Study of XP-8121 For the Treatment of Adult Subjects With Hypothyroidism
- Registration Number
- NCT05823012
- Lead Sponsor
- Xeris Pharmaceuticals
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
- 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).
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description XP-8121 levothyroxine sodium XP-8121 100 to 1500 μg subcutaneous injection
- Primary Outcome Measures
Name Time Method Dose Conversion Factor Day 29 of the Maintenance Period 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.
Tolerability Assessment: Modified Draize Scale - Erythema Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period 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.
Tolerability Assessments: Injection Site Discomfort Evaluation Week 1 dosing in the Titration Period through Day 22 dosing in the Maintenance Period Injection site discomfort was assessed by each participant at 10 (+/-2) minutes post-injection.
Tolerability Assessment: Modified Draize Scale - Edema Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period 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.
- Secondary Outcome Measures
Name Time Method Thyroid Hormone Concentrations: Free Thyroxine (fT4) Up to Day 29 of the Maintenance Period 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
Proportion of Participants With Normalized TSH at End of Maintenance Period Day 29 of the Maintenance Period Proportion of participants enrolled with normalized TSH at the end of the Maintenance Period.
Thyroid Hormone Concentrations: Total Thyroxine Up to Day 29 of the Maintenance Period 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
Proportion of Participants With Normalized TSH Throughout the Maintenance Period Day 29 of the Maintenance Period Proportion of participants enrolled with normalized TSH throughout the Maintenance Period
Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) Up to Day 29 of the Maintenance Period 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
Trial Locations
- 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
Mt. Olympus Medical Research, LLC
🇺🇸Sugar Land, Texas, United States
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
ProSciento, Inc.🇺🇸Chula Vista, California, United States