Sequelae of Perinatal Brain Injury
Conditions
Brief summary
Purpose of the study: * To assess the clinical efficacy of Tenoten for children liquid dosage form therapy (10 oral drops per day for 12 weeks) in Infants with Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischaemia and/or mild-to-moderate intracranial haemorrhage). * To assess the safety of Tenoten for children liquid dosage form therapy (10 oral drops per day for 12 weeks) in Infants with Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischaemia and/or mild-to-moderate intracranial haemorrhage).
Interventions
Oral. 10 drops daily, at the same time in the morning, 15 minutes before feeding.
DRUGPlacebo
Oral. 10 drops daily, at the same time in the morning, 15 minutes before feeding.
Sponsors
Materia Medica Holding
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
29 Days to 9 Months
Healthy volunteers
No
Inclusion criteria
1. Full-term infants aged 29 days to 9 months. 2. Diagnosis of Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischemia and/or mild-to-moderate intracranial hemorrhage). 3. Total Jurba-Mastyukova score of \< 27 (but \> 12). 4. Physical development parameters within 25-27 centiles. 5. Neurologist's outpatient observation. 6. Information sheet (informed consent form) for parents/adoptive parents for participation in the clinical study signed by the child's parents/adoptive parents.
Exclusion criteria
1. Previously diagnosed lesions, diseases and conditions: 1.1. Cerebral ischemia (grade III). 1.2. Intraventricular hemorrhage (grade III). 1.3. Metabolic and toxic disorders affecting central nervous system (persistent neonatal hypoglycemia, hyperbilirubinemia associated with elevated indirect bilirubin, and other severe conditions). 1.4. Intracranial birth injury, focal impairments due to brain injuries (pareses and paralyses). 1.5. Sequelae of birth injury to spinal cord, cranial nerves and peripheral nervous system (peripheral pareses and paralyses). 1.6. Different types of hydrocephalus. 1.7. Symptomatic epilepsy and epileptic syndromes. 1.8. Sequelae of perinatal central nervous system (CNS) infectious diseases (injury to CNS caused by neonatal sepsis, encephalitis, meningitis, meningoencephalitis, ventriculitis). 1.9. Infectious diseases including congenital diseases (cytomegalovirus infection, rubella, herpesvirus or enterovirus infection, toxoplasmosis, syphilis, HIV infection, etc.). 1.10. Chronic respiratory diseases originating in the perinatal period, including bronchopulmonary dysplasia. 1.11. Hereditary metabolic diseases including glycogen storage disease (glycogenoses, E74.0), galactose metabolism disorders (galactosemia, Е74.2), other carbohydrate metabolism disorders (Е74), glucosaminoglycan metabolism disorders (mucopolysaccharidoses, Е76), aromatic amino-acid metabolism disorders (phenylketonuria, tyrosinemia, etc, Е70), branched-chain amino-acid and fatty-acid metabolism disorders (maple-syrup-urine disease, Е71), mitochondrial myopathy (G71.3). 1.12. Neurogenerative diseases including Huntington disease (G10), copper metabolism disorder (Wilson disease, Е83.0). 1.13. Chromosomal abnormalities. 1.14. Congenital anomalies \[malformations\] and deformities including congenital anomalies of nervous system and malformations of internal organs. 1.15. Congenital endocrine diseases (congenital hypothyroidism, hypoparathyroidism, adrenocortical dysfunction). 1.16. Malignant neoplasm / suspected malignant neoplasm. 2. Acute infectious disease, exacerbation / decompensation of diseases that may prevent the patients' participation in the clinical study. 3. Allergy/intolerance of any of the study treatment medications components. 4. Drug addiction, alcohol use in the volume over 2 alcohol units/day by the subject's parent(s)/adoptive parent(s). 5. Mental disorders of the patient's parent(s)/adoptive parent(s). 6. Participation in other clinical studies for a period prior to and during the course of this trial. 7. Other conditions complicating the subject's participation in the study (cannot make regular medical visits, moving, etc.). 8. Subjects whose parent(s)/adoptive parent(s), from the investigator's point of view, will not follow the study requirements or comply with the dosing regimen. 9. Patients whose parent(s)/adoptive parent(s) are related research staff of the clinical investigative site who are directly involved in the study or is a close relative of the investigator. Close relatives include spouse, parents, children or brothers (sisters) regardless of whether they are biological or adoptive ones. 10. Patients whose parent(s)/adoptive parent(s) is working in OOO NPF Materia Medica Holding, i.e. is the company official, temporary contract worker or an appointed official responsible for the study or their close relatives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment | in 12 weeks of the treatment | The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as age-appropriate normal value; 23-26 points - as an absolute risk group; 13-22 points - as developmental retardation; below 13 points - as severe global developmental delay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | in 12 weeks of the treatment | The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as age-appropriate normal value; 23-26 points - as an absolute risk group; 13-22 points - as developmental retardation; below 13 points - as severe global developmental delay. |
| Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | in 12 weeks of the treatment | The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery; the score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test; the score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills; the score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients \[DQ = (developmental age/chronologic age)\*100\]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development). |
| Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | in 12 weeks of the treatment | The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery. The score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test. The score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills. The score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients \[DQ = (developmental age/chronologic age)\*100\]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development). |
| Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | in 12 weeks of the treatment | The Clinical Global Impressions - Efficacy Index (CGI-EI) scale provide an evaluation of the treatment response. CGI-EI takes account of both therapeutic efficacy and treatment-related adverse events and ranges from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenoten for Children Tenoten for children: Oral. A dose of 10 drops daily, at the same time in the morning, 15 minutes before feeding the child.
The drops can be diluted in a small amount of room temperature drinking water (1/2 tsp.) before use. | 87 |
| Placebo Placebo: Oral. A dose of 10 drops daily, at the same time in the morning, 15 minutes before feeding the child.
The drops can be diluted in a small amount of room temperature drinking water (1/2 tsp.) before use. | 95 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Did Not Meet Exclusion Criteria | 1 | 3 |
| Overall Study | Did Not Meet Inclusion Criteria | 9 | 5 |
| Overall Study | Inability to perform procedures | 1 | 0 |
| Overall Study | Non-compliance with protocol requirement | 3 | 2 |
| Overall Study | Protocol Violation | 7 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Tenoten for Children | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 5.5 months STANDARD_DEVIATION 2 | 5.2 months STANDARD_DEVIATION 2.2 | 5.0 months STANDARD_DEVIATION 2.3 |
| Body length | 63.9 centimeter STANDARD_DEVIATION 4.6 | 63.2 centimeter STANDARD_DEVIATION 5 | 62.5 centimeter STANDARD_DEVIATION 5.3 |
| Head circumference | 42.0 centimeter STANDARD_DEVIATION 2.3 | 41.7 centimeter STANDARD_DEVIATION 2.5 | 41.4 centimeter STANDARD_DEVIATION 2.7 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 42 Participants | 83 Participants | 41 Participants |
| Sex: Female, Male Male | 45 Participants | 99 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 95 |
| other Total, other adverse events | 24 / 87 | 27 / 95 |
| serious Total, serious adverse events | 1 / 87 | 0 / 95 |
Outcome results
Primary
Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment
The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as age-appropriate normal value; 23-26 points - as an absolute risk group; 13-22 points - as developmental retardation; below 13 points - as severe global developmental delay.
Time frame: in 12 weeks of the treatment
Population: Per Protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenoten for Children | Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment | 86.1 percentage of participants |
| Placebo | Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment | 62.5 percentage of participants |
p-value: 0.002Fisher Exact
Secondary
Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course.
The Clinical Global Impressions - Efficacy Index (CGI-EI) scale provide an evaluation of the treatment response. CGI-EI takes account of both therapeutic efficacy and treatment-related adverse events and ranges from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects).
Time frame: in 12 weeks of the treatment
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tenoten for Children | Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | Therapeutic effect | 3.4 score on a scale | Standard Deviation 0.6 |
| Tenoten for Children | Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | Side effect | 1.1 score on a scale | Standard Deviation 0.3 |
| Tenoten for Children | Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | Efficacy Index | 3.2 score on a scale | Standard Deviation 0.8 |
| Placebo | Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | Therapeutic effect | 3.2 score on a scale | Standard Deviation 0.8 |
| Placebo | Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | Side effect | 1.0 score on a scale | Standard Deviation 0.1 |
| Placebo | Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course. | Efficacy Index | 3.2 score on a scale | Standard Deviation 0.8 |
p-value: 0.19Wilcoxon (Mann-Whitney)
Secondary
Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery; the score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test; the score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills; the score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients \[DQ = (developmental age/chronologic age)\*100\]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development).
Time frame: in 12 weeks of the treatment
Population: Per Protocol set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tenoten for Children | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 0 | 86.2 score on a scale | Standard Deviation 14.2 |
| Tenoten for Children | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 4 | 92.5 score on a scale | Standard Deviation 14.1 |
| Tenoten for Children | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 8 | 95.4 score on a scale | Standard Deviation 10.5 |
| Tenoten for Children | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 12 | 97.5 score on a scale | Standard Deviation 8.9 |
| Placebo | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 12 | 95.2 score on a scale | Standard Deviation 10.3 |
| Placebo | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 0 | 83.5 score on a scale | Standard Deviation 16.9 |
| Placebo | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 8 | 94.6 score on a scale | Standard Deviation 11.3 |
| Placebo | Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 4 | 90.6 score on a scale | Standard Deviation 12.9 |
p-value: 0.5Mixed Models Analysis
Secondary
Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as age-appropriate normal value; 23-26 points - as an absolute risk group; 13-22 points - as developmental retardation; below 13 points - as severe global developmental delay.
Time frame: in 12 weeks of the treatment
Population: Per Protocol set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 4 | 45.8 Percentage of patients |
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 8 | 79.2 Percentage of patients |
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 12 | 93.1 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 4 | 34.7 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 12 | 81.9 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 8 | 66.7 Percentage of patients |
p-value: 0.005Cochran-Mantel-Haenszel
Secondary
Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery. The score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test. The score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills. The score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients \[DQ = (developmental age/chronologic age)\*100\]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development).
Time frame: in 12 weeks of the treatment
Population: Per Protocol set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 0 | 81.9 Percentage of patients |
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 4 | 91.7 Percentage of patients |
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 8 | 100 Percentage of patients |
| Tenoten for Children | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 12 | 100 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 12 | 95.8 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 0 | 77.8 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 8 | 97.2 Percentage of patients |
| Placebo | Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks) | Week 4 | 91.7 Percentage of patients |
p-value: 0.2Cochran-Mantel-Haenszel