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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| XP-8121 | Experimental | XP-8121 100 to 1500 μg subcutaneous injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| levothyroxine sodium | Drug | Levothyroxine sodium 10 mg/mL |
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Valentina Conoscenti, MD | Xeris Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ProSciento, Inc. | Chula Vista | California | 91911 | United States | ||
| Catalina Research Institute, L.L.C. |
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A total of 140 potential participants were screened, 46 participants were enrolled, and 94 potential participants were screen failures. The most common reasons for screen failure were fT4 and TSH outside of the normal range as required by the eligibility criteria.
Participants were recruited over an approximate 7.5 month period at medical research centers with experience in hypothyroidism.
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| ID | Title | Description |
|---|---|---|
| FG000 | XP-8121 | All participants who received at least 1 dose of XP-8121 (100 to 1500 μg subcutaneous injection). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Titration Period |
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| Maintenance Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | XP-8121 | All participants who received at least 1 dose of XP-8121 (100 to 1500 μg subcutaneous injection). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Completer Population used for this analysis is defined as all participants who completed the Maintenance Period and exhibited normalized TSH throughout the Maintenance Period while on a stable dose of XP-8121 for approximately 6 weeks. Participants with a reduced dose at any point during the Maintenance Period were not included in the Completer Population. | Posted | Geometric Least Squares Mean | 90% Confidence Interval | Ratio | Day 29 of the Maintenance Period |
From Screening through the End of Maintenance Visit (Day 29) or up to 14 (+/-2 days) after last dose of XP-8121 for participants who withdrew prematurely
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Titration Period | All participants who received at least 1 dose of XP-8121 (100 to 1500 μg subcutaneous injection) during the Titration Period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Valentina Conoscenti, MD | Xeris Pharmaceuticals, Inc. | 1-877-XERIS-37 | Clinicaltrials@xerispharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 7, 2023 | Jun 4, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 4, 2024 | Jun 4, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007037 | Hypothyroidism |
| ID | Term |
|---|---|
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D013974 | Thyroxine |
| ID | Term |
|---|---|
| D013963 | Thyroid Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D024322 | Amino Acids, Aromatic |
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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 |
| Montclair |
| California |
| 91763 |
| United States |
| Panax Clinical Research, LLC | Miami Lakes | Florida | 33014 | United States |
| American Research Corporation | San Antonio | Texas | 78215 | United States |
| Mt. Olympus Medical Research, LLC | Sugar Land | Texas | 77479 | United States |
| Rainier Clinical Research Center | Renton | Washington | 98057 | United States |
|
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Baseline Body Mass Index | Screening eligibility criteria required a BMI of 18 to 40 kg/m^2. | Median | Full Range | kg/m^2 |
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| Primary Hypothyroidism History | Count of Participants | Participants |
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| Prior Daily Oral Levothyroxine Brand | Count of Participants | Participants |
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| Prior Daily Oral Levothyroxine Dose | Count of Participants | Participants |
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| Primary | 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. | The number of participants at each timepoint is dependent on the number of participants dosed at each timepoint. The number of participants decreases in association with study withdrawal, with the exception of the reduction in the number of participants in Titration Periods Week 7 and Week 8 due to the number of participants that transitioned to the Maintenance Period after dosing at Week 6. | Posted | Count of Participants | Participants | Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period |
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| Primary | 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. | The number of participants at each timepoint is dependent on the number of participants dosed at each timepoint. The number of participants decreases in association with study withdrawal, with the exception of the reduction in the number of participants in Titration Periods Week 7 and Week 8 due to the number of participants that transitioned to the Maintenance Period after dosing at Week 6. | Posted | Count of Participants | Participants | Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period |
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| Primary | Tolerability Assessments: Injection Site Discomfort Evaluation | Injection site discomfort was assessed by each participant at 10 (+/-2) minutes post-injection. | The number of participants at each timepoint is dependent on the number of participants dosed at each timepoint. The number of participants decreases in association with study withdrawal, with the exception of the reduction in the number of participants in Titration Periods Week 7 and Week 8 due to the number of participants that transitioned to the Maintenance Period after dosing at Week 6. | Posted | Count of Participants | Participants | Week 1 dosing in the Titration Period through Day 22 dosing in the Maintenance Period |
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| Secondary | Proportion of Participants With Normalized TSH Throughout the Maintenance Period | Proportion of participants enrolled with normalized TSH throughout the Maintenance Period | Posted | Count of Participants | Participants | Day 29 of the Maintenance Period |
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| Secondary | 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. | Posted | Count of Participants | Participants | Day 29 of the Maintenance Period |
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| Secondary | 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 | The number of participants at each timepoint is dependent on the number of participants dosed at each timepoint. The overall number follows the decrease associated with study withdrawal, with the exception of the reduction in the number of participants in Titration Periods Week 7 and Week 8 due to the number of participants that transitioned to the Maintenance Period after dosing at Week 6. | Posted | Mean | Standard Deviation | nmol/L | Up to Day 29 of the Maintenance Period |
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| Secondary | 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 | The number of participants at each timepoint is dependent on the number of participants dosed at each timepoint. The overall number follows the decrease associated with study withdrawal, with the exception of the reduction in the number of participants in Titration Periods Week 7 and Week 8 due to the number of participants that transitioned to the Maintenance Period after dosing at Week 6. | Posted | Mean | Standard Deviation | pmol/L | Up to Day 29 of the Maintenance Period |
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| Secondary | 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 | The number of participants at each timepoint is dependent on the number of participants dosed at each timepoint. The overall number follows the decrease associated with study withdrawal, with the exception of the reduction in the number of participants in Titration Periods Week 7 and Week 8 due to the number of participants that transitioned to the Maintenance Period after dosing at Week 6. | Posted | Mean | Standard Deviation | mIU/L | Up to Day 29 of the Maintenance Period |
|
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| 0 |
| 46 |
| 0 |
| 46 |
| 19 |
| 46 |
| EG001 | Maintenance Period | All participants who received at least 1 dose of XP-8121 (100 to 1500 μg subcutaneous injection) during the Maintenance Period. Includes only includes those participants that completed the Titration Period and entered the Maintenance Period. | 0 | 42 | 0 | 42 | 4 | 42 |
| EG002 | Overall | Includes all participants that received XP-8121 (100 to 1500 μg subcutaneous injection) in both Titration and Maintenance Treatment Periods. | 0 | 46 | 0 | 46 | 22 | 46 |
| Injection site pain | General disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Temperature intolerance | General disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 26.0 | Non-systematic Assessment |
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| Weight increased | Investigations | MedDRA 26.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Non-systematic Assessment |
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The publication policy allows the Sponsor to submit a multi-center publication within 18-month period after the study is completed at all institutions. If it is not submitted within such 18-month period, an individual PI may furnish the Sponsor with a copy of any proposed publication or release at least 90 days in advance of the proposed submission or presentation. The Sponsor may review such proposed publication or release and may request a delay in publication of up to an additional 90 days.
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| 2 - Slight |
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| 3 - Moderate |
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| 4 - Severe |
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| Titration Period: Week 2 Dosing |
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| Titration Period: Week 3 Dosing |
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| Titration Period: Week 4 Dosing |
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| Titration Period: Week 5 Dosing |
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| Titration Period: Week 6 Dosing |
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| Titration Period: Week 7 Dosing |
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| Titration Period: Week 8 Dosing |
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| Maintenance Period: Day 1 Dosing |
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| Maintenance Period: Day 8 Dosing |
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| Maintenance Period: Day 15 Dosing |
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| Maintenance Period: Day 22 Dosing |
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| 2 - Slight |
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| 3 - Moderate |
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| 4 - Severe |
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| Titration Period: Week 2 Dosing |
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| Titration Period: Week 3 Dosing |
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| Titration Period: Week 4 Dosing |
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| Titration Period: Week 5 Dosing |
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| Titration Period: Week 6 Dosing |
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| Titration Period: Week 7 Dosing |
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| Titration Period: Week 8 Dosing |
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| Maintenance Period: Day 1 Dosing |
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| Maintenance Period: Day 8 Dosing |
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| Maintenance Period: Day 15 Dosing |
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| Maintenance Period: Day 22 Dosing |
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| Titration Period: Week 2 Dosing |
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| Titration Period: Week 3 Dosing |
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| Titration Period: Week 4 Dosing |
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| Titration Period: Week 5 Dosing |
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| Titration Period: Week 6 Dosing |
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| Titration Period: Week 7 Dosing |
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| Titration Period: Week 8 Dosing |
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| Maintenance Period: Day 1 Dosing |
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| Maintenance Period: Day 8 Dosing |
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| Maintenance Period: Day 15 Dosing |
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| Maintenance Period: Day 22 Dosing |
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| Titration Period: Week 3 Dosing |
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| Titration Period: Week 4 Dosing |
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| Titration Period: Week 5 Dosing |
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| Titration Period: Week 6 Dosing |
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| Titration Period: Week 7 Dosing |
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| Titration Period: Week 8 Dosing |
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| Maintenance Period: Day 1 Dosing (Baseline) |
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| Maintenance Period: Day 8 Dosing |
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| Maintenance Period: Day 15 Dosing |
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| Maintenance Period: Day 22 Dosing |
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| Maintenance Period: Day 29 |
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| Titration Period: Week 3 Dosing |
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| Titration Period: Week 4 Dosing |
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| Titration Period: Week 5 Dosing |
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| Titration Period: Week 6 Dosing |
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| Titration Period: Week 7 Dosing |
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| Titration Period: Week 8 Dosing |
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| Maintenance Period: Day 1 Dosing (Baseline) |
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| Maintenance Period: Day 8 Dosing |
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| Maintenance Period: Day 15 Dosing |
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| Maintenance Period: Day 22 Dosing |
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| Maintenance Period: Day 29 |
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| Titration Period: Week 3 Dosing |
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| Titration Period: Week 4 Dosing |
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| Titration Period: Week 5 Dosing |
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| Titration Period: Week 6 Dosing |
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| Titration Period: Week 7 Dosing |
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| Titration Period: Week 8 Dosing |
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| Maintenance Period: Day 1 Dosing (Baseline) |
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| Maintenance Period: Day 8 Dosing |
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| Maintenance Period: Day 15 Dosing |
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| Maintenance Period: Day 22 Dosing |
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| Maintenance Period: Day 29 |
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