Safety, Tolerability and Preliminary Efficacy of Sublingual Liraglutide in Patients With Type 2 Diabetes Mellitus

NCT05268237 | Recruiting Phase 1 DMC

• 1 other identifier: BIOL-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib/IIa, single ascending dose study of the safety, tolerability and preliminary efficacy of sublingual (SL) Liraglutide in patients with type 2 diabetes mellitus (T2DM).

Conditions

Diabete Type 2

Outcome Measures

Primary Outcomes (1)

• Incidence, nature and severity of adverse events

  The primary objective of the study is to evaluate the safety and tolerability of single ascending doses of SL liraglutide in subjects with Type II Diabetes Mellitus (T2DM), and the primary outcome measures are therefore the incidence, nature and severity of adverse events, including those that are serious, dose limiting or of special interest.

  Through study completion, an average of 6 weeks

Secondary Outcomes (8)

• Peak Plasma Concentration (Cmax) for glucose

  5 hours following administration of the study drug

• Area under the plasma concentration versus time curve (AUC) for glucose

  5 hours following administration of the study drug

• Peak Plasma Concentration (Cmax) for C-peptide

  5 hours following administration of the study drug

• Peak Plasma Concentration (Cmax) for insulin

  5 hours following administration of the study drug

• Area under the plasma concentration versus time curve (AUC) for C-peptide

  5 hours following administration of the study drug

Study Arms (2)

Part 1: Open Label

EXPERIMENTAL

Part 1 of the trial will utilise an open label, single ascending dose, repeated treatment design. It will involve 3 subjects, each of whom will receive three single ascending doses of SL liraglutide (3, 12, 30mg and subcutaneous (SC) liraglutide (active comparator) with a mixed meal tolerance test (MMTT), separated by 1 week washout between doses.

Drug: Liraglutide

Part 2: Investigator blind

EXPERIMENTAL

Part 2 of the trial will utilise an investigator-blind, sponsor open, placebo-controlled, randomised, repeated treatment study design. It will involve 12 subjects. Each subjects will receive one of three possible doses of SL-liraglutide (to be decided by the Safety Monitoring Committee following analysis of the results from Part 1), SL-placebo or SC liraglutide in a randomised order with MMTT separated by 1 week washout between doses.

Drug: Liraglutide; Drug: Placebo

Interventions

Liraglutide DRUG

Sublingual or subcutaneous liraglutide

Part 1: Open Label; Part 2: Investigator blind

Placebo DRUG

Sublingual placebo

Part 2: Investigator blind

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 18-65 years (inclusive)
• Body mass index (BMI) 18-35 kg/m2, inclusive
• Normal blood pressure or well managed hypertension (systolic blood pressure \<160mmHg, diastolic blood pressure \<100 mmHg)
• Confirmed diagnosis of T2DM (by repeated laboratory findings) for at least 1 year.
• Subjects under glycemic control on a stable dose of metformin (within the standard of care dose range up to 2 g daily) for at least 2 months prior to enrolment or those who manage their condition only by diet/exercise.
• For subjects on a stable dose of concomitant metformin for at least 2 months prior to enrolment, the subject's dose of metformin will be required to remain constant until at least the completion of MMTT on the final dosing day. Subjects whose concomitant glucose lowering medication changes during the dosing phase of the study will be discontinued and may be replaced.
• For subjects not in receipt of concomitant metformin for at least 2 months prior to enrolment, and who manage their condition only by diet/exercise, documentation of stable glycemic control under current condition management for at least 2 months prior to enrolment, as confirmed by HbA1c. For subjects who meet this criterion, no change in disease management is permitted until at least the completion of MMTT on the final dosing day. Any subject who requires a change in disease management, including initiation of any diabetes medication during the study, will be discontinued from the study and may be replaced.
• Fasting plasma glucose ≥5.6 mmol/L at screening
• HbA1c ≥6.5% and ≤9.0% at screening
• Vital signs after 10 minutes resting supine:
• mmHg \<systolic blood pressure \<160 mmHg
• mmHg \<diastolic blood pressure \<100 mmHg
• bpm \<heart rate \<100 bpm Duplicate assessments will be performed and the average of the two assessments of blood pressure will be used.
• Standard 12-lead ECG parameter results at screening, after 10 minutes resting in supine position, within 120 ms \<PR \<220 ms, QRS \<120 ms, QTcF ≤450 ms (males), QTcF ≤470 ms (females).
• No history of significant cardiovascular disease over the preceding 3 years or any other major disease other than T2DM and well managed hypertension, unless permitted at the discretion of the PI.

You may not qualify if:

• Pregnant or lactating, or intending to become pregnant within 30 days after last dose of study drug.
• Participation in a clinical trial within 30 days before enrolment; use of any experimental oral therapy within 30 days or 5 half-lives prior to enrolment, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to enrolment, whichever is greater. Subjects who have received an experimental therapy that has no half-life, such as a vaccine, should have completed that therapy at least 30 days prior to enrolment.
• Any vaccine 2 weeks prior to first study drug administration until 2 weeks after the last dose, with the exception of current seasonal influenza vaccination.
• Use of any weight loss agent within the preceding 4 weeks.
• Surgery or hospitalization during the 4 weeks prior to screening.
• Planned procedure or surgery during the study.
• Blood transfusion within 8 weeks prior to screening.
• Donation or loss of blood (excluding the volume of blood that will be drawn during screening procedures) as follows: ≥ 300 mL of blood within 30 days prior to study drug administration.
• Poor peripheral venous access.
• Alcohol and/or substance abuse or dependence within the past 2 years.
• Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g. myocardial infarction, angina pectoris, New York Heart Association Class II or more cardiac failure).
• History of pancreatitis
• History or presence of an abnormal ECG that is clinically significant in the PI's opinion and/or evidence of prior myocardial infarction within 2 years before screening.
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease, coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g. hypokalemia, hypomagnesemia, hypocalcaemia), or family history of sudden unexplained death or long QT syndrome.
• Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2 x or total bilirubin ≥ 1.5 x the upper limit of normal (ULN), which remains above these limits if retested due to a slightly elevated initial result or abnormalities in synthetic function tests that are judged by the PI to be clinically significant.

Sponsors & Collaborators

• Biolingus: lead
• Chinese University of Hong Kong: collaborator

Study Sites (1)

Clinical Trials Unit, Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Elaine YK Chow

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

• Juliana CN Chan

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elaine YK Chow

CONTACT

+852 35051642; e.chow@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study is being conducted in 2 parts. Part 1 is an open-label study with no requirements for randomisation or blinding. Part 2 is a placebo-controlled, observer blinded, partially randomised, repeated treatment double-blinded controlled trial with active comparator.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: March 7, 2022
• Study Start: April 25, 2023
• Primary Completion: December 1, 2025
• Study Completion: March 1, 2026
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)