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

NCT05823012 | Completed Phase 2 Results FDA Drug

• 1 other identifier: XP-8121-120
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Hypothyroidism

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Proportion of Participants With Normalized TSH Throughout the Maintenance Period

  Day 29 of the Maintenance Period

• Proportion of Participants With Normalized TSH at End of Maintenance Period

  Day 29 of the Maintenance Period

• Thyroid Hormone Concentrations: Total Thyroxine

  Up to Day 29 of the Maintenance Period

• Thyroid Hormone Concentrations: Free Thyroxine (fT4)

  Up to Day 29 of the Maintenance Period

• Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH)

  Up to Day 29 of the Maintenance Period

Study Arms (1)

XP-8121

EXPERIMENTAL

XP-8121 100 to 1500 μg subcutaneous injection

Drug: levothyroxine sodium

Interventions

levothyroxine sodium DRUG

Levothyroxine sodium 10 mg/mL

Also known as: XP-8121

XP-8121

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xeris Pharmaceuticals: lead

Study Sites (6)

ProSciento, Inc.

Chula Vista, California, 91911, United States

Location

Catalina Research Institute, L.L.C.

Montclair, California, 91763, United States

Location

Panax Clinical Research, LLC

Miami Lakes, Florida, 33014, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Mt. Olympus Medical Research, LLC

Sugar Land, Texas, 77479, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

MeSH Terms

Conditions

Hypothyroidism

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Valentina Conoscenti, MD
• Organization: Xeris Pharmaceuticals, Inc.

Clinicaltrials@xerispharma.com

1-877-XERIS-37

Study Officials

• Valentina Conoscenti, MD

  Xeris Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 21, 2023
• Study Start: May 15, 2023
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)