| Eligibility |
Inclusion Criteria:
- Clinical diagnosis of multinodular goiter, judged clinically and by ultrasound at
Screening to be at least 40 mL, but less than or equal to 140 mL in size.
- Clinically free of thyroid cancer as determined by Fine Needle Aspiration (FNA) of all
dominant and/or highly suspicious cold nodules in the goiter and cytology reports as
negative for thyroid cancer. (Note: Results of FNA and cytology reports that were
performed within 18 months prior to commencing Screening procedures and meet these
criteria are acceptable for inclusion).
- Principal Investigator must believe that there is a minimal risk of coexistent thyroid
cancer.
- Principal Investigator feels that the patient's iodine intake and/or levels will not
significantly impact the results of the study (urinary iodine assay at Screening and
low-iodine diet are optional and associated data will not be collected for study
purposes).
- Baseline serum level of free thyroxine index (FTI) within the normal range, as
determined by central lab.
- Baseline serum level of thyroid stimulating hormone (TSH) ranges from undetectable to
the upper limit of the normal range, as determined by central lab.
- Females of child-bearing potential must be on a stable hormonal contraceptive regimen
(i.e., > 6 months continuous use) and/or use a double barrier method (i.e., condom and
foam) through Visit 8 (i.e. the end of the Core Study).
- Through Visit 8 (6 months) of a male patient's participation in the study, it is
recommended that his sexual partner(s), who are females of child-bearing potential,
use the above described methods of contraception.
- Negative pregnancy tests for all women of child-bearing potential prior to
participating in the study. Women aged 50 years and above and considered
postmenopausal (defined as > 2 years since last menstrual period) will not need to
have a pregnancy test.
- Routine blood laboratory values within normal range at Screening, as determined by
central lab. Abnormal values considered to be not clinically significant by the
Principal Investigator are acceptable for inclusion.
- Electrocardiogram (ECG) (12 lead, 2 minute rhythm strip) within normal limits at
Screening as determined by a designated study cardiologist or appropriately qualified
physician at each site. Evidence of an old myocardial infarction (MI) will exclude the
patient. Patients who have ECG findings of occasional premature atrial beats, abnormal
PR intervals not associated with supra ventricular tachycardia (SVT) or heart block,
right bundle branch block, and heart rates = 100 beats per minute (BPM) and = 50 BPM
may be included in this study.
- Committed to follow all protocol-required study procedures as evidenced by providing
written informed consent within 21 days prior to Screening Period 2.
Exclusion Criteria:
- History of thyroid cancer.
- Previous partial or near total thyroidectomy.
- Clinical history, signs or symptoms that make thyroid cancer a higher than usual
probability, such as positive immediate family history of thyroid cancer, history of
head or neck irradiation, a stone-hard nodule or suspicious growth of a nodule in
recent months, palpable cervical lymph nodes or nodes that on ultrasound have features
suspicious for metastases (unless ruled out by biopsy or FNA).
- During the 45 days before administration of MRrhTSH or placebo (i.e., Screening
Periods 1 and 2), use of propylthiouracil, methimazole or thyroxine, vitamins or
supplements containing kelp or iodine (taking a multivitamin that does not contain
iodine or kelp is acceptable), medications that significantly affect iodine handling
such as high dose corticosteroids, high dose diuretics, or lithium (low or moderate
dose diuretic use is acceptable).
- Patient has currently or within the past 60 days used retinoic acid.
- Serum calcitonin above the upper limit of normal at Screening, as determined by
central lab.
- Use of amiodarone within the prior 2 years.
- Received iodine-containing contrast agent within the past 3 months.
- Inability to complete all required visits.
- Patients with conditions in which use of beta-blockers are medically contraindicated,
such as recently active asthma or clinically significant chronic obstructive pulmonary
disease.
- Currently or within the past 5 years have a history of malignancy, other than squamous
or basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- Prior MI, even if remote; stroke within 6 months; atrial fibrillation or clinically
significant arrhythmia within 6 months (patient may have mild hypertension or chronic
cardiac illnesses that are well controlled on a medication regimen: blood pressure
(BP) less than 140/90 mmHg after resting 5 minutes).
- A concurrent major medical disorder (e.g., documented significant cardiac disease,
debilitating cardiopulmonary disease, advanced renal failure, advanced liver disease,
advanced pulmonary disease, or advanced cerebral vascular disorder) that may have an
impact on the capability of the patient to adequately comply with the requirements of
this study.
- Women who are pregnant or lactating.
- A recent history of alcoholism, drug abuse or other disorder that might affect
compliance with the protocol.
- Received investigational study medication within 30 days prior to signing informed
consent and/or intends to participate in another clinical study involving the use of
an investigational drug over the course of study participation.
- Patients on anticoagulants except for aspirin.
- Patients known at the time of Screening due to past testing to be human
immunodeficiency virus (HIV) antibody positive or hepatitis B antigen positive (no
screening for HIV or hepatitis B should be done in the study).
- Hyperthyroid symptom scale (HSS) = 20.
- Patients who have received 131I in the past, and have had a lifetime exposure believed
to be >10 mCi (0.37GBq) of 131I.
- History of allergy to Thyrogen.
- Sodium carboxymethylcellulose (NaCMC) allergy (including prior history of anaphylaxis
following topical lidocaine, barium sulfate ingestion, or intra-articular or
parenteral corticosteroid).
- Smallest cross-sectional area of the trachea (SCAT) discovered on CT to be < 60 mm2
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