A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Multiple Oral Doses of SHP626 in Overweight and Obese Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology
研究概览
简要总结
This study will investigate the safety and tolerability of daily dosing regimens of SHP626 in overweight and obese adults.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 是
入选标准
- •Males that comply with any applicable contraceptive requirements or females of non-childbearing potential
- •No history of active or chronic disease other than that allowed by study (hypertension, hyperlipidemia and GERD or heartburn)
- •Has a body mass index of 25-35 kg/m2 with a body weight of greater than 140lbs (assessed at screening)
排除标准
- •No history of alcohol or substance abuse, including use of tobacco
- •No substantial changes in eating habits or exercise routine.
研究组 & 干预措施
SHP626
9/12 subjects -1x daily dose of 20mg for 12 days 9/12 subjects-1x daily dose of 40mg for 12 days 9/12 subjects-1x daily dose of 80mg for 12 days 9/12 subjects-1x daily dose of 120mg for 12 days or dose lower than 80mg for 12 days 9/12 subjects-1x daily dose of 160mg for 12 days or dose lower than 80mg for 12 days 9/12 subjects-2x daily dose of SHP626 (dose TBD) for 12 days 9/12 subjects-2x daily dose of SHP626 (dose TBD; lower or higher than cohort 6) for 12 days 9/12 subjects-1x or 2x daily dose of SHP626 in an escalating titration (doses TBD). Initial 3 days of SHP626 followed by an increased dose of SHP626 for 3 days and finally a further increase in dose of SHP626 for 6 days 9/12 subjects will take a 1x or 2x daily dose of SHP626 in escalating titration (doses TBD; lower or higher dose than cohort 8). Initial 3 days of SHP626 followed by an increased dose of SHP626 for 3 days and finally a further increase in dose of SHP626 for 6 days
干预措施: SHP626 (Drug)
Placebo
Three subjects per cohort will take a matched placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Hematology
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of investigational medicinal product (IMP) or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An adverse event (AE) that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Hematology parameters included evaluation of hemoglobin, hematocrit, red blood cells, platelets, white blood cell count; total and differential, neutrophils (absolute), eosinophils (absolute), monocytes (absolute), basophils (absolute) and lymphocytes (absolute).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Thyroid Hormone Panel
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Thyroid hormone panel parameters included evaluation of thyroid hormones (TSH \[thyroid stimulating hormone\]; T3 \[triiodothyronine\] and T4 \[thyroxine\]).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (12-lead)
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Twelve lead electrocardiogram parameters \[(heart rate (HR), PR, RR, QRS and QT intervals and information on T-wave morphology (normal/abnormal) and U-wave morphology (absent/normal or abnormal)\] were assessed.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Fat Soluble Vitamins (Vitamin A, D, & E)
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Fat soluble vitamin included vitamin A (serum retinol), vitamin D (serum 25-hydroxycholecalciferol) and vitamin E (serum alfa-tocopherol).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Lipid Panel
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Lipid panel parameters included evaluation of total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and low-density lipoprotein (LDL) cholesterol.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Coagulation
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Coagulation included international normalized ratio, activated partial thromboplastin time and prothrombin time.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Standard Chemistry
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Standard chemistry parameters included evaluation of sodium, potassium, glucose, blood urea nitrogen, creatinine, calcium, chloride, thyrotropin, thyroxine, tri-iodothyronine, phosphorus, protein, bicarbonate or carbon dioxide, albumin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, urate, beta-human chorionic gonadotropin and follicle-stimulating hormone levels. Participant with TEAE related to standard chemistry were reported with hepatic enzyme increase.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs)
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Urinalysis Parameters
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Urinalysis parameters included evaluation of pH, glucose, protein, nitrites, leukocyte esterase, occult blood, ketones, bilirubin and specific gravity levels.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE. Vital signs parameter included evaluation of orthostatic blood pressure, respiratory rate and body temperature.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Who Discontinued From the Study
时间窗: From the start of the study drug administration up to 9 days after the last dose of study drug administration
TEAEs were defined as events that either had a start date on or after the first dose of IMP or has a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of IMP. An AE that occurred more than 9 days after the date of the last dose of double-blind IMP was not counted as a TEAE.
次要结局
- Average Total Fecal Bile Acid (FBA) Concentration(Day -2 up to Day 14)
- Mean Serum 7- Alpha-hydroxy-4-cholesten-3-one (C4) Concentration(Day -1 to Day 15)
- Maximum Observed Plasma Concentration (Cmax) of Volixibat(Day 1 to Day 14)
- Number of Participants With Stool Hardness Using Bristol Stool Chart(Day -2 to Day 14)
- Area Under the Plasma Concentration-Time Curve (AUC) of Volixibat (SHP626)(Day 1 to Day 14)