Study of XP-8121 For the Treatment of Adult Subjects With Hypothyroidism

Study Overview
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Brief Summary
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This is a non-randomized, open-label, single arm, self-controlled study of XP-8121 (levothyroxine sodium) to determine a target dose conversion factor from stably dosed oral levothyroxine to XP-8121 (levothyroxine sodium) in patients with hypothyroidism and to assess the safety and tolerability of XP-8121(levothyroxine sodium) after once weekly subcutaneous injections. This study includes the following periods: Screening, Titration Period, and Maintenance Period. The study will conclude with an End of Maintenance Visit or Early Termination (ET) Visit.

Detailed Description
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This is a non-randomized, open-label, single arm, self-controlled study of XP-8121 (levothyroxine sodium) to determine a target dose conversion factor from stably dosed oral levothyroxine to XP-8121 (levothyroxine sodium) in patients with hypothyroidism and to assess the safety and tolerability of XP-8121 (levothyroxine sodium) after once weekly subcutaneous injections. This study includes the following periods: Screening, Titration Period (2 to 8 weeks), and Maintenance Period (4 weeks). A pharmacokinetic substudy will be conducted for a subset of patients during the Maintenance Period. The study will conclude with an End of Maintenance Visit or Early Termination (ET) Visit.

Official Title
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A Phase 2, Multicenter, Non-Randomized, Open-Label, Single Arm, Self-controlled Study of XP-8121 For the Treatment of Adult Subjects With Hypothyroidism

Conditions
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Hypothyroidism

Intervention / Treatment
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* Drug: levothyroxine sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent. Male or female between the ages of 18 and 65 years (inclusive) at Screening, with chronic hypothyroidism and on a stable dose of oral levothyroxine (Synthroid or an FDA-approved generic equivalent to Synthroid) or, if in the pharmacokinetic substudy, Synthroid only for at least 3 months. TSH within the normal range at Screening (central laboratory) and at least 3 months prior to Screening (documented by local laboratory). Free thyroxine within the normal range at Screening (central laboratory). Exclusion Criteria: History of hypersensitivity to levothyroxine (any formulation). Current dose of oral levothyroxine, based on body weight >2 μg/kg/day. Current levothyroxine total daily dose either <50 μg or >375 μg. Current use of combined thyroid treatment (i.e., Synthroid plus liothyronine or Synthroid plus Armour Thyroid) and/or any other levothyroxine aside from those used in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XP-8121<br>XP-8121 100 to 1500 μg subcutaneous injection | Drug: levothyroxine sodium<br>* Levothyroxine sodium 10 mg/mL<br>* Other names: XP-8121;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose conversion factor | Geometric mean ratio of the weekly dose of XP-8121 to the daily dose of oral levothyroxine (aka dose conversion factor), where the XP-8121 dose corresponds to the administration immediately preceding collection of blood TSH used to determine normalization at the end of Maintenance Period | Day 29 of the Maintenance Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects enrolled with normalized TSH | Proportion of subjects enrolled with normalized TSH at the end of Maintenance Period | Day 29 of the Maintenance Period | 
| Thyroid hormone concentrations | Blood thyroid hormone concentrations (total thyroxine, free thyroxine and TSH) following the first dose of XP-8121 in the Titration Period | Day 8 |