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

NCT03718390 | Completed Early Phase 1

• 3 other identifiers: LYN-PLT-C-001ACTRN12618000991213CM8818
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Retention; Healthy

Outcome Measures

Primary Outcomes (5)

• Gastric retention assessed by Magnetic Resonance Imaging (MRI)

  Visualization of formulation/formulation components in the stomach by MRI

  Up to 9 Days post-dosing

• Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting based on spontaneous reports

  The number of confirmed gastrointestinal adverse events will be reported based on spontaneous adverse event reporting

  Through study completion, up to 6 months

• 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)

  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

  Through study completion, up to 6 months

• 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

  Examination and reporting of post-dosing bowel movements for blood; clinically significant abnormal findings will be reported as AE's.

  Through study completion, up to 6 months

• Safety and tolerability of four LYN-PLT modified release capsules and a placebo capsule collected from Adverse Event (AE) reporting

  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

  Through study completion, up to 6 months

Secondary Outcomes (3)

• Gastric retention assessed by abdominal ultrasound (U/S)

  Up to 9 Days post-dosing

• Confirm esophageal clearance of several MR capsules and a placebo capsule

  2 hours post dosing

• Physical Feature of Recovered Formulation Components

  Through study completion up to Day 29

Study Arms (5)

Sentinel Group 1 LYN-PLT

EXPERIMENTAL

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

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

Sentinel Group 2 LYN-PLT

EXPERIMENTAL

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

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

Group 3 LYN-PLT

EXPERIMENTAL

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

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

Group 4 LYN-PLT

EXPERIMENTAL

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

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

Group 5 LYN-PLT

EXPERIMENTAL

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.

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

Interventions

Formulation A DRUG

Formulation A (37/40A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation

Also known as: LYN-PLT Formulation A

Group 3 LYN-PLT; Group 4 LYN-PLT; Group 5 LYN-PLT; Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Formulation B DRUG

Formulation B (46/40A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation

Also known as: LYN-PLT Formulation B

Group 3 LYN-PLT; Group 4 LYN-PLT; Group 5 LYN-PLT; Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Formulation C DRUG

Formulation C (37/50A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation

Also known as: LYN-PLT Formulation C

Group 3 LYN-PLT; Group 4 LYN-PLT; Group 5 LYN-PLT; Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Formulation D DRUG

Formulation D (46/50A) of LYN-PLT containing less than 300 mg sucrose within the extended release formulation

Also known as: LYN-PLT Formulation D

Group 3 LYN-PLT; Group 4 LYN-PLT; Group 5 LYN-PLT; Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Formulation E DRUG

Placebo Capsule containing microcrystalline cellulose

Also known as: Placebo capsule

Group 3 LYN-PLT; Group 4 LYN-PLT; Group 5 LYN-PLT; Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Endoscopy PROCEDURE

Endoscopy at 2 hours post dosing

Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Magnetic Resonance Imaging PROCEDURE

MRI will be performed on specified days according to protocol

Also known as: MRI

Group 3 LYN-PLT; Group 4 LYN-PLT; Group 5 LYN-PLT; Sentinel Group 1 LYN-PLT; Sentinel Group 2 LYN-PLT

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lyndra Inc.: lead

Study Sites (1)

CMAX

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Interventions

D-Worm; Granuflex E; Endoscopy; Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Sepehr Shakib, MD

  CMAX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sealed opaque envelopes containing simple randomization via computerized sequence generation
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 14, 2018
• First Posted: October 24, 2018
• Study Start: June 25, 2018
• Primary Completion: September 15, 2018
• Study Completion: November 2, 2018
• Last Updated: February 26, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)