Levothyroxine Sodium in Thyroidectomized Patients Taking Proton Pump Inhibitors

Inclusion Criteria:

1. written informed consent duly read, signed and dated by the subject;

2. aged ≥18 and ≤65 years;

3. history of hypothyroidism due to total thyroidectomy;

4. on stable LT4 doses for at least 6 weeks at screening (≥88 mcg daily and ≤250 mcg
daily);

5. TSH at screening ≥0.3 and ≤4.0 mIU/L;

6. 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;

7. for women, adequate and continuative contraceptive measures until the end of the
study, if not in menopause;

8. reasonable assumption of understanding the study and willingness to take part to the
study and to comply with protocol requirements.

Exclusion Criteria:

1. suspected or ascertained non-compliance with LT4 or PPI therapy;

2. subject requiring changes of levothyroxine dose;

3. use of over-the-counter (OTC) PPIs;

4. 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;

5. 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);

6. neoplastic pathology, active or in remission for less than 5 years (excluding the
basic thyroid pathology);

7. terminal condition;

8. parenteral or assisted enteral feeding;

9. 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;

10. history of alcoholism, drug abuse or psychiatric diseases that could invalidate the
informed consent or limit the subject compliance with protocol requirements;

11. pregnant (positive urine pregnancy test at screening or baseline visits) or
breast-feeding subject or subject planning a pregnancy in the next months;

12. known hypersensitivity to the ingredients of the preparation involved in the study3;

13. use of forbidden concomitant medications;

14. regular consumption of soy and soy derivatives, cotton seed meals, walnuts, and
dietary fibres;

15. participation in other clinical studies during the 3 months prior to screening;

16. presumption of poor reliability/cooperation;

17. any reason which, in the opinion of the Investigator, would prevent the subject from
participating in the study.