Hypothyroidism;Postablative
Conditions
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.
Interventions
DRUGlevothyroxine sodium capsule
after the run-in period, patients will be switched to levothyroxine sodium capsule at the same dose used during run-in
for the whole study duration all subjects will keep taking their proton pump inhibitor medication, as per prescription and as before inclusion
during the run-in period, subjects will continue taking their levothyroxine sodium tablet medication as per prescription and as before inclusion
Sponsors
IBSA Institut Biochimique SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thyroid Stimulating Hormone (TSH) | baseline and 12 weeks | Change in Serum Levels of TSH (Thyroid Stimulating Hormone) from Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Free Thyroxine (FT4) | baseline and 12 weeks | Change in Serum Levels of FT4 (free thyroxine) from Baseline |
| Total Thyroxine (TT4) | baseline and 12 weeks | Change in Serum Levels of TT4 (total thyroxine) from Baseline |
| Free Triiodothyronine (FT3) | baseline and 12 weeks | Change in Serum Levels of FT3 (free triiodothyronine) from Baseline |
| Total Triiodothyronine (TT3) | baseline and 12 weeks | Change in Serum Levels of TT3 (total triiodothyronine) from Baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Creatine Phosphokinase (CPK) | baseline and 12 weeks | Change in Serum Levels of creatine phosphokinase (CPK) from Baseline |
| Sex Hormone Binding Globulin (SHBG) | baseline and 12 weeks | Change in Serum Levels of SHBG (sex hormone binding globuline) from Baseline |
| Ferritin | baseline and 12 weeks | Change in Serum Levels of ferritin from Baseline |
| Very Low Density Lipoprotein (VLDL)-Cholesterol | baseline and 12 weeks | Change in Very Low Density Lipoprotein (VLDL)-cholesterol levels from baseline |
| High Density Lipoprotein (HDL)-Cholesterol | baseline and 12 weeks | Change in High Density Lipoprotein (HDL)-cholesterol levels from baseline |
| Angiotensin Converting Enzyme (ACE) | baseline and 12 weeks | Change in Serum Levels of ACE (angiotensin converting enzyme) from Baseline |
| Triglycerides | baseline and 12 weeks | Change in triglycerides levels from Baseline |
| Cholesterol, Total | baseline and 12 weeks | Change in total cholesterol levels from Baseline |
| Low Density Lipoprotein (LDL)-Cholesterol | baseline and 12 weeks | Change in low density lipoprotein (LDL)-cholesterol levels from baseline |
Countries
United States
Participant flow
Recruitment details
Subject were recuited by endocrinologists, either at hospital sites or at private practices
Pre-assignment details
Enrolled subjects underwent a run-in period of 28-42 days, that may be extended up to 4 months, until Thyroid Stimulating Hormone (TSH) normalization, if levothyroxine sodium (LT4) dose adjustments were necessary at screening visit.
Participants by arm
| Arm | Count |
|---|---|
| Tirosint Capsules During the run-in period, subjects continued taking their levothyroxine sodium tablet medication 88 to 250 mcg/day (depending on individual needs) as per prescription and as before inclusion.
After the run-in period, at baseline visit, subjects were switched to Tirosint (levothyroxine sodium) capsules at the same dose used during run-in and for 3 months (treatment period).
For the whole study duration (run-in and treatment period), subjects kept taking their proton pump inhibitor medication, as per prescription and as before inclusion. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Run-in | Screening failure | 8 |
| Run-in | Sponsor Decision To Discontinue Due To Global Covid-19 Pandemic | 8 |
| Run-in | Withdrawal by Subject | 3 |
| Treatment Period | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Tirosint Capsules |
|---|---|
| Age, Continuous | 55.38 years STANDARD_DEVIATION 11.111 |
| Body Mass Index (BMI) | 32.25 kg/m^2 STANDARD_DEVIATION 8.286 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants |
| Race/Ethnicity, Customized Ecuadorian | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants |
| Race/Ethnicity, Customized Peru | 1 Participants |
| Race/Ethnicity, Customized Puerto Rican | 1 Participants |
| Race/Ethnicity, Customized White | 32 Participants |
| Region of Enrollment United States | 47 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 11 Participants |
| Thyroid Stimulating Hormone (TSH) | 1.341 mIU/L STANDARD_DEVIATION 1.5054 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 47 |
| other Total, other adverse events | 13 / 47 | 10 / 47 |
| serious Total, serious adverse events | 1 / 47 | 2 / 47 |
Outcome results
Primary
Thyroid Stimulating Hormone (TSH)
Change in Serum Levels of TSH (Thyroid Stimulating Hormone) from Baseline
Time frame: baseline and 12 weeks
Population: intention to treat (ITT), 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Thyroid Stimulating Hormone (TSH) | -0.676 mIU/L | Standard Deviation 1.3181 |
p-value: <0.0001Mixed Models Analysis
Secondary
Free Thyroxine (FT4)
Change in Serum Levels of FT4 (free thyroxine) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Free Thyroxine (FT4) | 0.593 pmol/L | Standard Deviation 2.7439 |
p-value: 0.1607Mixed Models Analysis
Secondary
Free Triiodothyronine (FT3)
Change in Serum Levels of FT3 (free triiodothyronine) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Free Triiodothyronine (FT3) | 0.263 pmol/L | Standard Deviation 0.5716 |
p-value: 0.0062Mixed Models Analysis
Secondary
Total Thyroxine (TT4)
Change in Serum Levels of TT4 (total thyroxine) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Total Thyroxine (TT4) | 2.558 nmol/L | Standard Deviation 27.2426 |
p-value: 0.4204Mixed Models Analysis
Secondary
Total Triiodothyronine (TT3)
Change in Serum Levels of TT3 (total triiodothyronine) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Total Triiodothyronine (TT3) | 0.098 nmol/L | Standard Deviation 0.3158 |
p-value: 0.0438Mixed Models Analysis
Other Pre-specified
Angiotensin Converting Enzyme (ACE)
Change in Serum Levels of ACE (angiotensin converting enzyme) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 9 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Angiotensin Converting Enzyme (ACE) | -0.395 U/L | Standard Deviation 11.6237 |
p-value: 0.5542Mixed Models Analysis
Other Pre-specified
Cholesterol, Total
Change in total cholesterol levels from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 7 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Cholesterol, Total | -0.198 mmol/L | Standard Deviation 0.6685 |
p-value: 0.0468Mixed Models Analysis
Other Pre-specified
Creatine Phosphokinase (CPK)
Change in Serum Levels of creatine phosphokinase (CPK) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 6 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Creatine Phosphokinase (CPK) | -35.073 U/L | Standard Deviation 125.1454 |
p-value: 0.0254Mixed Models Analysis
Other Pre-specified
Ferritin
Change in Serum Levels of ferritin from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Ferritin | -6.442 mcg/L | Standard Deviation 30.239 |
p-value: 0.0655Mixed Models Analysis
Other Pre-specified
High Density Lipoprotein (HDL)-Cholesterol
Change in High Density Lipoprotein (HDL)-cholesterol levels from baseline
Time frame: baseline and 12 weeks
Population: ITT, 7 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | High Density Lipoprotein (HDL)-Cholesterol | -0.029 mmol/L | Standard Deviation 0.246 |
p-value: 0.4291Mixed Models Analysis
Other Pre-specified
Low Density Lipoprotein (LDL)-Cholesterol
Change in low density lipoprotein (LDL)-cholesterol levels from baseline
Time frame: baseline and 12 weeks
Population: ITT, 8 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Low Density Lipoprotein (LDL)-Cholesterol | -0.210 mmol/L | Standard Deviation 0.5609 |
p-value: 0.0203Mixed Models Analysis
Other Pre-specified
Sex Hormone Binding Globulin (SHBG)
Change in Serum Levels of SHBG (sex hormone binding globuline) from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 4 subjects not considered in the analysis because of drop-out or LT4 dose change
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Sex Hormone Binding Globulin (SHBG) | 0.884 nmol/L | Standard Deviation 19.1861 |
p-value: 0.7619Mixed Models Analysis
Other Pre-specified
Triglycerides
Change in triglycerides levels from Baseline
Time frame: baseline and 12 weeks
Population: ITT, 7 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Triglycerides | 0.075 mmol/L | Standard Deviation 0.5419 |
p-value: 0.682Mixed Models Analysis
Other Pre-specified
Very Low Density Lipoprotein (VLDL)-Cholesterol
Change in Very Low Density Lipoprotein (VLDL)-cholesterol levels from baseline
Time frame: baseline and 12 weeks
Population: ITT, 8 subjects not considered in the analysis because of drop-out, LT4 dose change or laboratory test not performed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tirosint Capsules | Very Low Density Lipoprotein (VLDL)-Cholesterol | 0.049 mmol/L | Standard Deviation 0.2338 |
p-value: 0.5967Mixed Models Analysis