Safety and Nutritional Adequacy of a New Infant Formula in Healthy Term Infants

Study Overview
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Brief Summary
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This study is a multicenter, double-blind, randomized, controlled, parallel-designed, prospective study and is intended to evaluate the nutritional adequacy and tolerance of a new study formula compared with a concurrent control formula. Approximately 450 infants will be enrolled from approximately 3 China sites. Of these infants, approximately 300 will be randomized 1:1 to receive an investigational formula or a control formula for 16weeks of feeding. The remaining approximately 150 infants will be enrolled as a breastfeeding reference group. The primary outcome measure is the rate of weight gain in g/day between baseline and 16 weeks in the test group compared to control formula group. Participants will have the option of providing stool samples at 8 weeks and 16 weeks for analysis of microbiota and metabolomics. The study period will be 16 weeks, and all infants in the 2 formula groups will receive formula free of charge for 6 months.

Detailed Description
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Primary Objective 1) Compare the rate of weight gain (in g/day) between infants receiving an investigational formula and infants receiving a control formula between at baseline (B), B+2 weeks, B+4 weeks, B+8 weeks, B+12 weeks, and B+16 weeks. Secondary Objectives Compare rate of change in length (mm/day) among infants receiving an investigational formula, infants receiving a control formula, and breastfeeding infants at baseline (B), B+2 weeks, B+4 weeks, B+8 weeks, B+12 weeks, and B+16 weeks. Compare rate of change in head circumference (mm/day) among infants receiving an investigational formula, infants receiving a control formula and breastfeeding infants at baseline (B), B+2 weeks, B+4 weeks, B+8 weeks, B+12 weeks, and B+16 weeks. Evaluate and compare achieved body weight, length, and head circumference at each visit and after 16 weeks. Evaluate plotted raw growth data on World Health Organization standard growth charts.1 Compare the types and incidence of adverse events among infants receiving an investigational formula, infants receiving a control formula, and breastfeeding infants. Compare average daily intake of formula between infants receiving an investigational formula and infants receiving a control formula. Compare parents' and physician's assessment of formula tolerance among infants receiving an investigational formula, infants receiving a control formula, and breastfeeding infants. Compare counts of Bifidobacteria and Lactobacillus species in stools of infants receiving an investigational formula, infants receiving a control formula, and breastfeeding infants. Compare stool short-chain fatty acid metabolites (including total SCFAs, acetic, propionic, n-butyric, iso-butyric and n-valeric acids, L-lactic acid and D-lactic acid, etc) among infants receiving an investigational formula, infants receiving a control formula, and breastfeeding infants.

Official Title
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Randomized, Double-blind, Parallel, Controlled Study to Evaluate the Safety and Nutritional Adequacy of a New Infant Formula in Healthy Term Infants

Conditions
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Child Development

Intervention / Treatment
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* Dietary Supplement: Oral feeding of Feihe Stage 1 infant formula
* Dietary Supplement: Oral feeding of control Stage 1 formula
* Dietary Supplement: Breast feeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 10-14 days of age at enrolment and randomization, inclusive (day of birth is considered day 0) Plan to exclusively formula feed (formula groups) OR exclusively feed human milk (breastfeeding group) Healthy singleton birth Gestational age of 37-42 completed weeks (37 weeks 0 days through 42 weeks 6 days) Birth weight of 2490g to 4200g Signed informed consent obtained for infant's and mother's participation in the study Exclusion Criteria: History of underlying metabolic or chronic disease; congenital malformation; or any other condition which, in the opinion of the Investigator, is likely to interfere with: the ability of the infant to ingest food, the normal growth and development of the infant, or the evaluation of the infant Evidence of feeding difficulties or formula intolerance, such as vomiting or poor intake, at time of randomization (at investigator discretion) Known allergy to cow's milk protein or a well-documented family history of allergy to cow's milk protein Weight at randomization is <90% of birth weight [(weight at Visit 1÷birth weight) x 100 <90%] Immunocompromised (according to a doctor's diagnosis of immunodeficiency such as Combined Immunodeficiencies, DiGeorge Syndrome, Wiskott-Aldrich Syndrome, Severe Congenital Neutropenia and Secondary Immunodeficiencies linked to HIV infection, Down Syndrome or others) Known head/brain disease/injury such as microcephaly, macrocephaly or others. Enrollment in another interventional clinical research study while participating in this study

Ages Eligible for Study
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Minimum Age: 10 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Formula<br>Feihe Stage 1 infant formula | Dietary Supplement: Oral feeding of Feihe Stage 1 infant formula<br>* Oral feeding of Feihe Stage 1 infant formula for 16 weeks<br>|
| Active Comparator: Control formula<br>A commercially available product with comparable composition but does not contain sn-2 palmitate enriched vegetable oil as an ingredient (regular vegetable oil is used) | Dietary Supplement: Oral feeding of control Stage 1 formula<br>* Oral feeding of control Stage 1 formula for 16 weeks (A commercially available product with comparable composition but does not contain sn-2 palmitate enriched vegetable oil as an ingredient (regular vegetable oil is used))<br>|
| Other: Breast feeding<br>Breast fed of human milk | Dietary Supplement: Breast feeding<br>* Breast feeding of human milk for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of change in body weight (grams/day) from baseline | Rate of change in body weight (grams/day) between baseline and B+2 weeks, B+4 weeks, B+8 weeks, B+12 weeks, and B+16 weeks. | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of change in body length (mm/day) from baseline | Rate of change in length (mm/day) measured between baseline (B) and B+2 weeks, B+4 weeks, B+8 weeks, B+12 weeks, and B+16 weeks. | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 
| Rate of change in head circumference (mm/day) from baseline | Rate of change in head circumference (mm/day) measured between baseline (B) and B+2 weeks, B+4 weeks, B+8 weeks, B+12 weeks, and B+16 weeks. | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 
| Achieved body weight | Achieved body weight (grams) at each study visit | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 
| Achieved body length | Achieved body length (cm) at each study visit | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 
| Achieved head circumference | Achieved head circumference (cm) at each study visit | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 
| Percentages of infants in each group who are <10th percentile in weight for age. | Percentages of infants in each group who are <10th percentile in weight for age. | 16 weeks | 
| Percentages of infants in each group who are <10th percentile in length for age. | Percentages of infants in each group who are <10th percentile in length for age. | 16 weeks | 
| Percentages of infants in each group who are <10th percentile in head circumference for age. | Percentages of infants in each group who are <10th percentile in head circumference for age. | 16 weeks | 
| Adverse events rate | Number and percentages of infants in each group experiencing any adverse events and any serious adverse events | 16 weeks | 
| Average daily formula intake | Average daily formula intake volume based on 3-day records kept by parents or care-givers prior to each study visit. | 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks | 
| Percentage of fussiness | Percentages of parents in each group reporting fussiness | 16 weeks | 
| Percentage of colic | Percentages of parents in each group reporting colic | 16 weeks | 
| Percentage of patterns | Percentages of parents in each group reporting sleeping patterns | 16 weeks | 
| Percentage of cramps | Percentages of parents in each group reporting cramps | 16 weeks | 
| Percentage of regurgitation | Percentages of parents in each group reporting regurgitation | 16 weeks | 
| Stool characteristics | Score of stool characteristics | 16 weeks | 
| Percentage of respiratory manifestations | Percentages of parents in each group reporting respiratory manifestations | 16 weeks | 
| Percentage of dermatologic manifestations | Percentages of parents in each group reporting dermatologic manifestations | 16 weeks | 
| Fecal Bifidobacteria counts | Total fecal Bifidobacteria counts (mean log10 counts / g wet-weight stool) at 8 weeks and 16 weeks. | 8 weeks,16 weeks | 
| Fecal Lactobacillus counts | Total fecal Lactobacillus counts (mean log10 counts / g wet-weight stool) at 8 weeks and 16 weeks. | 8 weeks,16 weeks | 
| Stool short-chain fatty acid | Total stool short-chain fatty acid metabolites in mg/g dry stool at 8 weeks and 16 weeks. | 8 weeks,16 weeks |