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

Xeris Pharmaceuticals46 enrolled

Overview

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.

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 participants during the Maintenance Period. The study will conclude with an End of Maintenance Visit or Early Termination (ET) Visit.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypothyroidism

Interventions

levothyroxine sodiumDRUG

Levothyroxine sodium 10 mg/mL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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. * Thyroid stimulating hormone (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.

Locations (6)

ProSciento, Inc.

Chula Vista, California, United States

Catalina Research Institute, L.L.C.

Montclair, California, United States

Panax Clinical Research, LLC

Miami Lakes, Florida, United States

American Research Corporation

San Antonio, Texas, United States

Outcomes

Primary Outcomes

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. The dose conversion factor was assessed by comparing the natural log-transformed final XP-8121 dose in μg that maintained normalized TSH throughout the Maintenance Period to the natural log-transformed daily oral levothyroxine dose the participant was taking before the study, using a linear mixed effects model with treatment as the fixed effect and subject as the random effect. Geometric least square means (LSMs) were calculated by exponentiating the LSM from the ANOVA. The geometric mean ratio and the corresponding 90% CI was found by exponentiating the differences of log-transformed LSM and 90% confidence interval (CI) of the difference.

Time frame: Day 29 of the Maintenance Period

Tolerability Assessment: Modified Draize Scale - Erythema

The Modified Draize Scale assessment of erythema and edema was conducted 30 (+/-5) minutes after each dosing. The Modified Draize Scale is a 5-point scale: 0-none, 1-very slight, 2-slight, 3-moderate, 4-severe.

Time frame: Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period

Tolerability Assessment: Modified Draize Scale - Edema

Time frame: Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period

Tolerability Assessments: Injection Site Discomfort Evaluation

Injection site discomfort was assessed by each participant at 10 (+/-2) minutes post-injection.

Time frame: Week 1 dosing in the Titration Period through Day 22 dosing in the Maintenance Period

Secondary Outcomes

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Proportion of Participants With Normalized TSH Throughout the Maintenance Period

Proportion of participants enrolled with normalized TSH throughout the Maintenance Period

Time frame: Day 29 of the Maintenance Period

Proportion of Participants With Normalized TSH at End of Maintenance Period

Proportion of participants enrolled with normalized TSH at the end of the Maintenance Period.

Time frame: Day 29 of the Maintenance Period

Thyroid Hormone Concentrations: Total Thyroxine

Thyroid hormone concentrations (total thyroxine, free protein-unbound thyroxine (fT4), and TSH) following the first dose of XP-8121 during the Titration Period and Maintenance Periods

Time frame: Up to Day 29 of the Maintenance Period

Thyroid Hormone Concentrations: Free Thyroxine (fT4)

Thyroid hormone concentrations (total thyroxine, free protein-unbound thyroxine (fT4), and TSH) following the first dose of XP-8121 during the Titration Period and Maintenance Periods

Time frame: Up to Day 29 of the Maintenance Period

Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH)

Thyroid hormone concentrations (total thyroxine, free protein-unbound thyroxine (fT4), and TSH) following the first dose of XP-8121 during the Titration Period and Maintenance Periods

Time frame: Up to Day 29 of the Maintenance Period