A Study of Armour® Thyroid Compared to Synthetic T4 (Levothyroxine) in Previously Hypothyroid Participants

Study Overview
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Brief Summary
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This study will evaluate the safe and effective dose conversion from levothyroxine (synthetic T4) therapy to Armour Thyroid therapy in participants who are on a stable dose of levothyroxine and have thyroid stimulating hormone (TSH) levels within the normal reference range.

Detailed Description
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This study will include will include a Screening Period, double-blinded Titration Period (at least 18 weeks, up to 36 weeks), and a double-blinded Stabilization Period (12 weeks). Participants will be randomized to receive either their same dose of levothyroxine or an approximately, matching dose of Armour Thyroid, using a dose-conversion chart based on the United States Pharmacopeia (USP) Drug Information 2000, which states that 1 grain of Armour Thyroid is equivalent to 100 mcg of levothyroxine. During the Titration Period, Investigators will have the option to up-or down-titrate a participant's dose as needed based on the participant's TSH level (normal reference range 0.45 - 4.12 mIU/L, inclusive). At Week 18, if a participant's TSH levels are not within the normal reference range, the Investigator may up-or down-titrate the dose by continuing the Titration Period beyond Week 18 for up to a maximum of 3 additional titrations at 6-week intervals. Participants whose TSH levels have not normalized after the maximum 3 additional titrations will not enter the Stabilization Period. At the end of the Titration Period, participants with TSH levels within normal reference range may enter the Stabilization Period. Depending on whether a participant requires additional dose titration after the Week 18 visit, the Stabilization Period may end at Week 30, 36, 42, or 48.

Official Title
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A Multicenter, Randomized, Double-blind, Dose-conversion Study to Evaluate the Safety and Efficacy of Hormone Replacement Therapy With Armour® Thyroid Compared to Synthetic T4 (Levothyroxine) in Previously Hypothyroid Participants Who Are Euthyroid on T4 Replacement Therapy

Conditions
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Hypothyroidism, Thyroid Disease, Euthyroid, Thyroid Gland, Thyroid Hormones

Intervention / Treatment
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* Drug: Armour® Thyroid
* Drug: Levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have a diagnosis of primary hypothyroidism made ≥ 12 months before study entry (Visit 1). Be on continuous thyroid replacement therapy with synthetic T4 for primary hypothyroidism for at least 12 months immediately prior to the Screening Visit (Visit 1). Be on a stable Food and Drug Administration (FDA)-approved daily dose of synthetic T4 for a minimum of 3 months prior to the Screening Visit (Visit 1). Must enter the study on the same stable dose. Have euthyroid status indicated by at least 1 documented TSH value within normal reference range (0.45 - 4.12 mIU/L, inclusive) at a minimum of 6 weeks and maximum of 12 months prior to the Screening Visit (Visit 1). Also have a confirmed TSH value within the normal reference range drawn at the Screening Visit (Visit 1). Male and female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period (35 days after last dose of study intervention). Exclusion Criteria: Any clinical condition or previous surgery that might affect the absorption, distribution, biotransformation, or excretion of Armour Thyroid or synthetic T4. History of alcohol or other substance abuse within the previous 5 years. Known or suspected allergy or intolerance to any ingredients of Armour Thyroid, including its excipients, levothyroxine (T4), other thyroid replacement medications, or pork products. Have received active treatment with an investigational drug within 30 days or 5 half lives, whichever is longer, of Screening Visit (Visit 1). Current enrollment in an investigational drug or device study or participation in such a study within 60 days of entry into this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Armour® Thyroid<br>Participants were randomized to receive Armour Thyroid at a dose corresponding to their pre-randomized dose of synthetic T4. During the first 18 to 36 weeks (titration period) the dose of Armour Thyroid could be titrated based on levels of thyroid stimulating hormone (TSH), in order to achieve TSH levels within the normal reference range (0.45 - 4.12 mIU/L, inclusive). Once TSH levels were within the normal reference range, participants continued to receive a stable dose of Armour Thyroid for an additional 12 weeks (stabilization period). | Drug: Armour® Thyroid<br>* Administered orally once a day. the daily dose could range from 1/4 - 2 grains.<br>* Other names: AGN-204771;|
| Active Comparator: Levothyroxine<br>Participants were randomized to receive levothyroxine at their pre-randomized dose. During the first 18 to 36 weeks (titration period) the dose of levothyroxine could be titrated based on levels of TSH in order to achieve TSH levels within the normal reference range (0.45-4.12 mIU/L, inclusive). Once TSH levels were within the normal reference range, participants continued to receive a stable dose of levothyroxine for an additional 12 weeks (stabilization period). | Drug: Levothyroxine<br>* Administered orally once a day; the daily dose could range from 25- 200 µg.<br>* Other names: Synthetic T4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of participants who are Sustained Thyroid-Stimulating Hormone (TSH) Responders | Participants whose TSH values are within the normal reference range among participants who received at least 1 dose of study intervention | Up to week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent of participants who are Titration TSH Responders | Participants whose TSH values are within the normal reference range among participants who received at least 1 dose of study intervention | Up to week 48 |