Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)

A Randomized Comparative Study Between Liquid (Tirosint®-SOL) and Tablet Formulations of Levothyroxine in Neonates and Infants With Congenital Hypothyroidism

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).

Study Overview

• Status: Terminated
• Conditions: Congenital Hypothyroidism
• Intervention / Treatment: Drug: Tirosint®-SOL; Drug: Levothyroxine Sodium

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Orange, California, United States, 92868
      • CHOC Children's Hospital
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Hospital of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Children's Mercy Hospital and Clinics
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Children's Hospital Medical Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Health Care Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 9 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patient aged 0 to 9 months

• Primary CH diagnosis with elevated TSH and low or normal FT4, 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 3 weeks;
• Provide and comply with the informed consent.

Exclusion Criteria:

• Preterm neonates with a gestational age < 37 weeks;
• Low birth weight (LBW) or very low birth weight (VLBW) neonates (weight < 2.5 kg) or VLBW infants (weight < 1.5 kg);
• Neonates in neonatal intensive care units or requiring admission to NICU or neonates/infants hospitalized or requiring hospitalization or in fragile health conditions (e.g. with serious health problems or complications);
• Neonates with CH diagnosis > 4 weeks after delivery;

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: levothyroxine sodium tablets
Experimental: Treatment; Tirosint®-SOL (levothyroxine sodium) oral solution (IBSA Pharma Inc.) at the following strengths: 13, 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: levothyroxine sodium oral solution (liquid)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LT4 Dose Required to Maintain TSH in Target Range (Unit: mcg/kg/Day)	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	1 year of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hormonal Profile for TSH	TSH (unit mIU/L)	1 year of age
Hormonal Profile for FT4	FT4 (unit pmol/L)	1 year of age
Frequency of Dose Adjustments	Percent number of subjects (%) who need a dose adjustment in the long-term follow up phase	Up to 22 months based on age group
Number of Events of TSH Values Above 4.5 mU/L	TSH values above 4.5 mU/L	Up to 22 months based on age group
Number of Events of FT4 Values Below the Middle of the Laboratory Normal Range	FT4 values below the middle of the laboratory normal range	Up to 22 months based on age group
Growth Pattern for Length of Body	Subject growth measurements in Length (cm) of body	1 year of age
Growth Pattern for Body Weight	Subject growth measurements in Body weight (kg)	1 year of age
Growth Pattern for Head Circumference	Subject growth measurements in Head circumference (cm)	1 year of age
Parent/Caregiver Reports of Satisfaction and Ease of Administration	Parents Satisfaction Questionnaire is a study-specific tool measuring coping and mental well-being and satisfaction in 20 questions. 12 of these questions were scored from 1 to 5, with higher score meaning better outcome. Subject scores were calculated for each subject by visit as mean of the LN(single question score) [min=0; max=1.61].	3 weeks after treatment start
Subject Acceptance of the Treatment (CareCAT)	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	first treatment week
Signs and Symptoms of Hypothyroidism	Total number of subjects experiencing hypothyroidism's signs and symptoms	Up to 22 months based on age group
Signs and Symptoms of Hyperthyroidism	Total number of subjects experiencing hyperthyroidism's signs and symptoms	Up to 22 months based on age group

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Normalize TSH in Neonates	Time to normalize TSH into reference range (unit: days), computed as: (date of first TSH result into reference ranges - date of first LT4 dose intake + 1)	Up to 28 days
Time to Normalize FT4 in Neonates	Time to normalize FT4 into the upper half of the laboratory normal FT4 range (unit: days), computed as: (date of first FT4 result into the upper half of the laboratory reference ranges - date of first LT4 dose intake + 1)	Up to 6 months

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA
• Collaborators: Cromsource
• Investigators: Study Director: Giuseppe Mautone, IBSA Head of R&D Scientific Affairs

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Actual): March 27, 2025
• Study Completion (Actual): March 27, 2025

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Bone Diseases, Endocrine; Bone Diseases, Developmental; Dwarfism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypothyroidism; Congenital Hypothyroidism; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Peptides, and Proteins; Therapeutics; Drug Therapy; Amino Acids; Amino Acids, Aromatic; Amino Acids, Cyclic; Thyroid Hormones; Fluid Therapy; Thyroxine
• Other Study ID Numbers: 20US-T414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No