Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)
Study Details
Study Description
Brief Summary
This is a multi-center, prospective, parallel-group, open-label, randomized clinical study in one hundred and twenty-six (126) neonates and infants diagnosed with CH.
Subjects will be randomized in a 2:1 ratio to Treatment (Tirosint®-SOL) or Control (conventional therapy with levothyroxine sodium crushed tablets).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Newly diagnosed neonates will be randomly assigned to start therapy with LT4 at the initial dose recommended by the Standard of Care (SOC). Infants already on LT4 therapy will continue at the same daily dose within the randomly assigned treatment group (dose adjustments are allowed, if needed based on laboratory parameters and clinical response). Once enrolled, subjects will be treated and followed for 12 months (±1.5 months), participating in 7-8 study visits, consisting of 6-7 inclinic and 1-2 (or more if follow-up visits are required) telemedicine (TM) visits. The total number of visits depends on the age at inclusion.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Tirosint®-SOL (levothyroxine sodium) oral solution (IBSA Pharma Inc.) at the following strengths: 25, 37.5, 44, 50, 62.5, 75, 88, 100 mcg. |
Drug: Tirosint®-SOL
Dosage will be according to the USPI and Standard of Care.
Other Names:
|
| Active Comparator: Control Crushed levothyroxine sodium tablets |
Drug: Levothyroxine Sodium
Tablets will be crushed and dissolved in solution. Dosage will be according to the USPI and Standard of Care.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- LT4 dose required to maintain TSH in target range (unit: mcg/kg/day) [Up to 22 months based on age group]
The LT4 dose is calculated based on the daily LT4 dose (mcg) used in the time period preceding the visit (or the average daily dose on a weekly basis if more than one strength is used over the course of the week) and the body weight (kg) measured during the visit.
- Hormonal (TFTs) profile for TSH [Up to 22 months based on age group]
TSH (unit mU/L)
- Hormonal (TFTs) profile for FT4 [Up to 22 months based on age group]
FT4 (unit ng/dL)
- Hormonal (TFTs) profile for TT4 [Up to 22 months based on age group]
TT4 (unit µg/dL)
- Parent/caregiver reports of satisfaction and ease of administration preferences [Up to 22 months based on age group]
Parents Satisfaction Questionnaire is a study-specific tool measuring coping and mental well-being and satisfactions. Score: 1-Strongly disagree, 2-Disagree, 3-Neutral, 4-Agree, 5-Strongly agree. The minimum score of 1 is worse outcome and maximum score of 5 is best outcome.
- Subject acceptance of the treatment (CareCAT) [Up to 22 months based on age group]
Caregiver Administered Children's Acceptance Tool (CareCAT) is a 5-point nominal scale used to assess the acceptance of oral medicines in infants and toddlers who are unable to verbally give their opinion about a medicine (Blume 2018). Scale: 1-Swallows well, 2-Refusal, 3-Spitting Up, 4-Vomiting, 5-Medication not taken. The minimum score of 1 is best outcome and maximum score of 5 is worse outcome.
Secondary Outcome Measures
- Frequency of dose adjustments [Up to 22 months based on age group]
Percent number of subjects (%) who need a dose adjustment in the long-term follow up phase
- Growth patterns for length of body [Up to 22 months based on age group]
Subject growth measurements in Length (cm) of body
- Growth patterns for body weight [Up to 22 months based on age group]
Subject growth measurements in Body weight (kg)
- Growth patterns for head circumference [Up to 22 months based on age group]
Subject growth measurements in Head circumference (cm)
Other Outcome Measures
- Time to normalize TSH in neonates [Up to 28 days]
Time to normalize TSH into reference range (unit: days)
- Time to normalize FT4 in neonates [Up to 28 days]
Time to normalize FT4 into the upper half of the laboratory normal FT4 range (unit: days)
- Signs and symptoms of hypothyroidism [Up to 22 months and through 30 days post-discontinuation or until AE resolution or stabilization]
Total number of subject experiencing hypothyroidism's signs and symptoms (N=126)
- Signs and symptoms of hyperthyroidism [Up to 22 months and through 30 days post-discontinuation or until AE resolution or stabilization]
Total number of subject experiencing hyperthyroidism's signs and symptoms (N=126)
- Adverse events [Up to 22 months and through 30 days post-discontinuation or until AE resolution or stabilization]
Assessing the total number of adverse event incidence between the study drug and the control treatment (N=126)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and female patient aged 0 to 9 months
-
Primary CH diagnosis with elevated TSH and low T4, requiring treatment with LT4, under either of the following conditions:
-
Neonates newly diagnosed with primary CH and needing to initiate LT4 therapy, or
-
Infants previously diagnosed with primary CH and who are already on LT4 therapy for at least 4 weeks;
-
Provide and comply with the informed consent.
Exclusion Criteria:
-
Preterm neonates with a gestational age < 37 weeks;
-
Low birth weight and very low birth weight neonates (weight < 2.5 kg);
-
Neonates in neonatal intensive care units or requiring admission to NICU or neonates/infants hospitalized or requiring hospitalization;
-
CH diagnosis > 4 weeks after delivery (for newly diagnosed neonates only);
-
Diagnosis of primary gastrointestinal disease:
-
Gastroesophageal reflux requiring medical therapy (beyond thickening of formula or position);
-
Anatomic defects (e.g. intestinal atresia, malrotation, tracheoesophageal fistula, pyloric stenosis, Hirschsprung's disease, gastroschisis);
-
Dietary allergy (e.g. cow's milk protein allergy);
-
Malabsorption related to cystic fibrosis, celiac disease and others;
-
Necrotizing enterocolitis requiring surgical resection;
-
Known or suspected adrenal insufficiency (e.g. congenital adrenal hyperplasia, hypopituitarism);
-
Diagnosis of congenital cardiac disease, cardiac insufficiency or risk for cardiac failure;
-
Diagnosis of chromosomopathy;
-
Diagnosis of central hypothyroidism;
-
Hypersensitivity to glycerol;
-
Concomitant anticonvulsant medications, liothyronine, combination of LT4 and liothyronine, thyroid extracts and/or chronic or long-term use of systemic glucocorticoids
-
History of nonadherence with medication or medical visit schedule; or
-
Any condition for which, participation would not be in the best interest of the patient or that could limit protocol specified assessments.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Los Angeles | Los Angeles | California | United States | 90027 |
| 2 | CHOC Children's Hospital | Orange | California | United States | 92868 |
| 3 | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | United States | 60611 |
| 4 | Children's Mercy Hospital and Clinics | Kansas City | Missouri | United States | 64111 |
| 5 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 6 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | Cook Children's Health Care Systems | Fort Worth | Texas | United States | 76104 |
Sponsors and Collaborators
- IBSA Institut Biochimique SA
- Cromsource
Investigators
- Study Director: Giuseppe Mautone, IBSA Head of R&D Scientific Affairs
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20US-T414