Levothyroxine Sodium in Thyroidectomized Patients Taking Proton Pump Inhibitors

NCT03094416 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 13US-T404
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 9

Brief Summary

This is an open-label therapeutic efficacy study of Tirosint (levothyroxine sodium) capsules in thyroidectomized patients taking proton pump inhibitors and levothyroxine, evaluating changes in serum levels of Thyroid Stimulating Hormone (TSH) upon switch to Tirosint with respect to baseline.

Conditions

Hypothyroidism;Postablative

Outcome Measures

Primary Outcomes (1)

• Thyroid Stimulating Hormone (TSH)

  Change in Serum Levels of TSH (Thyroid Stimulating Hormone) from Baseline

  baseline and 12 weeks

Secondary Outcomes (4)

• Free Thyroxine (FT4)

  baseline and 12 weeks

• Total Thyroxine (TT4)

  baseline and 12 weeks

• Free Triiodothyronine (FT3)

  baseline and 12 weeks

• Total Triiodothyronine (TT3)

  baseline and 12 weeks

Other Outcomes (9)

• Creatine Phosphokinase (CPK)

  baseline and 12 weeks

• Sex Hormone Binding Globulin (SHBG)

  baseline and 12 weeks

• Ferritin

  baseline and 12 weeks

Study Arms (1)

levothyroxine sodium capsules

EXPERIMENTAL

levothyroxine sodium capsules 88 to 250 mcg/day (depending on individual needs) for 3 months

Drug: levothyroxine sodium capsule; Drug: Proton pump inhibitor (PPI); Drug: Levothyroxine Sodium (LT4) Tablets

Interventions

levothyroxine sodium capsule DRUG

after the run-in period, patients will be switched to levothyroxine sodium capsule at the same dose used during run-in

Also known as: Tirosint

levothyroxine sodium capsules

Proton pump inhibitor (PPI) DRUG

for the whole study duration all subjects will keep taking their proton pump inhibitor medication, as per prescription and as before inclusion

Also known as: omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole

levothyroxine sodium capsules

Levothyroxine Sodium (LT4) Tablets DRUG

during the run-in period, subjects will continue taking their levothyroxine sodium tablet medication as per prescription and as before inclusion

levothyroxine sodium capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• written informed consent duly read, signed and dated by the subject;
• aged ≥18 and ≤65 years;
• history of hypothyroidism due to total thyroidectomy;
• on stable LT4 doses for at least 6 weeks at screening (≥88 mcg daily and ≤250 mcg daily);
• TSH at screening ≥0.3 and ≤4.0 mIU/L;
• history of gastroesophageal reflux disease or associated gastrointestinal issues on prescription PPIs (i.e. omeprazole ≥20 mg daily, or esomeprazole ≥ 20 mg daily, or lansoprazole ≥ 15 mg daily, or pantoprazole ≥ 40 mg daily) for at least 8 weeks before screening visit and for whom chronic therapy with PPIs for the next 5 months has been prescribed;
• for women, adequate and continuative contraceptive measures until the end of the study, if not in menopause;
• reasonable assumption of understanding the study and willingness to take part to the study and to comply with protocol requirements.

You may not qualify if:

• suspected or ascertained non-compliance with LT4 or PPI therapy;
• subject requiring changes of levothyroxine dose;
• use of over-the-counter (OTC) PPIs;
• history of malabsorption or history of gastric bypass surgery, short-gut syndrome, inflammatory bowel disease and other conditions of the gastrointestinal tract that may affect drug absorption (e.g. celiac disease)3;
• multiple co-morbidities (e.g. cardiac heart failure, active arrhythmia or history of arrhythmia, particularly atrial fibrillation, uncompensated diabetes mellitus, uncorrected adrenal insufficiency, seriously compromised hepatic, renal and/or respiratory functions);
• neoplastic pathology, active or in remission for less than 5 years (excluding the basic thyroid pathology);
• terminal condition;
• parenteral or assisted enteral feeding;
• presence of any medical condition or other circumstances which would significantly affect the safety of the subject or decrease the chance of obtaining reliable data, achieving study objectives or completing the study;
• history of alcoholism, drug abuse or psychiatric diseases that could invalidate the informed consent or limit the subject compliance with protocol requirements;
• pregnant (positive urine pregnancy test at screening or baseline visits) or breast-feeding subject or subject planning a pregnancy in the next months;
• known hypersensitivity to the ingredients of the preparation involved in the study3;
• use of forbidden concomitant medications;
• regular consumption of soy and soy derivatives, cotton seed meals, walnuts, and dietary fibres;
• participation in other clinical studies during the 3 months prior to screening;

Sponsors & Collaborators

• IBSA Institut Biochimique SA: lead

Study Sites (9)

California Head and Neck Specialists

La Jolla, California, 92037, United States

Location

Coastal Metabolic Research Centre

Ventura, California, 93003, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010-2975, United States

Location

MedStar Union Memorial Hospital

Baltimore, Maryland, 21218, United States

Location

NYC Health + Hospitals/ Queens

New York, New York, 11432, United States

Location

Diabetes & Endocrinology Consultants, PC

Morehead City, North Carolina, 28557, United States

Location

Carolina Ear Nose and Throat Clinic

Orangeburg, South Carolina, 29118, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Stonesifer Endocrine Care & Clinical Research Inc., PS

Federal Way, Washington, 98003, United States

Location

Related Publications (1)

• Sachmechi I, Lucas KJ, Stonesifer LD, Ansley JF, Sack P, Celi FS, Scarsi C, Lanzi G, Wartofsky L, Burman KD. Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study. Thyroid. 2023 Dec;33(12):1414-1422. doi: 10.1089/thy.2023.0382. Epub 2023 Nov 16.

  PMID: 37885233 DERIVED

MeSH Terms

Interventions

Thyroxine; Proton Pump Inhibitors; Omeprazole; Esomeprazole; Lansoprazole; Dexlansoprazole; Pantoprazole; Rabeprazole; Tablets

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

Due to Covid-19 pandemic outbreak leading to discontinuation of subjects, primary endpoint was assessed on 43 subjects instead of 48 subjects (as planned in the sample size calculation). The a-posteriori study power is 91%.

Results Point of Contact

• Title: Claudia Scarsi
• Organization: IBSA

claudia.scarsi@ibsa.ch

+41583601000

Study Officials

• Kenneth D Burman, MD

  Medstar Health Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: March 29, 2017
• Study Start: July 30, 2018
• Primary Completion: June 15, 2020
• Study Completion: June 15, 2020
• Last Updated: April 5, 2022
• Results First Posted: April 5, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)