Trial Outcomes & Findings for Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2) (NCT NCT01030575)

NCT ID: NCT01030575

Last Updated: 2022-06-14

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 125 participants
• Primary outcome timeframe: 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.
• Results posted on: 2022-06-14

Participant Flow

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)

Participant milestones

Measure	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	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	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	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
Overall Study STARTED	29	30	28	35
Overall Study COMPLETED	29	30	28	35
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Inositol Low Volume n=29 Participants 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol Mid-level Volume n=30 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=28 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=35 Participants 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	Total n=122 Participants Total of all reporting groups
Age, Continuous	26.6 weeks STANDARD_DEVIATION 1.8 • n=5 Participants	26.7 weeks STANDARD_DEVIATION 1.8 • n=7 Participants	26.7 weeks STANDARD_DEVIATION 1.9 • n=5 Participants	26.5 weeks STANDARD_DEVIATION 1.6 • n=4 Participants	26.6 weeks STANDARD_DEVIATION 1.7 • n=21 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	17 Participants n=4 Participants	62 Participants n=21 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	18 Participants n=4 Participants	60 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	27 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	23 Participants n=7 Participants	20 Participants n=5 Participants	26 Participants n=4 Participants	95 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	18 Participants n=4 Participants	58 Participants n=21 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	17 Participants n=7 Participants	15 Participants n=5 Participants	17 Participants n=4 Participants	58 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Head Circumference	24.1 cm STANDARD_DEVIATION 2.0 • n=5 Participants	25.1 cm STANDARD_DEVIATION 2.5 • n=7 Participants	24.6 cm STANDARD_DEVIATION 1.9 • n=5 Participants	23.8 cm STANDARD_DEVIATION 2.0 • n=4 Participants	24.3 cm STANDARD_DEVIATION 2.1 • n=21 Participants
Birth Weight	897 grams STANDARD_DEVIATION 272 • n=5 Participants	939 grams STANDARD_DEVIATION 245 • n=7 Participants	921 grams STANDARD_DEVIATION 286 • n=5 Participants	884 grams STANDARD_DEVIATION 224 • n=4 Participants	909 grams STANDARD_DEVIATION 253 • n=21 Participants
Antenatal Steroids Yes	24 Participants n=5 Participants	24 Participants n=7 Participants	26 Participants n=5 Participants	32 Participants n=4 Participants	106 Participants n=21 Participants
Antenatal Steroids No	5 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	16 Participants n=21 Participants
Early Onset Sepsis Yes	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Early Onset Sepsis No	29 Participants n=5 Participants	29 Participants n=7 Participants	28 Participants n=5 Participants	35 Participants n=4 Participants	121 Participants n=21 Participants
Cesarean Delivery Yes	16 Participants n=5 Participants	19 Participants n=7 Participants	14 Participants n=5 Participants	21 Participants n=4 Participants	70 Participants n=21 Participants
Cesarean Delivery No	13 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants	14 Participants n=4 Participants	52 Participants n=21 Participants
Chorioamnionitis Yes	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	16 Participants n=21 Participants
Chorioamnionitis No	25 Participants n=5 Participants	26 Participants n=7 Participants	25 Participants n=5 Participants	30 Participants n=4 Participants	106 Participants n=21 Participants
APGAR 1-minute	5 units on a scale n=5 Participants	3 units on a scale n=7 Participants	5 units on a scale n=5 Participants	3 units on a scale n=4 Participants	4 units on a scale n=21 Participants
APGAR 5-minute	8 units on a scale n=5 Participants	7 units on a scale n=7 Participants	7 units on a scale n=5 Participants	7 units on a scale n=4 Participants	7 units on a scale n=21 Participants
Gestational Age (GA) STRATUM 23-26 Weeks	15 Participants n=5 Participants	16 Participants n=7 Participants	14 Participants n=5 Participants	19 Participants n=4 Participants	64 Participants n=21 Participants
Gestational Age (GA) STRATUM 27-29 Weeks	14 Participants n=5 Participants	14 Participants n=7 Participants	14 Participants n=5 Participants	16 Participants n=4 Participants	58 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
Population Pharmacokinetics: V - Volume	0.6572 l/kg Standard Error 0.0707	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
Population Pharmacokinetics: Cl - Clearance	0.0577 (l/kg)/h Standard Error 0.0061	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
Population Pharmacokinetics: R - Endogenous Infusion Rate	2.369 (mg/kg)/h Standard Error 0.3151	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
Population Pharmacokinetics: k - Elimination Rate (Cl/V)	0.0878 liter/hour Standard Error 0.0137	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
Population Pharmacokinetics: t1/2 - Half-Life (0.693/k)	7.90 hour Standard Error 1.229	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl)	41.06 miligrams/liter Standard Error 1.777	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	PK Population n=122 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	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	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	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
SD of Residual Error (mg/l)	24.77 mg/l Standard Error 0.971	—	—	—

SECONDARY outcome

Timeframe: 18-22 month corrected age

Population: ITT

Any ROP is defined as ROP of any severity that is observed at 18-22 month corrected age

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=23 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=25 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=24 Participants 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
Number of Participants With Any Retinopathy of Prematurity (ROP)	11 Participants	11 Participants	14 Participants	12 Participants

SECONDARY outcome

Timeframe: 18-22 month corrected age

Population: ITT

Number of participants with any Retinopathy of Prematurity (ROP) through 18-22 month corrected age or death

Outcome measures

Measure	PK Population n=26 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=29 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=26 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=30 Participants 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
Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death	13 Participants	17 Participants	15 Participants	18 Participants

SECONDARY outcome

Timeframe: 18-22 month corrected age

Any ophthalmologic diagnosis at 18-22 month corrected age

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=21 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=21 Participants 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
Number of Participants With Any Ophthalmologic Diagnosis	9 Participants	6 Participants	10 Participants	5 Participants

SECONDARY outcome

Timeframe: 18-22 month corrected age

Population: ITT

Any ophthalmologic treatment at 18-22 month corrected age

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=21 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=21 Participants 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
Number of Participants With Any Ophthalmologic Treatment	4 Participants	4 Participants	2 Participants	5 Participants

SECONDARY outcome

Timeframe: 18-22 month corrected age

Population: ITT

Any ophthalmologic surgical treatment at 18-22 month corrected age

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=21 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=21 Participants 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
Number of Participants With Any Ophthalmologic Surgical Treatment	3 Participants	4 Participants	0 Participants	4 Participants

SECONDARY outcome

Timeframe: 18-22 month corrected age

Population: ITT

Any ophthalmologic medical treatment at 18-22 month corrected age

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=21 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=21 Participants 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
Number of Participants With Any Ophthalmologic Medical Treatment	2 Participants	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 18-22 month corrected age

Population: ITT

A composite outcome that measures the occurrence of neurodevelopmental impairment between birth and 18-22 months corrected age.

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=23 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=27 Participants 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
Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age	8 Participants	9 Participants	11 Participants	13 Participants

SECONDARY outcome

Timeframe: 8-22 months corrected age.

Population: ITT

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

Outcome measures

Measure	PK Population n=26 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=29 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=24 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=34 Participants 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
Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death	10 Participants	15 Participants	13 Participants	20 Participants

SECONDARY outcome

Timeframe: 18-22 months corrected age.

Population: ITT

Cerebral palsy by severity category (absent/mild/moderate/severe).

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=24 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=23 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=27 Participants 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
Number of Participants With Moderate or Severe Cerebral Palsy	0 Participants	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 18-22 months corrected age

Population: ITT

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.

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=22 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=25 Participants 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
Number of Participants With Composite Motor Score Less Than 70	1 Participants	1 Participants	2 Participants	6 Participants

SECONDARY outcome

Timeframe: 18-22 months corrected age.

Population: ITT

This is measured as a score of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=23 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=22 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=26 Participants 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
Number of Participants With Composite Cognitive Score Less Than 70	0 Participants	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 18-22 months corrected age.

Population: Intent to Treat (ITT)

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.

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=24 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=23 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=27 Participants 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
Number of Participants With Severe Hearing Impairment	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 18-22 Months Corrected Age

Population: Intent to Treat (ITT)

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.)

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=24 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=23 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=27 Participants 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
Number of Participants With Severe Vision Loss	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 18 -22 months corrected age

Population: ITT

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.)

Outcome measures

Measure	PK Population n=24 Participants A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model.	Inositol Mid-level Volume n=24 Participants 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=23 Participants 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=27 Participants 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
Number of Participants With Gross Motor Function Greater Than or Equal to 2	0 Participants	2 Participants	3 Participants	4 Participants

Adverse Events

Inositol Low Volume

Serious events: 17 serious events

Other events: 24 other events

Deaths: 2 deaths

Inositol Mid-level Volume

Serious events: 20 serious events

Other events: 20 other events

Deaths: 5 deaths

Inositol High Volume

Serious events: 17 serious events

Other events: 19 other events

Deaths: 1 deaths

Placebo

Serious events: 28 serious events

Other events: 24 other events

Deaths: 6 deaths

Serious adverse events

Measure	Inositol Low Volume n=29 participants at risk 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol Mid-level Volume n=30 participants at risk 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=28 participants at risk 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=35 participants at risk 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
Cardiac disorders Poor perfusion or hypotension	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.0% 3/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	21.4% 6/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	22.9% 8/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Delayed gastric emptying	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	23.3% 7/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	17.9% 5/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	20.0% 7/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Anemia	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	20.0% 6/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	25.0% 7/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	37.1% 13/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Thrombocytosis	13.8% 4/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	7.1% 2/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 5/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Metabolism and nutrition disorders Hyperglycemia	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	11.4% 4/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Other	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Respiratory, thoracic and mediastinal disorders Apnea	13.8% 4/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	20.0% 6/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	32.1% 9/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	17.1% 6/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Other	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	7.1% 2/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	11.4% 4/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.

Other adverse events

Measure	Inositol Low Volume n=29 participants at risk 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol Mid-level Volume n=30 participants at risk 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Inositol High Volume n=28 participants at risk 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes	Placebo n=35 participants at risk 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
Cardiac disorders Congestive heart failure	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Cardiac disorders Hypertension	13.8% 4/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.0% 3/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 5/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Cardiac disorders Poor perfusion or hypotension	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	6.7% 2/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.7% 3/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	8.6% 3/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Cardiac disorders Tachycardia	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Cardiac disorders Other	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Delayed gastric emptying	34.5% 10/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	26.7% 8/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	25.0% 7/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	28.6% 10/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Direct (conjugated) hyperbilirubinemia	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	8.6% 3/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Elevated liver enzymes	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Emesis	6.9% 2/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Gastrointestinal disorders Other	6.9% 2/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
General disorders Other	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Anemia	6.9% 2/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	23.3% 7/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	11.4% 4/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Neutropenia	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	6.7% 2/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.7% 3/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Thrombocytopenia	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	6.7% 2/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Thrombocytosis	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.0% 3/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	17.1% 6/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Blood and lymphatic system disorders Other	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Infections and infestations Infection	6.9% 2/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Metabolism and nutrition disorders Hyperglycemia	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	13.3% 4/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	7.1% 2/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 5/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Metabolism and nutrition disorders Hypoglycemia	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	6.7% 2/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Metabolism and nutrition disorders Other	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	11.4% 4/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Respiratory, thoracic and mediastinal disorders Apnea	10.3% 3/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	13.3% 4/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 5/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Respiratory, thoracic and mediastinal disorders Increased fraction of inspired oxygen (FiO2)	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	7.1% 2/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Respiratory, thoracic and mediastinal disorders Other	6.9% 2/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	7.1% 2/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Diuresis	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	16.7% 5/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.7% 3/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	22.9% 8/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Elevated creatinine	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	6.7% 2/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	10.7% 3/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Elevated potassium	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	6.7% 2/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Hematuria	6.9% 2/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	5.7% 2/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Oliguria	17.2% 5/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	14.3% 4/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	8.6% 3/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Renal and urinary disorders Proteinuria	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	8.6% 3/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Skin and subcutaneous tissue disorders Rash	3.4% 1/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
Skin and subcutaneous tissue disorders Skin breakdown	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.3% 1/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
General disorders Fever	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	2.9% 1/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.
General disorders Hypothermia	0.00% 0/29 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/30 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	3.6% 1/28 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.	0.00% 0/35 • From start of study drug treatment through 7-days post last dose of study drug Note that the primary trial publication mislabels serious adverse events as severe adverse events.

Additional Information

Dr. Abhik Das

RTI International

Phone: 301-770-8214

Email: adas@rti.org

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators must adhere to the Neonatal Research Network Publication policies.
• Publication restrictions are in place

Restriction type: OTHER