Study to Evaluate Safety/Duration in Stomach of Extended Release Capsules in Healthy Adults

Lyndra

Status and phase: Completed; Early Phase 1

Conditions: Healthy; Gastric Retention

Treatments: Procedure: Endoscopy; Drug: Formulation B; Drug: Formulation E; Drug: Formulation D; Drug: Formulation C; Drug: Formulation A; Procedure: Magnetic Resonance Imaging

Study type: Interventional

Funder types: Industry

Identifiers

NCT03718390

CM8818 (Other Identifier)

ACTRN12618000991213 (Registry Identifier)

LYN-PLT-C-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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40 participants in 5 patient groups

Sentinel Group 1 LYN-PLT

Experimental group

Description:

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

Treatment:

Procedure: Magnetic Resonance Imaging

Drug: Formulation A

Drug: Formulation D

Drug: Formulation C

Procedure: Endoscopy

Drug: Formulation E

Drug: Formulation B

Sentinel Group 2 LYN-PLT

Experimental group

Description:

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

Treatment:

Procedure: Magnetic Resonance Imaging

Drug: Formulation A

Drug: Formulation D

Drug: Formulation C

Procedure: Endoscopy

Drug: Formulation E

Drug: Formulation B

Group 3 LYN-PLT

Experimental group

Description:

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

Treatment:

Procedure: Magnetic Resonance Imaging

Drug: Formulation A

Drug: Formulation D

Drug: Formulation C

Drug: Formulation E

Drug: Formulation B

Group 4 LYN-PLT

Experimental group

Description:

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

Treatment:

Procedure: Magnetic Resonance Imaging

Drug: Formulation A

Drug: Formulation D

Drug: Formulation C

Drug: Formulation E

Drug: Formulation B

Group 5 LYN-PLT

Experimental group

Description:

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.

Treatment:

Procedure: Magnetic Resonance Imaging

Drug: Formulation A

Drug: Formulation D

Drug: Formulation C

Drug: Formulation E

Drug: Formulation B