Hypothyroidism
Conditions
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.
Interventions
Levothyroxine sodium 10 mg/mL
Sponsors
Xeris Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Countries
United States
Participant flow
Recruitment details
Participants were recruited over an approximate 7.5 month period at medical research centers with experience in hypothyroidism.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| XP-8121 All participants who received at least 1 dose of XP-8121 (100 to 1500 μg subcutaneous injection). | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Maintenance Period | Adverse Event | 1 |
| Maintenance Period | Inability to achieve an adequate replacement dosage | 1 |
| Maintenance Period | Inability to achieve a tolerable replacement dosage | 1 |
| Titration Period | Adverse Event | 1 |
| Titration Period | Inability to Achieve a tolerable replacement dosage | 3 |
Baseline characteristics
| Characteristic | XP-8121 |
|---|---|
| Age, Continuous | 54.5 years |
| Baseline Body Mass Index | 29.50 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Primary Hypothyroidism History | 46 Participants |
| Prior Daily Oral Levothyroxine Brand Other Brand or Generic | 37 Participants |
| Prior Daily Oral Levothyroxine Brand Synthroid | 9 Participants |
| Prior Daily Oral Levothyroxine Dose 100 micrograms | 8 Participants |
| Prior Daily Oral Levothyroxine Dose 112 micrograms | 3 Participants |
| Prior Daily Oral Levothyroxine Dose 125 micrograms | 3 Participants |
| Prior Daily Oral Levothyroxine Dose 150 micrograms | 2 Participants |
| Prior Daily Oral Levothyroxine Dose 175 micrograms | 1 Participants |
| Prior Daily Oral Levothyroxine Dose 50 micrograms | 14 Participants |
| Prior Daily Oral Levothyroxine Dose 75 micrograms | 12 Participants |
| Prior Daily Oral Levothyroxine Dose 88 micrograms | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 42 | 0 / 46 |
| other Total, other adverse events | 19 / 46 | 4 / 42 | 22 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 42 | 0 / 46 |
Outcome results
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.
Time frame: Day 29 of the Maintenance Period
Population: 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.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| XP-8121 | Dose Conversion Factor | 4.24 Ratio |
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.
Time frame: Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period
Population: 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 4 Dosing | 1 - Very Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 4 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 4 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 1 Dosing | 0 - None | 44 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 1 Dosing | 1 - Very Slight | 2 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 1 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 1 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 1 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 2 Dosing | 0 - None | 43 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 2 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 2 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 2 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 2 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 3 Dosing | 0 - None | 43 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 3 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 3 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 3 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 3 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 4 Dosing | 0 - None | 41 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 4 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 5 Dosing | 0 - None | 42 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 5 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 5 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 5 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 5 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 6 Dosing | 0 - None | 41 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 6 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 6 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 6 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 6 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 7 Dosing | 0 - None | 11 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 7 Dosing | 1 - Very Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 7 Dosing | 2 - Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 7 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 7 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 8 Dosing | 0 - None | 12 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 8 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 8 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 8 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Titration Period: Week 8 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 1 Dosing | 0 - None | 42 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 1 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 1 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 1 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 1 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 8 Dosing | 0 - None | 42 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 8 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 8 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 8 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 8 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 15 Dosing | 0 - None | 40 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 15 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 15 Dosing | 2 - Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 15 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 15 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 22 Dosing | 0 - None | 39 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 22 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 22 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 22 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Edema | Maintenance Period: Day 22 Dosing | 4 - Severe | 0 Participants |
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.
Time frame: Week 1 Dosing in Titration Period through Day 22 Dosing in Maintenance Period
Population: 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 1 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 8 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 8 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 1 Dosing | 0 - None | 40 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 1 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 1 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 1 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 8 Dosing | 0 - None | 40 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 8 Dosing | 1 - Very Slight | 2 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 8 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 8 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 8 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 1 Dosing | 0 - None | 43 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 1 Dosing | 1 - Very Slight | 3 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 1 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 1 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 2 Dosing | 0 - None | 41 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 2 Dosing | 1 - Very Slight | 2 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 2 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 2 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 2 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 3 Dosing | 0 - None | 41 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 3 Dosing | 1 - Very Slight | 2 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 3 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 15 Dosing | 0 - None | 39 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 15 Dosing | 1 - Very Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 15 Dosing | 2 - Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 22 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 15 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 15 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 22 Dosing | 0 - None | 37 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 22 Dosing | 1 - Very Slight | 2 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 22 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 22 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 8 Dosing | 1 - Very Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 8 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 3 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 3 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 4 Dosing | 0 - None | 37 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 4 Dosing | 1 - Very Slight | 5 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 4 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 4 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 4 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 5 Dosing | 0 - None | 38 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 5 Dosing | 1 - Very Slight | 4 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 5 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 5 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 5 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 6 Dosing | 0 - None | 38 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 6 Dosing | 1 - Very Slight | 3 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 6 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 6 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 6 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 7 Dosing | 0 - None | 12 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 7 Dosing | 1 - Very Slight | 1 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 7 Dosing | 2 - Slight | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 7 Dosing | 3 - Moderate | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 7 Dosing | 4 - Severe | 0 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Titration Period: Week 8 Dosing | 0 - None | 12 Participants |
| XP-8121 | Tolerability Assessment: Modified Draize Scale - Erythema | Maintenance Period: Day 1 Dosing | 1 - Very Slight | 2 Participants |
Primary
Tolerability Assessments: Injection Site Discomfort Evaluation
Injection site discomfort was assessed by each participant at 10 (+/-2) minutes post-injection.
Time frame: Week 1 dosing in the Titration Period through Day 22 dosing in the Maintenance Period
Population: 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.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 5 Dosing | No | 30 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 5 Dosing | Yes | 12 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 6 Dosing | Yes | 9 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 6 Dosing | No | 32 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 7 Dosing | Yes | 6 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 8 Dosing | Yes | 2 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 15 Dosing | No | 33 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 22 Dosing | Yes | 6 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 1 Dosing | Yes | 14 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 1 Dosing | No | 32 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 2 Dosing | Yes | 9 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 2 Dosing | No | 34 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 3 Dosing | Yes | 12 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 3 Dosing | No | 31 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 4 Dosing | Yes | 10 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 4 Dosing | No | 32 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 7 Dosing | No | 7 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Titration Period: Week 8 Dosing | No | 10 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 1 Dosing | Yes | 13 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 1 Dosing | No | 29 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 8 Dosing | Yes | 12 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 8 Dosing | No | 30 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 15 Dosing | Yes | 8 Participants |
| XP-8121 | Tolerability Assessments: Injection Site Discomfort Evaluation | Maintenance Period: Day 22 Dosing | No | 33 Participants |
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.
Time frame: Day 29 of the Maintenance Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XP-8121 | Proportion of Participants With Normalized TSH at End of Maintenance Period | 31 Participants |
| Participants Who Entered the Maintenance Period | Proportion of Participants With Normalized TSH at End of Maintenance Period | 31 Participants |
Secondary
Proportion of Participants With Normalized TSH Throughout the Maintenance Period
Proportion of participants enrolled with normalized TSH throughout the Maintenance Period
Time frame: Day 29 of the Maintenance Period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| XP-8121 | Proportion of Participants With Normalized TSH Throughout the Maintenance Period | 27 Participants |
| Participants Who Entered the Maintenance Period | Proportion of Participants With Normalized TSH Throughout the Maintenance Period | 27 Participants |
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
Time frame: Up to Day 29 of the Maintenance Period
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Baseline | 14.60 pmol/L | Standard Deviation 2.713 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 2 Dosing | 12.09 pmol/L | Standard Deviation 2.209 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 3 Dosing | 11.69 pmol/L | Standard Deviation 2.494 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 4 Dosing | 12.47 pmol/L | Standard Deviation 2.668 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 5 Dosing | 12.84 pmol/L | Standard Deviation 2.417 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 6 Dosing | 12.88 pmol/L | Standard Deviation 1.977 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 7 Dosing | 12.32 pmol/L | Standard Deviation 1.814 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Titration Period: Week 8 Dosing | 13.26 pmol/L | Standard Deviation 1.84 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Maintenance Period: Day 1 Dosing (Baseline) | 14.50 pmol/L | Standard Deviation 2.411 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Maintenance Period: Day 8 Dosing | 14.36 pmol/L | Standard Deviation 2.319 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Maintenance Period: Day 15 Dosing | 14.24 pmol/L | Standard Deviation 2.147 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Maintenance Period: Day 22 Dosing | 14.27 pmol/L | Standard Deviation 1.917 |
| XP-8121 | Thyroid Hormone Concentrations: Free Thyroxine (fT4) | Maintenance Period: Day 29 | 14.14 pmol/L | Standard Deviation 1.796 |
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
Time frame: Up to Day 29 of the Maintenance Period
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Baseline | 1.958 mIU/L | Standard Deviation 1.0778 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 2 Dosing | 3.942 mIU/L | Standard Deviation 2.8299 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 3 Dosing | 6.534 mIU/L | Standard Deviation 8.2589 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 4 Dosing | 6.162 mIU/L | Standard Deviation 8.8632 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 5 Dosing | 6.397 mIU/L | Standard Deviation 9.8016 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 6 Dosing | 5.506 mIU/L | Standard Deviation 7.1427 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 7 Dosing | 8.326 mIU/L | Standard Deviation 8.512 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Titration Period: Week 8 Dosing | 5.752 mIU/L | Standard Deviation 5.3967 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Maintenance Period: Day 1 Dosing (Baseline) | 2.967 mIU/L | Standard Deviation 2.1827 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Maintenance Period: Day 8 Dosing | 2.920 mIU/L | Standard Deviation 2.7009 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Maintenance Period: Day 15 Dosing | 2.739 mIU/L | Standard Deviation 2.8858 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Maintenance Period: Day 22 Dosing | 2.494 mIU/L | Standard Deviation 2.0766 |
| XP-8121 | Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH) | Maintenance Period: Day 29 | 2.493 mIU/L | Standard Deviation 1.5087 |
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
Time frame: Up to Day 29 of the Maintenance Period
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 6 Dosing | 97.38 nmol/L | Standard Deviation 22.056 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 7 Dosing | 90.29 nmol/L | Standard Deviation 18.867 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 8 Dosing | 88.58 nmol/L | Standard Deviation 25.032 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Maintenance Period: Day 1 Dosing (Baseline) | 103.45 nmol/L | Standard Deviation 24.97 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Maintenance Period: Day 8 Dosing | 102.24 nmol/L | Standard Deviation 23.704 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Baseline | 103.68 nmol/L | Standard Deviation 27.278 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 2 Dosing | 88.17 nmol/L | Standard Deviation 23.019 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 3 Dosing | 89.68 nmol/L | Standard Deviation 23.019 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 4 Dosing | 92.44 nmol/L | Standard Deviation 24.104 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Titration Period: Week 5 Dosing | 94.26 nmol/L | Standard Deviation 22.059 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Maintenance Period: Day 15 Dosing | 103.35 nmol/L | Standard Deviation 23.508 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Maintenance Period: Day 22 Dosing | 104.67 nmol/L | Standard Deviation 19.389 |
| XP-8121 | Thyroid Hormone Concentrations: Total Thyroxine | Maintenance Period: Day 29 | 101.97 nmol/L | Standard Deviation 24.532 |