HypothyroidismPhase 2NCT05823012

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

A Phase 2 study testing levothyroxine sodium in people with Hypothyroidism, run by Xeris Pharmaceuticals at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Hypothyroidism
What is being tested?: levothyroxine sodium
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: 6 sitesUnited States
Study dates: 15 May 2023to 22 Feb 2024
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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).

Who cannot join

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.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

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

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions: Hypothyroidism
Being tested: levothyroxine sodium
Medical subject headings: Hypothyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

levothyroxine sodiumDrug
Also called XP-8121
Levothyroxine sodium 10 mg/mL

Study groups in NCT05823012
Study group	Role	What they receive
XP-8121	Experimental	XP-8121 100 to 1500 μg subcutaneous injection Receives: Drug: levothyroxine sodium

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Proportion of participants enrolled with normalized TSH throughout the Maintenance Period
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Up to Day 29 of the Maintenance Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 May 202322 Feb 2024

First posted21 Apr 2023
Study start15 May 2023
Primary completion22 Feb 2024
Study completion22 Feb 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HypothyroidismStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05823012
Sponsor's protocol ID: XP-8121-120
Status last verified: Jul 2025
First submitted: 28 Mar 2023
Last updated: 3 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Comparison of Two Timings of Levothyroxine Intake in Hypothyroid Patients: A Cross-over Randomized Control Trial
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Understanding the Subnormal Rescue ofNeurological Development in Congenital Hypothyroidism (2022E5SZEM)
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All Hypothyroidism trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Multicenter, Non-Randomized, Open-Label, Single Arm, Self-controlled Study of XP-8121 For the Treatment of Adult Subjects With Hypothyroidism
ClinicalTrials.gov ID: NCT05823012
Acronym / sponsor ID: XP-8121-120
Conditions: Hypothyroidism
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Xeris PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 15 May 2023 (actual)
Primary completion: 22 Feb 2024 (actual)
Study completion: 22 Feb 2024 (actual)
First posted: 21 Apr 2023 (actual)
Results: Posted 3 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
XP-8121	Experimental	Drug: levothyroxine sodiumXP-8121 100 to 1500 μg subcutaneous injection

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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).

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
levothyroxine sodiumAlso: XP-8121Levothyroxine sodium 10 mg/mL	Drug	XP-8121

Primary outcome

Dose Conversion Factor
Time frame: 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
Time frame: 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 Assessment: Modified Draize Scale - Edema
Time frame: 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
Time frame: 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.

5 secondary outcomes

Proportion of Participants 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
Time frame: Day 29 of the Maintenance Period
Thyroid Hormone Concentrations: Total Thyroxine
Time frame: Up to Day 29 of the Maintenance Period
Thyroid Hormone Concentrations: Free Thyroxine (fT4)
Time frame: Up to Day 29 of the Maintenance Period
Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH)
Time frame: Up to Day 29 of the Maintenance Period

Results and safety

Results posted to the registry on 3 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
XP-8121	46	42

Primary outcome: Dose Conversion Factor

Time frame: Day 29 of the Maintenance Period. Geometric least squares mean (90% Confidence Interval). Unit: Ratio

Measure	XP-8121 n = 23
Value	4.24 (4.06 to 4.42)

Population analysed: 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.

Primary outcome: Tolerability Assessment: Modified Draize Scale - Erythema

Time frame: Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period. Count of participants. Unit: Participants

Measure	XP-8121 n = 46
Titration Period: Week 1 Dosing: 0 - None	43
Titration Period: Week 1 Dosing: 1 - Very Slight	3
Titration Period: Week 1 Dosing: 2 - Slight	0
Titration Period: Week 1 Dosing: 3 - Moderate	0
Titration Period: Week 1 Dosing: 4 - Severe	0
Titration Period: Week 2 Dosing: 0 - None	41
Titration Period: Week 2 Dosing: 1 - Very Slight	2
Titration Period: Week 2 Dosing: 2 - Slight	0

Population analysed: 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.

Primary outcome: Tolerability Assessment: Modified Draize Scale - Edema

Time frame: Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period. Count of participants. Unit: Participants

Measure	XP-8121 n = 46
Titration Period: Week 1 Dosing: 0 - None	44
Titration Period: Week 1 Dosing: 1 - Very Slight	2
Titration Period: Week 1 Dosing: 2 - Slight	0
Titration Period: Week 1 Dosing: 3 - Moderate	0
Titration Period: Week 1 Dosing: 4 - Severe	0
Titration Period: Week 2 Dosing: 0 - None	43
Titration Period: Week 2 Dosing: 1 - Very Slight	0
Titration Period: Week 2 Dosing: 2 - Slight	0

Primary outcome: Tolerability Assessments: Injection Site Discomfort Evaluation

Time frame: Week 1 dosing in the Titration Period through Day 22 dosing in the Maintenance Period. Count of participants. Unit: Participants

Measure	XP-8121 n = 46
Titration Period: Week 1 Dosing: Yes	14
Titration Period: Week 1 Dosing: No	32
Titration Period: Week 2 Dosing: Yes	9
Titration Period: Week 2 Dosing: No	34
Titration Period: Week 3 Dosing: Yes	12
Titration Period: Week 3 Dosing: No	31
Titration Period: Week 4 Dosing: Yes	10
Titration Period: Week 4 Dosing: No	32

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Titration Period	0 of 46 (0%)	19 of 46 (41.3%)	0 of 46
Maintenance Period	0 of 42 (0%)	4 of 42 (9.5%)	0 of 42
Overall	0 of 46 (0%)	22 of 46 (47.8%)	0 of 46

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Hypothyroidism

Not yet recruitingObservational study
Validation of Uzbek SARC-F and IPAQ-SF Questionnaires in Adults With and Without Hypothyroidism
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RecruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Valentina Conoscenti, MD study director

Xeris Pharmaceuticals, Inc.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing levothyroxine sodium in people with Hypothyroidism, run by Xeris Pharmaceuticals at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Conversion Factor (time frame: Day 29 of the Maintenance Period). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05823012.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.