The objective of this study was to investigate the bioequivalence of Mylan's levothyroxine
sodium 200 μg tablets to Abbott's Synthroid® 200 μg tablets following a single 600 μg (3 x
200 μg) dose administration in healthy volunteers under fasting conditions. Twenty-nine
healthy, non-smoking, subjects between the ages of 18 and 47 completed this open-label,
randomized, two-period, two-treatment, single-dose crossover study conducted by Dr. James D.
Carlson at PRACS Institute, Ltd., Fargo, ND. Statistical analysis of the data revealed that
90% confidence intervals were within the acceptable bioequivalent range of 80% and 125% for
the natural log transformed parameters LNAUC0-48hr and LNCPEAK for baseline corrected total
L-thyroxine. This study demonstrated that Mylan's 200 μg levothyroxine sodium tablets are
bioequivalent to Abbott's Synthroid® 200 μg tablets following a single, oral 600 μg (3 x 200
μg) dose under fasting conditions
1. Age: 18-50 years.
2. Sex: Men and/or non-pregnant, non-lactating women.
1. Women of childbearing potential must have negative serum β human chorionic
gonadotropin (HCG) pregnancy tests performed within 14 days prior to of the
study and on the evening prior to each dose administration. An additional serum
(β HCG) pregnancy test will be performed upon completion of the study.
2. Women of childbearing potential must practice abstinence or be using an
acceptable form of contraception throughout the duration of the study. Oral
contraceptives are not to be used within 3 months prior to dosing and throughout
the course of the study due to the fact that they increase serum TBG
concentrations, and therefore, elevate T4. Acceptable forms of contraception
include the following:
1. intrauterine device in place for at least 3 months prior to the start of
the study and remaining in place during the study period, or
2. barrier methods containing or used in conjunction with a spermicidal agent,
3. postmenopausal accompanied with a documented postmenopausal course of at
least one year or surgical sterility (tubal ligation, oophorectomy or
3. Weight: At least 60 kg (132 lbs) for men and 48 kg (106 lbs) for women, and within
15% of Ideal Body Weight (IBW), as referenced by the Table of "Desirable Weights of
Adults" Metropolitan Life Insurance Company, 1983 (See Part II Administrative Aspects
of Bioequivalence Protocols).
4. All subjects should be judged normal (euthyroid) and healthy during a prestudy
medical evaluation (physical examination, laboratory evaluation, blood chemistry,
serum T4 (free and total), serum T3 (total only), serum thyroid-stimulating hormone
(TSH), serum thyroxine-binding globulin (TBG), hepatitis B and hepatitis C tests,
HIV test, 12-lead ECG, and urine drug screen including amphetamine, barbiturates,
benzodiazepine, cannabinoid, cocaine, opiate screen, phencyclidine, and methadone)
performed within 14 days of the initial dose of study medication.
1. Institutionalized subjects will not be used.
2. Social Habits:
1. Use of any tobacco products within 1 year of the initial study drug
2. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage
within the 48 hours prior to the initial dose of study medication.
3. Ingestion of any vitamins within the 48 hours prior to the initial dose of the
4. Any change in dietary or exercise habits throughout the duration of the study.
1. Use of any medication within the last 30 days prior to the initial dose of study
medication, during the study or during the washout period. These may include
but is not limited to: infant soybean formula, steroids, salicylates, androgenic
or estrogenic hormones including oral contraceptives; preparations containing
iodine, such as vitamins; oral anti-diabetic agents; all resins for lowering of
cholesterol, such as cholestyramine; sucralfate, propranolol, amiodarone,
phenytoin, carbamazepine, furosemide; aluminum-containing antacids, including
aluminum hydroxide; rifampin, calcium channel blockers and ferrous sulfate.
2. Use of any medication known to alter hepatic enzyme activity within 28 days
prior to the initial dose of study medication.
1. History of any significant chronic disease and/or hepatitis.
2. History of drug and/or alcohol abuse.
3. Acute illness at the time of either the prestudy medical evaluation or dosing.
4. History of any thyroid disease.
5. Subjects with any underlying medical condition known to interfere with the
absorption or metabolism of thyroid hormones.
5. Abnormal and clinically significant laboratory test results:
1. Clinically significant deviation from the Guide for Clinically Relevant
Abnormalities (See Part II Administrative Aspects of Bioavailability Protocols).
2. Abnormal and clinically relevant ECG tracing.
3. Abnormal thyroid function tests.
6. Donation or loss of a significant volume of blood or plasma (> 450 ml) within 28 days
prior to the initial dose of study medication.
7. Subjects who received any surgical treatment within 6 months prior to the initial
dose of study medication.
8. Subjects with known allergies or hypersensitivity to thyroid preparations.
9. Subjects who have received an investigational drug within 30 days prior to the
initial dose of study medication.