A Phase 1b, Open-label, Partially Randomised Study to Assess Safety and Compare Pharmacokinetics of New Oral hPTH(1-34) Tablet Formulations vs. Oral EBP05 Tablets and Subcutaneous Forteo® Injection in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Vital Signs - blood pressure (systolic/diastolic mmHg)
研究概览
简要总结
The purpose of this study is to characterize and compare the pharmacokinetics of hPTH(1 34) after treatment with modified oral formulations (EBP11, EBP11-F1, EBP11-F2, EBP11-F4, EBP11-F5 and EBP22) versus three dose levels of Entera Bio's extensively studied oral EBP05 1.5 mg, 2.5 mg and 3.0 mg as well as the commercial Forteo 0.02 mg subcutaneous injection.
详细描述
Stated in summary, eligibility criteria and outcome measures
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects, 18 - 35 years of age, inclusive, at screening.
- •Continuous nonsmoker who has not used nicotine containing products (including e-cigarettes, vapors, etc.) for at least 12 months prior to first dosing and throughout the study, based on subject self-reporting.
- •Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
- •Medically healthy with no clinically significant medical condition, physical examination, laboratory profiles, vital signs, orthostatic vital sign measurements, or ECGs, as deemed by the PI or designee to be relevant to the study and does not pose an additional risk to the subject by their participation in the study.
- •Understands the study procedures described in the Informed Consent Form (ICF), be willing and able to comply with the protocol, and provides written consent.
排除标准
- •History or current condition of mental instability or cognitive impairment that, in the opinion of the investigator, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures.
- •Active gastrointestinal inflammatory disorder, gastrointestinal motility disorders, and chronic gastritis, including but not limited to: ulcerative colitis, Crohn's disease, irritable bowel syndrome, short bowel syndrome, celiac disease, gastroparesis, that may affect drug bioavailability.
- •Any conditions or factors that, in the judgment of the PI or designee, somehow may impact gastrointestinal absorption, distribution or metabolism of parathyroid hormone analogues, or known to potentiate or predispose to undesired effects.
- •History of significant gastrointestinal, liver or kidney disease, or gastrointestinal surgery (including bariatric surgery, or any other interventional procedures with stomach and intestinal tract) that may affect either drug bioavailability, or hPTH(1-34) or SNAC metabolism.
- •History or presence of alcohol or drug abuse or positive urine drug or blood alcohol results at screening.
- •Known allergies or sensitivities to components of the Study Medication (e.g. soy) or known hypersensitivity to PTH or hPTH(1-34).
- •History or presence of clinically significant:
- •Urolithiasis;
- •Angina at Screening, in the opinion of the PI;
- •Hypocalcemia or hypercalcemia at screening;
- •Personal or family history of congenital long QT syndrome or known family history of sudden death.
- •Subjects with ECG findings deemed abnormal with clinical significance by the PI or designee at screening for the following:
- •QTcF interval > 470 msec;
- •PR > 220 msec;
- •QRS > 120 msec.
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- •Seated blood pressure is less than 90 systolic or 40 diastolic mmHg or greater than 140 systolic or 90 diastolic mmHg at screening;
- •Orthostatic vital sign results with a decrease in systolic > 20 mmHg or decrease in diastolic > 10 mm Hg, and/or increase in heart rate of > 20 beats per minute at screening or Day 1 check-in.
- •Seated heart rate is lower than 50 bpm or higher than 99 bpm at screening (when clinically significant as determined by PI).
- •Estimated creatinine clearance < 80 mL/min at screening
- •Unable to refrain from or anticipates the use of:
- •Any drug, including prescription and nonprescription medications, herbal remedies, or vitamin supplements that should be taken on the treatment visit day before the dosing of Study Medication and 2 hours after the dosing of Study Medication.
- •H2 blocker or PPI or antacid (including prescription and nonprescription) three days before the dosing of the Study Medication and 2 hours after the dosing of Study Medication.
- •Donation of blood or significant blood loss within 56 days prior to first dosing.
- •Hemoglobin levels below 13 g/dL at screening or at in screening test done during the study.
- •Plasma donation within 7 days prior to first dosing.
- •Participation in another interventional clinical study within 30 days prior to screening visit.
研究组 & 干预措施
Treatment A EBP05 2.5 mg
Single dose of oral EBP05 2.5 mg
干预措施: EBP05 (Drug)
Treatment B EBP05 1.5 mg
Single dose of oral EBP05 1.5 mg
干预措施: EBP05 (Drug)
Treatment C Forteo 0.02 mg
Single SC injection of Forteo 0.02 mg
干预措施: Forteo 0.02 mg (Drug)
Treatment D EBP11 1.5 mg
Single dose of oral EBP11 1.5 mg
干预措施: EBP11 (Drug)
Treatment E EBP11 BID (dose determined after IA)
BID administration of oral EBP11 2.5 mg tablets
干预措施: EBP11 (Drug)
Treatment F EBP11 BID (dose determined after IA)
BID administration of oral EBP11 tablets 1.5 mg tablets (3 x 0.5 mg tablets) as first dose and 2.5 mg (5 x 0.5 mg tablets) as second dose.
干预措施: EBP11 (Drug)
Treatment G EBP11 1.5 mg
Single dose of oral EBP11 1.5 mg
干预措施: EBP11 (Drug)
Treatment I EBP22 1.5 mg
Single dose of oral EBP22 1.5 mg
干预措施: EBP22 (Drug)
Treatment J EBP22 1.5 mg
Single dose of oral EBP22 1.5 mg
干预措施: EBP22 (Drug)
Treatment K EBP05 1.5 mg
Single dose of oral EBP05 1.5 mg
干预措施: EBP05 (Drug)
Treatment L EBP05 2.5 mg
Single dose of oral EBP05 2.5 mg
干预措施: EBP05 (Drug)
Treatment M Forteo 0.02 mg
Single SC injection of Forteo 0.02 mg
干预措施: Forteo 0.02 mg (Drug)
Treatment N EBP05 3.0 mg
Single dose of oral EBP05 3.0 mg
干预措施: EBP05 (Drug)
Treatment P EBP11-F2 1.5 mg
Single dose of oral EBP11-F2 1.5 mg
干预措施: EBP11-F2 (Drug)
Treatment Q EBP11-F4 2.5 mg
Single dose of oral EBP11-F4 2.5 mg
干预措施: EBP11-F4 (Drug)
Treatment R EBP11-F5 3.0 mg
Single dose of oral EBP11-F5 3.0 mg
干预措施: EBP11-F5 (Drug)
Treatment S EBP11-F1 1.0 mg
Single dose of oral EBP11-F1 1.0 mg
干预措施: EBP11-F1 (Drug)
Treatment H EBP22 2.5 mg (5 x 0.5 mg tablets)
Single dose of oral EBP22 2.5 mg (5 x 0.5 mg tablets)
干预措施: EBP22 (Drug)
Treatment O EBP11-F4 2.5 mg
Single dose of oral EBP11-F4 2.5 mg
干预措施: EBP11-F4 (Drug)
结局指标
主要结局
Vital Signs - blood pressure (systolic/diastolic mmHg)
时间窗: 6 hours
Safety parameter (group mean at each time point up to 360 min. post dose)
Assessment of the pharmacokinetic profile of plasma hPTH(1-34) after single or twice daily oral administration for treatment regimen as listed under Arms and Interventions at 5, 10, 15, 20, 40, 50, 60, 75, 90, 105, 120, 180, 240, 360 min. post dose
时间窗: 6 hours
Pharmacokinetic parameter - plasma hPTH(1-34) in pg/mL
Calculation of plasma levels of hPTH(1-34) AUC0-t for each treatment regimen
时间窗: 6 hours
Pharmacokinetic parameter - total drug exposure at different time points up to 360 min. post dose
Calculation of plasma levels of hPTH(1-34) AUC%extrap for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - Percent of AUC0-inf extrapolated to confirm reliability
Calculation of plasma levels of hPTH(1-34) Cmax for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - hPTH (1-34) maximal concentration in pg/mL (Cmax)
Calculation of plasma levels of hPTH(1-34) Tlast for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - time of the last measurable concentration of hPTH(1-34) in minutes
Calculation of dose proportionality for hPTH(1-34) for relevant treatment regimen
时间窗: 6 hours
Pharmacokinetic parameter
Incidence of Treatment-Emergent Adverse Events as assessed by the Principle Investigator
时间窗: 6-14 hours
Safety parameter - AEs observed over duration of study participation
Incidence of Serious Adverse Events (SAEs) as assessed by the Principle Investigator
时间窗: 6-14 hours
Safety parameter - SAEs observed over duration of study participation
Calculation of plasma levels of hPTH(1-34) AUC0-inf for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - total drug exposure in pg/mL over time from 0 extrapolated to infinity
Calculation of plasma levels of hPTH(1-34) Tmax for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - time in minutes to reach max. concentration of hPTH(1-34)
Calculation of plasma levels of hPTH(1-34) Kel for each treatment regimen
时间窗: 6 hours
Pharmacokinetic parameter - elimination rate constant in pg/mL, fraction of drug eliminated per time-point up to 360 min. post dose
Calculation of plasma levels of hPTH(1-34) t½ for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - terminal elimination half life of hPTH(1-34) in minutes
Assessment of inter-subject variability of hPTH(1-34) for each treatment regimen
时间窗: 6-14 hours
Pharmacokinetic parameter - Coefficient of Variance (CV%) of hPTH (1-34)
Assessment of the duration of exposure to hPTH(1-34) in minutes
时间窗: 6 hours
Pharmacokinetic parameter - up to 360 min. post dose
Vital Signs - body temperature (Celsius)
时间窗: 6 hours
Safety parameter (group mean at each time point up to 360 min. post dose)
Vital Signs - respiratory rate (breaths per minute)
时间窗: 6 hours
Safety parameter (group mean at each time point up to 360 min. post dose)
Vital Signs - heart rate (beats per minute)
时间窗: 6 hours
Safety parameter (group mean at each time point up to 360 min. post dose)
次要结局
未报告次要终点