Gastric Retention, Healthy
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGFormulation A
Formulation A (37/40A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation
DRUGFormulation B
Formulation B (46/40A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation
DRUGFormulation C
Formulation C (37/50A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation
DRUGFormulation D
Formulation D (46/50A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation
DRUGFormulation E
Placebo Capsule containing microcrystalline cellulose
PROCEDUREEndoscopy
Endoscopy at 2 hours post dosing
PROCEDUREMagnetic Resonance Imaging
MRI will be performed on specified days according to protocol
Sponsors
Lyndra Inc.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sealed opaque envelopes containing simple randomization via computerized sequence generation
Intervention model description
A total of 40 eligible subjects participate in the Dosing and Observation period. The enrollment occurs in five Dosing Groups. Within each Dosing Group, subjects are randomized to receive either one of four LYN-PLT extended release capsules or a placebo capsule (8 per formulation).
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects 2. Body mass index of 18.0 to 30.0 kg/meters-squared 3. Suitable scores for two swallowing questionnaires 4. Demonstrate normal swallowing and gastrointestinal passage for capsule, as assessed while undergoing imaging studies 5. Must provide written informed consent
Exclusion criteria
1. Participants who have previously been enrolled in this study 2. History of any drug or alcohol abuse in the past 2 years 3. Current smokers and those who have smoked within the past 12 months 4. Individuals with clinically significant medical history relating to the gastrointestinal tract and potential complications, thereof 5. Individuals with a positive test for HIV, hepatitis B or hepatitis C 6. Serious adverse reaction or serious hypersensitivity to components of the study formulations or patency capsule 7. Individuals who have received any experimental agent within 30 days (or 5 half-lives), whichever is longer, prior to the date of dosing 8. Individuals with contraindication to MRI imaging 9. Individuals with functional constipation, irritable bowel, or functional diarrhea, as evaluated by standardized questionnaire 10. Individuals with contraindications to elective X-ray based on known or expected radiation exposure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting | 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 | 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) | 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 | 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) | Up to 9 Days post-dosing | Visualization of formulation/formulation components in the stomach by MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Confirm esophageal clearance of several MR capsules and a placebo capsule | 2 hours post dosing | For Group 1 and Group 2 via endoscopy |
| Physical Feature of Recovered Formulation Components | Through study completion up to Day 29 | Record the physical features, e.g. number of polymeric arms (if separate) or if attached to the core, of formulation components recovered from collected fecal specimens |
| Gastric retention assessed by abdominal ultrasound (U/S) | Up to 9 Days post-dosing | Visualization of formulation/formulation components in the stomach by U/S |
Countries
Australia
Outcome results
None listed