A Phase 2, Multicenter, Non-Randomized, Open-Label, Single Arm, Self-controlled Study of XP-8121 For the Treatment of Adult Subjects With Hypothyroidism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 6
- 主要终点
- Dose Conversion Factor
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
XP-8121
XP-8121 100 to 1500 μg subcutaneous injection
干预措施: levothyroxine sodium (Drug)
结局指标
主要结局
Dose Conversion Factor
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Thyroid Hormone Concentrations: Free Thyroxine (fT4)(Up to Day 29 of the Maintenance Period)
- Proportion of Participants With Normalized TSH at End of Maintenance Period(Day 29 of the Maintenance Period)
- Thyroid Hormone Concentrations: Total Thyroxine(Up to Day 29 of the Maintenance Period)
- Proportion of Participants With Normalized TSH Throughout the Maintenance Period(Day 29 of the Maintenance Period)
- Thyroid Hormone Concentrations: Thyroid Stimulating Hormone (TSH)(Up to Day 29 of the Maintenance Period)