Forty-six (46) eligible, healthy subjects who provide written informed consent will be
enrolled to participate in a 2 arm parallel group study to assess and compare the
pharmacokinetics and safety profile of Thyrogen dosed at 0.1 mg versus a modified release
formulation of recombinant human thyroid stimulating hormone (rhTSH) dosed at 0.1 mg. Ten
(10) of these subjects will have the thyroid uptake of radioiodine (123I) measured at
baseline and following their single dose of study medication. All doses will be administered
via intramuscular (IM) injection.
Following confirmation of study eligibility, subjects will be randomized in a 1:1 ratio to
receive either a single administration of 0.1 mg of Thyrogen (THYR) or 0.1 mg of the
Randomization will be stratified by whether or not patients will have the thyroid uptake of
radioiodine (123I) measured following their single dose of study medication. Five (5)
patients in each treatment arm will have uptake measured, while 18 in each arm will not.
Each subject will have blood samples taken to determine the pharmacokinetics of serum TSH at
-12 hours and just prior to dosing and at various hours up to 14 days following the
administration of Thyrogen or the modified release formulation. In addition, for the
evaluation of pharmacodynamics, each subject will have samples of blood taken to determine
serum free T4, total T4, free T3, and total T3 at -12 hours and just prior to dosing and at
various hours up to 14 days following the administration of study treatments.
All subjects will undergo a 12-lead electrocardiogram (ECG) just prior to dose
administration and 1, 2, 3, 4, 5, 7, 10 and 14 days following study treatment
administration. In addition, subjects will undergo 24 hours of Holter monitoring at
baseline and four (4) consecutive 24-hour Holter monitoring sessions post treatment to yield
a total of 96 hours of continuous monitoring of cardiac function following treatment
administration. All subjects will undergo ultrasound evaluations to determine thyroid
volume at baseline and 48 hours following treatment administration.
Twenty-four hours following the administration of Thyrogen or the modified release
formulation, a subset of five (5) subjects in each treatment arm will receive a dose of 123I
prepared to be 400µCi on the day of radioiodine administration based on the utilized nuclear
pharmacy's calibration schedule. Thyroid gland uptake will be measured via a probe in these
10 subjects at 6, 24 and 48 hours following radioiodine administration.
Blood chemistry, complete blood count (CBC), urinalysis and a physical exam will be
conducted 14 days after treatment administration, or at the time of early termination, as a
final safety assessment.
Each subject's duration of study participation will be approximately 4 weeks.
- Committed to follow the protocol requirements as evidenced by providing written
informed consent prior to any study-related procedures being performed
- Males or females, in good general health, between the ages of 18 and 40, inclusive.
Females of childbearing potential must be on a stable hormonal contraceptive regimen
(defined as > 6 months continuous use) and/or utilize a double barrier method, i.e.,
condom and foam. It is recommended that female sexual partners of male subjects
utilize the above described method of birth control while their partners are
participating in the study.
- A negative serum pregnancy test prior to entering the study (all women regardless of
child bearing potential)
- Physical examination, including vital signs and laboratory assessments that are
within normal limits at the time of screening. If abnormalities are noted, they must
be deemed clinically insignificant, based on the investigator's judgment, to satisfy
- Electrocardiogram (ECG) and Holter results within normal limits at screening.
Subjects who have ECG findings of occasional premature atrial beats, abnormal PR
intervals not associated with supraventricular tachycardia (SVT) or heart block,
right bundle branch block, sinus tachycardia at rest (heart rate [HR] < 100 beats per
minute [BPM]) and sinus bradycardia (HR > 50 BPM) may be included in this study.
- Urine and plasma drug screens are negative for drugs of abuse at the time of
- Willing and able to abstain from alcohol 48 hours prior to and post each
administration of Thyrogen and otherwise limit all alcohol consumption to < 2 drinks
per day while participating in the study
- Absence of or current smoking habit of < 10 cigarettes per day while participating in
- Baseline levels of total T3, free T3, free T4, T4, and TSH levels within the normal
- Body mass index (BMI) < 30
- Any history of cardiovascular disease
- Uncontrolled hypertension as defined by a resting blood pressure of > 140/90 mm Hg
(resting defined as 5 minutes sitting/supine position)
- Currently or within the past 5 years a history of malignancy, other than squamous or
basal cell carcinoma of the skin or carcinoma in situ of the cervix
- A concurrent major medical disorder (e.g., documented cardiac disease, debilitating
cardiopulmonary disease, advanced renal failure, advanced liver disease, advanced
pulmonary disease, or advanced cerebral vascular disorder) and may be too ill to
adequately comply with the requirements of this study
- ECG or Holter abnormalities that may be suggestive of underlying cardiac disease
including: left atrial abnormality and/or left ventricular hypertrophy, frequent
ectopic or multifocal atrial beats, frequent premature ventricular beats, significant
conduction abnormalities such as widened QRS, left bundle branch block, significant
axis deviation, atrial fibrillation or flutter, frequent premature ventricular
contractions or ventricular tachycardia (including torsades de point), repolarization
changes suggestive of myocardial ischemia (e.g., ST-T wave abnormalities suggestive
of ischemia), evidence of a previous myocardial infarction, atrioventricular (AV)
nodal reentrant tachycardia or tachycardias associated with preexcitation/accessory
pathway syndromes and high grade AV block
- A non-thyroidal condition known to affect 123I uptake (e.g., congestive heart failure
class III or IV, renal failure)
- Currently taking drugs that may affect thyroid or renal function (e.g.,
corticosteroids, diuretics, lithium, amiodarone, or other prescribed
- Women of childbearing potential unless taking medically acceptable contraceptive
- Women who are pregnant or lactating
- A current diagnosis or recent history, within the past 2 years, of alcoholism, drug
abuse, or severe emotional, behavioral or psychiatric problems that, in the opinion
of the Investigator, would hinder adequate compliance with the requirements of this
- Currently participating in another investigational drug study or have participated in
such a study within 30 days of their enrollment in this study
- Have schedule or travel plans that prevent the completion of all required visits