 Participants | 18 Participants | 12 Participants | 14 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 29 | 5 / 30 | 1 / 28 | 6 / 35 |
| other Total, other adverse events | 24 / 29 | 20 / 30 | 19 / 28 | 24 / 35 |
| serious Total, serious adverse events | 17 / 29 | 20 / 30 | 17 / 28 | 28 / 35 |
Outcome results
Primary
Population Pharmacokinetics: Cl - Clearance
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | Population Pharmacokinetics: Cl - Clearance | 0.0577 (l/kg)/h | Standard Error 0.0061 |
Primary
Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl)
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl) | 41.06 miligrams/liter | Standard Error 1.777 |
Primary
Population Pharmacokinetics: k - Elimination Rate (Cl/V)
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | Population Pharmacokinetics: k - Elimination Rate (Cl/V) | 0.0878 liter/hour | Standard Error 0.0137 |
Primary
Population Pharmacokinetics: R - Endogenous Infusion Rate
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | Population Pharmacokinetics: R - Endogenous Infusion Rate | 2.369 (mg/kg)/h | Standard Error 0.3151 |
Primary
Population Pharmacokinetics: t1/2 - Half-Life (0.693/k)
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | Population Pharmacokinetics: t1/2 - Half-Life (0.693/k) | 7.90 hour | Standard Error 1.229 |
Primary
Population Pharmacokinetics: V - Volume
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | Population Pharmacokinetics: V - Volume | 0.6572 l/kg | Standard Error 0.0707 |
Primary
SD of Residual Error (mg/l)
Time frame: 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.
Population: All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PK Population | SD of Residual Error (mg/l) | 24.77 mg/l | Standard Error 0.971 |
Secondary
Number of Participants With Any Ophthalmologic Diagnosis
Any ophthalmologic diagnosis at 18-22 month corrected age
Time frame: 18-22 month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Any Ophthalmologic Diagnosis | 9 Participants |
| Inositol Mid-level Volume | Number of Participants With Any Ophthalmologic Diagnosis | 6 Participants |
| Inositol High Volume | Number of Participants With Any Ophthalmologic Diagnosis | 10 Participants |
| Placebo | Number of Participants With Any Ophthalmologic Diagnosis | 5 Participants |
Secondary
Number of Participants With Any Ophthalmologic Medical Treatment
Any ophthalmologic medical treatment at 18-22 month corrected age
Time frame: 18-22 month corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Any Ophthalmologic Medical Treatment | 2 Participants |
| Inositol Mid-level Volume | Number of Participants With Any Ophthalmologic Medical Treatment | 1 Participants |
| Inositol High Volume | Number of Participants With Any Ophthalmologic Medical Treatment | 1 Participants |
| Placebo | Number of Participants With Any Ophthalmologic Medical Treatment | 2 Participants |
Secondary
Number of Participants With Any Ophthalmologic Surgical Treatment
Any ophthalmologic surgical treatment at 18-22 month corrected age
Time frame: 18-22 month corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Any Ophthalmologic Surgical Treatment | 3 Participants |
| Inositol Mid-level Volume | Number of Participants With Any Ophthalmologic Surgical Treatment | 4 Participants |
| Inositol High Volume | Number of Participants With Any Ophthalmologic Surgical Treatment | 0 Participants |
| Placebo | Number of Participants With Any Ophthalmologic Surgical Treatment | 4 Participants |
Secondary
Number of Participants With Any Ophthalmologic Treatment
Any ophthalmologic treatment at 18-22 month corrected age
Time frame: 18-22 month corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Any Ophthalmologic Treatment | 4 Participants |
| Inositol Mid-level Volume | Number of Participants With Any Ophthalmologic Treatment | 4 Participants |
| Inositol High Volume | Number of Participants With Any Ophthalmologic Treatment | 2 Participants |
| Placebo | Number of Participants With Any Ophthalmologic Treatment | 5 Participants |
Secondary
Number of Participants With Any Retinopathy of Prematurity (ROP)
Any ROP is defined as ROP of any severity that is observed at 18-22 month corrected age
Time frame: 18-22 month corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Any Retinopathy of Prematurity (ROP) | 11 Participants |
| Inositol Mid-level Volume | Number of Participants With Any Retinopathy of Prematurity (ROP) | 11 Participants |
| Inositol High Volume | Number of Participants With Any Retinopathy of Prematurity (ROP) | 14 Participants |
| Placebo | Number of Participants With Any Retinopathy of Prematurity (ROP) | 12 Participants |
Secondary
Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death
Number of participants with any Retinopathy of Prematurity (ROP) through 18-22 month corrected age or death
Time frame: 18-22 month corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death | 13 Participants |
| Inositol Mid-level Volume | Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death | 17 Participants |
| Inositol High Volume | Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death | 15 Participants |
| Placebo | Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death | 18 Participants |
Secondary
Number of Participants With Composite Cognitive Score Less Than 70
This is measured as a score of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score
Time frame: 18-22 months corrected age.
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Composite Cognitive Score Less Than 70 | 0 Participants |
| Inositol Mid-level Volume | Number of Participants With Composite Cognitive Score Less Than 70 | 1 Participants |
| Inositol High Volume | Number of Participants With Composite Cognitive Score Less Than 70 | 1 Participants |
| Placebo | Number of Participants With Composite Cognitive Score Less Than 70 | 2 Participants |
Secondary
Number of Participants With Composite Motor Score Less Than 70
This is measured as a scored of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score. Higher scores indicate better performance.
Time frame: 18-22 months corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Composite Motor Score Less Than 70 | 1 Participants |
| Inositol Mid-level Volume | Number of Participants With Composite Motor Score Less Than 70 | 1 Participants |
| Inositol High Volume | Number of Participants With Composite Motor Score Less Than 70 | 2 Participants |
| Placebo | Number of Participants With Composite Motor Score Less Than 70 | 6 Participants |
Secondary
Number of Participants With Gross Motor Function Greater Than or Equal to 2
A Gross Motor Function Classification System (GMFCS) level of at least II (on a scale from level I to V, with I indicating normal gross motor function and higher levels indicating greater impairment). Level II is defined as Infants maintain floor sitting but may need to use their hands for support to maintain balance. Infants creep on their stomach or crawl on hands and knees with reciprocal leg movement. Infants may pull to stand and take steps holding on to furniture.)
Time frame: 18 -22 months corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Gross Motor Function Greater Than or Equal to 2 | 0 Participants |
| Inositol Mid-level Volume | Number of Participants With Gross Motor Function Greater Than or Equal to 2 | 2 Participants |
| Inositol High Volume | Number of Participants With Gross Motor Function Greater Than or Equal to 2 | 3 Participants |
| Placebo | Number of Participants With Gross Motor Function Greater Than or Equal to 2 | 4 Participants |
Secondary
Number of Participants With Moderate or Severe Cerebral Palsy
Cerebral palsy by severity category (absent/mild/moderate/severe).
Time frame: 18-22 months corrected age.
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Moderate or Severe Cerebral Palsy | 0 Participants |
| Inositol Mid-level Volume | Number of Participants With Moderate or Severe Cerebral Palsy | 1 Participants |
| Inositol High Volume | Number of Participants With Moderate or Severe Cerebral Palsy | 1 Participants |
| Placebo | Number of Participants With Moderate or Severe Cerebral Palsy | 2 Participants |
Secondary
Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age
A composite outcome that measures the occurrence of neurodevelopmental impairment between birth and 18-22 months corrected age.
Time frame: 18-22 month corrected age
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age | 8 Participants |
| Inositol Mid-level Volume | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age | 9 Participants |
| Inositol High Volume | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age | 11 Participants |
| Placebo | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age | 13 Participants |
Secondary
Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death
Moderate or Severe NDI defined as occurrence of any of the following: GMFCS level II or higher (severe is level 4 or 5), Bayley III cognitive composite score \< 85 (severe is \<70), Bayley III motor composite score \< 85 (severe is \<70), unilateral blind or bilateral blind, permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid
Time frame: 8-22 months corrected age.
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death | 10 Participants |
| Inositol Mid-level Volume | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death | 15 Participants |
| Inositol High Volume | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death | 13 Participants |
| Placebo | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death | 20 Participants |
Secondary
Number of Participants With Severe Hearing Impairment
Defined as permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid.
Time frame: 18-22 months corrected age.
Population: Intent to Treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Severe Hearing Impairment | 0 Participants |
| Inositol Mid-level Volume | Number of Participants With Severe Hearing Impairment | 0 Participants |
| Inositol High Volume | Number of Participants With Severe Hearing Impairment | 0 Participants |
| Placebo | Number of Participants With Severe Hearing Impairment | 0 Participants |
Secondary
Number of Participants With Severe Vision Loss
Vision loss as diagnosed by an ophthalmologist as legally blind, and subdivided into ophthalmic origin, or not ophthalmic origin (i.e., cortical blindness is non-ophthalmic in origin and indicates that there is no retinal detachment or other abnormal fundus or ocular finding, except optic atrophy. Such cases will be considered central \[neurologic\] in origin.)
Time frame: 18-22 Months Corrected Age
Population: Intent to Treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PK Population | Number of Participants With Severe Vision Loss | 0 Participants |
| Inositol Mid-level Volume | Number of Participants With Severe Vision Loss | 0 Participants |
| Inositol High Volume | Number of Participants With Severe Vision Loss | 0 Participants |
| Placebo | Number of Participants With Severe Vision Loss | 0 Participants |