A Multicentre, Randomised, Controlled, Observer-Blind Study to Evaluate Safety and Gastric Retention Properties of Modified Release Prototype Capsules (LYN-PLT) in Healthy Adults
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting
研究概览
简要总结
To assess how long extended release prototype capsule formulations stay in the stomach as determined by magnetic resonance imaging (MRI).
To evaluate the safety of several extended release capsule formulations (LYN-PLT) and a placebo capsule.
详细描述
This is a multicentre, observer blind, randomised, single dose study in healthy adult subjects.
The first 5 subjects enrolled into the study will be regarded as Dosing Group 1 (sentinel group) and assigned to each of the five available study formulations. Dosing of subjects in Dosing Groups 1 and 2 will be performed at the endoscopy centre. Dosing of subjects in Dosing Groups 3 through 5 will be performed at the clinical site.
Subjects remain in the inpatient unit for 7 days after dosing. During this time, subjects undergo intermittent imaging assessments for gastric retention (MRI and abdominal U/S), safety assessments and faecal collections for assessments of retrieved components and bowel movement characteristics.
Subjects return to the clinic on Days 10, 15, 22 and 29 (End of Study visit). Safety assessments will be performed at all visits. MRI, abdominal U/S and outpatient faecal collections may continue based on the clinical findings from subjects dosed with modified release capsule formulations. On Day 29, the subjects will undergo final safety assessments at the clinic and thereafter, will be discharged from the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sealed opaque envelopes containing simple randomization via computerized sequence generation
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects
- •Body mass index of 18.0 to 30.0 kg/meters-squared
- •Suitable scores for two swallowing questionnaires
- •Demonstrate normal swallowing and gastrointestinal passage for capsule, as assessed while undergoing imaging studies
- •Must provide written informed consent
排除标准
- •Participants who have previously been enrolled in this study
- •History of any drug or alcohol abuse in the past 2 years
- •Current smokers and those who have smoked within the past 12 months
- •Individuals with clinically significant medical history relating to the gastrointestinal tract and potential complications, thereof
- •Individuals with a positive test for HIV, hepatitis B or hepatitis C
- •Serious adverse reaction or serious hypersensitivity to components of the study formulations or patency capsule
- •Individuals who have received any experimental agent within 30 days (or 5 half-lives), whichever is longer, prior to the date of dosing
- •Individuals with contraindication to MRI imaging
- •Individuals with functional constipation, irritable bowel, or functional diarrhea, as evaluated by standardized questionnaire
- •Individuals with contraindications to elective X-ray based on known or expected radiation exposure
研究组 & 干预措施
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation A (Drug)
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation B (Drug)
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation C (Drug)
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation D (Drug)
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation E (Drug)
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Endoscopy (Procedure)
Sentinel Group 1 LYN-PLT
Sentinel dosing in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Magnetic Resonance Imaging (Procedure)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation A (Drug)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation B (Drug)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation C (Drug)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation D (Drug)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation E (Drug)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Endoscopy (Procedure)
Sentinel Group 2 LYN-PLT
Sentinel dosing (second) in endoscopy center of one of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Magnetic Resonance Imaging (Procedure)
Group 3 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind). and evaluation of gastric retention by MRI
干预措施: Formulation A (Drug)
Group 3 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind). and evaluation of gastric retention by MRI
干预措施: Formulation B (Drug)
Group 3 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind). and evaluation of gastric retention by MRI
干预措施: Formulation C (Drug)
Group 3 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind). and evaluation of gastric retention by MRI
干预措施: Formulation D (Drug)
Group 3 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind). and evaluation of gastric retention by MRI
干预措施: Formulation E (Drug)
Group 3 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind). and evaluation of gastric retention by MRI
干预措施: Magnetic Resonance Imaging (Procedure)
Group 4 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation A (Drug)
Group 4 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation B (Drug)
Group 4 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation C (Drug)
Group 4 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation D (Drug)
Group 4 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Formulation E (Drug)
Group 4 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI
干预措施: Magnetic Resonance Imaging (Procedure)
Group 5 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI.
干预措施: Formulation A (Drug)
Group 5 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI.
干预措施: Formulation B (Drug)
Group 5 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI.
干预措施: Formulation C (Drug)
Group 5 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI.
干预措施: Formulation D (Drug)
Group 5 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI.
干预措施: Formulation E (Drug)
Group 5 LYN-PLT
Dosing in clinic of two of each formulation (A, B, C, D, E) in a 1:1:1:1:1 ratio (centralized, randomized, observer blind) and evaluation of gastric retention by MRI.
干预措施: Magnetic Resonance Imaging (Procedure)
结局指标
主要结局
Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting
时间窗: Through study completion, up to 6 months
If abdominal pain occurs, a systematic algorithm to evaluate abdominal pain \[modified Structured Assessment of GastroIntestinal Symptoms (SAGIS)\] will be used. Clinically significantly abnormal findings will be reported as adverse events
Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting based on spontaneous reports
时间窗: Through study completion, up to 6 months
The number of confirmed gastrointestinal adverse events will be reported based on spontaneous adverse event reporting
Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting based on changes in examinations pre (Day 1) and post dosing (Days 4 and 7)
时间窗: Through study completion, up to 6 months
Clinically significant aggregate changes in vital signs, physical examinations and safety laboratory assessments (haematology, liver function tests, clinical chemistry panel) between pre-dose (Day 1) and post-dosing (Day 4 and 7) will be reported as AE's
Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting based on post dosing evaluation of bowel movements for blood
时间窗: Through study completion, up to 6 months
Examination and reporting of post-dosing bowel movements for blood; clinically significant abnormal findings will be reported as AE's.
Gastric retention assessed by Magnetic Resonance Imaging (MRI)
时间窗: Up to 9 Days post-dosing
Visualization of formulation/formulation components in the stomach by MRI
次要结局
- Confirm esophageal clearance of several MR capsules and a placebo capsule(2 hours post dosing)
- Gastric retention assessed by abdominal ultrasound (U/S)(Up to 9 Days post-dosing)
- Physical Feature of Recovered Formulation Components(Through study completion up to Day 29)