Pharmacodynamics and Pharmacokinetics of Different Coated and Uncoated Formulations of Glucose Beads After Single and Multiple Dose Administration Under Fasting Conditions in Obese Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- GLP-1
研究概览
简要总结
The goal of this clinical study was to assess pharmacodynamics (PD) and pharmacokinetics (PK) of different Glucose beads formulations in obese healthy subjects under fasting condition. The study was designed in 2 parts.
Part 1 (single-dose) of the study was randomized, open label, five-treatment, five-period, five-sequence, crossover and single-centric. Treatment arms were three dosages of a coated Glucose beads formulation (47% w/w glucose/bead; 8 g [T1], 12 g [T2] and 16 g glucose [T3]), one uncoated Glucose beads formulation (47% w/w glucose/bead; 12 g glucose [T4]) and one coated Glucose beads formulation (60% w/w glucose/bead;12 g glucose [T5]).
Part 2 (multiple-dose) of the study was open label, one-treatment, one-period and single-centric. Treatment arm was coated Glucose beads formulation (12 g glucose [T2]).
详细描述
Twenty healthy obese subjects were planned for this study. Eligible subjects fulfilling the inclusion/ exclusion criteria and who had willing to give their informed consent were enrolled for screening examination and, if found eligible, enrolled in the study.
Before each hospitalization, on day -1, subjects with Real-Time Reverse Transcription-Polymerase Chain Reaction (rRT-PCR) tested negative for the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus were hospitalized. At the hospitalization examination physical examinations (weight), vital signs, pregnancy test for female subjects, alcohol breath test, as well as a check of adverse events, inclusion and exclusion criteria and restrictions were performed. Subjects were admitted to the clinical site at least 13 hours prior to the administration of investigational product in each treatment period.
During each treatment period the hospitalization period in the clinical unit was 13 hours before and up to 11 hours after investigational product administration. Part 1: Single dose After an overnight fasting of at least 10 hours the subjects was administered either 8 g glucose (T1), 12 g glucose (T2), 16 g glucose (T3) of the coated Glucose beads formulation (47%), the uncoated Glucose beads formulation (T4) containing 12 g glucose (47%) or the coated Glucose beads formulation (60% w/w glucose/bead; 12 g glucose [T5]) starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position.
17 blood samples was drawn for determination of glucagon-like polypeptide 1 (GLP-1) levels at the prescribed times pre-dose (-1.0 h, -0.5 and 0.0 h [within 5 minutes]) and 0.5, 1.0, 1.5. 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0. 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.
A fraction of one pre-dose sample (-1.0 h) before investigational product administration in treatment period I was also used to determine circulating concentration of microRNA (miRNA) 1983.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy obese, Caucasian, male and female subjects 18 - 55 years of age
- •Body mass index within the range of > 30.0 kg/m2
- •Waist circumference: men > 102 cm
- •women > 88 cm
- •Female subjects of childbearing potential agree to undergo pregnancy tests and to use an appropriate method of contraception (i.e. oral contraceptive steroids, intrauterine device, barrier method)
- •Findings within the range of clinical acceptability in medical history (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)
- •Findings within the range of clinical acceptability in physical examination (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)
- •Laboratory values within the normal range (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)
- •Normal ECG or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
- •Normal vital signs (normal blood pressure and heart rate measured under stabilised conditions at screening visit after at least 5 minutes of rest in sitting position) or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
- •Normal GI function, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
- •Willingness to undergo screening and follow-up examinations (i.e. physical examinations and laboratory investigations before and after the treatment periods)
- •Ability to comprehend subject information and willingness to sign the informed consent
排除标准
- •Gastrointestinal, hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the investigational product
- •Established diagnosis of type-1 or type-2 diabetes mellitus
- •Treatment with insulin, insulin secretagogues (sulfonylurea derivatives, glinides, GLP-1 agonists (exenatide, lixisenatide, glutides), or thiazolidinediones (glitazones)
- •Unexplained rise in blood glucose
- •Treatment for constipation (including but not limited to lactulose or any other form of stool softeners, laxatives) or diarrhea (including but not limited to pectins, loperamide etc.) or any other medication known to interfere with gastrointestinal transit time, such as e.g. metoclopramide, opioids, or gastric potential of hydrogen (pH) (including but not limited to antacids, H2-receptor antagonists, prazoles)
- •History of hypersensitivity to the investigational product or any related drugs or to any of the excipients
- •History or presence of any clinically significant cardiovascular, pulmonary, hepatobiliary, renal, hematological, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease, which the clinical investigator does not consider a disqualification for participation in the study
- •Known heart failure (Grade I to IV of New York Heart Association classification)
- •Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance < 60 mL/min and serum creatinine >180 μmol/L)
- •Unexplained serum creatine phosphokinase (CPK) > 3-times the upper limit of normal (ULN).
- •Subjects with a reason for CPK elevation may have the measurement repeated prior to randomization; a CPK retest > 3-times ULN leads to exclusion.
- •Clinically significant abnormal laboratory values
- •Clinically significant ECG findings
- •Clinically significant vital signs
- •Clinically significant illness or surgery within 4 weeks prior to dosing
- •Less than 14 days after last acute disease
- •Volunteers liable to orthostatic dysregulation, fainting, or blackouts
- •History of, or current compulsive alcohol abuse (more than a total of 10 drinks weekly whereby one drink corresponds to 500 ml beer, 200 ml wine or 50 g spirits); or regular exposure to other substances of abuse
- •Donation or loss of blood equal to or exceeding 500 ml during 90 days before the first administration of investigational product
- •Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C-virus (HCV)
- •Participation in another study with an experimental drug within at least 3 months (or within five elimination half-lives of the previous experimental drug, whichever is longer) before the first administration of investigational product
- •Any use of drug, prescribed or over the counter (OTC) (inclusive herbal remedies), within 2 weeks (or within six elimination half-lives of this medication, whichever is longer) prior to the first administration of investigational product except if this will not affect the outcome of the study in the opinion of the clinical investigator
- •Pregnant women (positive pregnancy test)
- •Lactating women
- •Failure to provide informed consent
- •Unwillingness or inability to comply with the study protocol or study-related procedures (e.g. difficulty to stay fasting, consume the standard meals, or swallow the beads formulations; difficult venous access)
- •Positive result of rRT-PCR test to detect infection with the new SARS-CoV-2 coronavirus
研究组 & 干预措施
SINGLE DOSE- TEST PRODUCT 1 (T1)
Oral coated beads 8 g glucose (content glucose/bead 47% w/w)
干预措施: Glucose 8 g coated beads (47% w/w) (Drug)
SINGLE DOSE- TEST PRODUCT 2 (T2)
Oral coated beads 12 g glucose (content glucose/bead 47% w/w)
干预措施: Glucose 12 g coated beads (47% w/w) (Drug)
SINGLE DOSE- TEST PRODUCT 3 (T3)
Oral coated beads 16 g glucose (content glucose/bead 47% w/w)
干预措施: Glucose 16 g coated beads (47% w/w) (Drug)
SINGLE DOSE- TEST PRODUCT 4 (T4)
Oral uncoated beads 12 g glucose
干预措施: Glucose 12 g uncoated beads (Drug)
SINGLE DOSE- TEST PRODUCT 5 (T5)
Oral coated beads 12 g glucose (content glucose/bead 60% w/w)
干预措施: Glucose 12 g coated beads (60% w/w) (Drug)
MULTIPLE DOSE- TEST PRODUCT 2 (T2)
Oral coated beads 12 g glucose (content glucose/bead 47% w/w)
干预措施: Glucose 12 g coated beads (47% w/w) (Drug)
结局指标
主要结局
GLP-1
时间窗: Day 1-3:- pre-dose (-1.0 hour, -0.5 hour and 0 hour). Day 4:- Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.
Part 2: Concentration at the end of the dosing interval at steady state (Cτ,ss)
次要结局
- Visual analogue scale appetite(Pre-dose (0 hour) and 2, 3, 4, 5, 6, 8 and 10 hours after investigational product administration.)
- Visual analogue scale stomach rumbles(Pre-dose (0 hour) and 2, 3, 4, 5, 6, 8 and 10 hours after investigational product administration.)
- Glucose levels(Day 1- Day 3:- Pre-dose (3 samples). Day 4:- Pre-dose (-1.0 hour, 0 hour [within 5 minutes]) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration.)