Diabete Type 2Phase 1/2NCT05268237
Safety, Tolerability and Preliminary Efficacy of Sublingual Liraglutide in Patients With Type 2 Diabetes Mellitus
A Phase 1/2 study testing Liraglutide in people with Diabete Type 2, run by Biolingus at 1 site in Hong Kong.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabete Type 2
- What is being tested?
- Liraglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteHong Kong
- Study dates
- 25 Apr 2023to Mar 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- 90 mmHg <systolic blood pressure <160 mmHg
- 40 mmHg <diastolic blood pressure <100 mmHg
- 40 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.
- Negative test for selected drugs of abuse at screening (does not include alcohol) and at admission (testing at admission does include alcohol breath test). A positive result may be verified by re-testing (up to one false positive result permitted) and may be followed up at the discretion of the PI.
- Females must be non-pregnant and non-lactating, and either surgically sterile for a minimum of 6 months (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective contraceptive method (oral contraceptives pills, long-acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device [IUD]) from screening until study completion, or be post-menopausal for ≥12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels (≥ 40 IU/mL) at screening for amenorrheic female subjects. Females who are abstinent from heterosexual intercourse will also be eligible.
- Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study.
- Males must be surgically sterile (>30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the subject and his partner must be surgically sterile (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from screening until study completion. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP), as per Inclusion Criterion #14. Male subjects whose female partner is post-menopausal, and subjects who are abstinent from heterosexual intercourse will also be eligible. Male subjects must agree to refrain from donating sperm from screening until study completion.
Who cannot join
- 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.
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- 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.
- Unstable hypo- or hyperthyroidism.
- Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome Type 2.
- Current or history of bulimia or anorexia nervosa.
- History of severe allergy (requiring hospital care), severe reaction to any drug, or any known or suspected allergies or sensitivities to the study drug constituents.
- Diagnosis with Type 1 Diabetes Mellitus (T1DM) or any previous episodes of diabetic ketoacidosis.
- History of or ongoing inflammatory bowel disease or diabetic gastroparesis.
- Severe hypoglycaemia resulting in seizure/unconsciousness/coma/hospitalization in the last 3 months before screening.
- Persistent hyperglycaemia not controlled by metformin/diet/exercise.
- Proliferative retinopathy, nephropathy or renal impairment (<60 mL/min as calculated by the CKD-EPI equation) if deemed clinically significant by the PI.
- Any other serious medical condition, or abnormality in clinical laboratory tests, that would preclude the subject's safe participation in and completion of the study or increase the expected risk of exposure to the investigational product (IP) or would be expected to interfere with the planned evaluations, in the judgment of the PI.
- Use of diabetes medication other than metformin at screening and between screening and Day 1 assessments.
- Any medication during the treatment period and within 14 days before first dosing unless permitted by the inclusion criteria or permitted at the discretion of the PI and when the intake is unlikely to interfere with insulin/glucose control.
- Use of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 [GLP-1] agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolenindiones, acarbose in the 3 months prior to study enrolment will not be permitted.
- Unwilling or unable to follow protocol requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
Clinical Trials Unit, Chinese University of Hong Kong
Hong Kong
Elaine Chow, MD
About this study
Official title: A Phase Ib/IIa, Single Ascending Dose Study of the Safety, Tolerability and Preliminary Efficacy of Sublingual Liraglutide in Patients With Type 2 Diabetes Mellitus
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).
Read the detailed description
This Phase Ib/IIa study of SL liraglutide will be conducted at the Phase 1 Clinical Trial Center, Prince of Wales Hospital, Hong Kong. Study subjects will be patients with T2DM who have not previously received liraglutide. The study seeks to document the utility of a SL formulation of the approved active ingredient liraglutide, currently marketed in a subcutaneous (SC) formulation as Victoza®.
- Conditions
- Diabete Type 2
- Being tested
- Liraglutide, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Sublingual or subcutaneous liraglutide
PlaceboDrug
Sublingual placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Liraglutide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, an average of 6 weeks
Secondary outcomes (8)
Peak Plasma Concentration (Cmax) for glucose
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Area under the plasma concentration versus time curve (AUC) for glucose
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Peak Plasma Concentration (Cmax) for C-peptide
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Peak Plasma Concentration (Cmax) for insulin
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Area under the plasma concentration versus time curve (AUC) for C-peptide
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Area under the plasma concentration versus time curve (AUC) for insulin
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Insulin secretion rate (ISR)
A secondary objective is to document the pharmacodynamic effect of SL liraglutide through a mixed meal tolerance test (MMTT) following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Serum concentration of liraglutide
A secondary objective is to determine the pharmacokinetics (PK) of SL-liraglutide in plasma following single ascending dosing in treated subjects.
Measured: 5 hours following administration of the study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2022
- Study start25 Apr 2023
- Primary completionDec 2025 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabete Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Biolingus
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chinese University of Hong Kong
- Responsible party
- Sponsor
- Investigators
- Elaine YK Chow, Principal investigator, Chinese University of Hong KongJuliana CN Chan, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05268237
- Sponsor's protocol ID
- BIOL-001
- Status last verified
- Feb 2025
- First submitted
- 16 Feb 2022
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual participant data with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/IIa, Single Ascending Dose Study of the Safety, Tolerability and Preliminary Efficacy of Sublingual Liraglutide in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT05268237
- Acronym / sponsor ID
- BIOL-001
- Conditions
- Diabete Type 2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- BiolingusIndustry (pharma, biotech, devices)
- Collaborators
- Chinese University of Hong Kong
- Study start
- 25 Apr 2023 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 7 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This Phase Ib/IIa study of SL liraglutide will be conducted at the Phase 1 Clinical Trial Center, Prince of Wales Hospital, Hong Kong. Study subjects will be patients with T2DM who have not previously received liraglutide. The study seeks to document the utility of a SL formulation of the approved active ingredient liraglutide, currently marketed in a subcutaneous (SC) formulation as Victoza®.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1: Open Label | Experimental | Drug: LiraglutidePart 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. |
| Part 2: Investigator blind | Experimental | Drug: Liraglutide, Drug: PlaceboPart 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiraglutideSublingual or subcutaneous liraglutide | Drug | Part 1: Open Label, Part 2: Investigator blind |
| PlaceboSublingual placebo | Drug | Part 2: Investigator blind |
Primary outcome
Incidence, nature and severity of adverse events
Time frame: Through study completion, an average of 6 weeks
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.
8 secondary outcomes
Peak Plasma Concentration (Cmax) for glucose
Time frame: 5 hours following administration of the study drug
Area under the plasma concentration versus time curve (AUC) for glucose
Time frame: 5 hours following administration of the study drug
Peak Plasma Concentration (Cmax) for C-peptide
Time frame: 5 hours following administration of the study drug
Peak Plasma Concentration (Cmax) for insulin
Time frame: 5 hours following administration of the study drug
Area under the plasma concentration versus time curve (AUC) for C-peptide
Time frame: 5 hours following administration of the study drug
Area under the plasma concentration versus time curve (AUC) for insulin
Time frame: 5 hours following administration of the study drug
Insulin secretion rate (ISR)
Time frame: 5 hours following administration of the study drug
Serum concentration of liraglutide
Time frame: 5 hours following administration of the study drug
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Individual participant dataSharing planned: No. There is no plan to share individual participant data with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Elaine YK Chow principal investigator
Chinese University of Hong Kong
Juliana CN Chan principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Liraglutide in people with Diabete Type 2, run by Biolingus at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elaine YK Chow (+852 35051642, e.chow@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence, nature and severity of adverse events (time frame: Through study completion, an average of 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2025.