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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypothyroidism
• Intervention / Treatment: Drug: levothyroxine sodium

Detailed Description

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
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento, Inc.
    • Montclair, California, United States, 91763
      • Catalina Research Institute, L.L.C.
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research, LLC
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation
    • Sugar Land, Texas, United States, 77479
      • Mt. Olympus Medical Research, LLC
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XP-8121; XP-8121 100 to 1500 μg subcutaneous injection	Drug: levothyroxine sodium; Levothyroxine sodium 10 mg/mL; Other Names: XP-8121

What is the study measuring?

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. 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.	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.	Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period
Tolerability Assessment: Modified Draize Scale - Edema	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.	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.	Week 1 dosing in the Titration Period through Day 22 dosing in the Maintenance Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Normalized TSH Throughout the Maintenance Period	Proportion of participants enrolled with normalized TSH throughout the Maintenance Period	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.	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	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	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	Up to Day 29 of the Maintenance Period

Collaborators and Investigators

• Sponsor: Xeris Pharmaceuticals
• Investigators: Study Director: Valentina Conoscenti, MD, Xeris Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: April 9, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism
• Other Study ID Numbers: XP-8121-120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No