A Phase 1b Study of LAPS-Exendin in Subjects of Type 2 Diabetes Mellitus

Overseen By Hanmi Clinical

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hanmi Pharmaceutical Company Limited

Disqualifiers: Type 1 diabetes, Retinopathy, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks

44 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug LAPS-Exendin?

Research shows that Exendin-4, a component of LAPS-Exendin, can lower blood sugar levels by stimulating insulin release and delaying stomach emptying. It has also been found to reduce tumor growth in prostate cancer, suggesting potential benefits beyond blood sugar control. ^{1 2 3 4 5}

What safety data exists for LAPS-Exendin (GLP-1 receptor agonists)?

GLP-1 receptor agonists, like LAPS-Exendin, are generally safe but can cause side effects such as nausea, vomiting, and diarrhea. They have been linked to concerns about pancreatic and thyroid issues, but studies have not confirmed these risks. They do not typically cause low blood sugar unless combined with certain other diabetes medications. ^{6 7 8 9 10}

How does the drug LAPS-Exendin differ from other treatments for its condition?

LAPS-Exendin is unique because it acts as an agonist (activator) of the GLP-1 receptor, which helps lower blood sugar by stimulating insulin release, reducing glucagon (a hormone that raises blood sugar) secretion, and slowing down stomach emptying. This mechanism is different from other treatments that may not target the GLP-1 pathway or have such a comprehensive effect on blood sugar regulation. ^{3 4 5 11 12}

What is the purpose of this trial?

This trial is testing a new drug, HM11260C, in people with Type 2 Diabetes Mellitus. The study aims to see if this drug can help control blood sugar levels by slowing down how fast food leaves the stomach and improving insulin production. Researchers will also check how safe and acceptable the treatment is. An existing diabetes medication, liraglutide (Victoza), will be used for comparison.

Research Team

Hanmi Clinical

Principal Investigator

California, United States

Eligibility Criteria

Inclusion Criteria

History of type 2 diabetes

Body mass index (BMI) ≥18 to ≤45 kg/m2 at the Screening Visit

Use of approved methods of contraception

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different doses of HM11260C or liraglutide to assess effects on gastric emptying and beta-cell response

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

Treatment Details

Interventions

• LAPS-Exendin

Participant Groups

Group I: Cohort C Experimental Treatment 1 Intervention

The daily treatment with 0.6 mg Victoza will be up titrated to 1.2 mg

Group II: Cohort B Experimental Treatment 2 Interventions

The monthly treatment with 4 mg HM11260C or placebo will be up titrated to 16 mg

Group III: Cohort A Experimental Treatment 2 Interventions

The weekly treatment of the 6 mg HM11260C or placebo will be maintained

Who Is Running the Clinical Trial?

Hanmi Pharmaceutical Company Limited

Lead Sponsor

Trials

196

Recruited

62,100+

Young Choi

Hanmi Pharmaceutical Company Limited

Chief Medical Officer since 2023

PhD in Pharmacology from Yonsei University

Jae-Hyun Park

Hanmi Pharmaceutical Company Limited

Chief Executive Officer since 2024

MD from Seoul National University

Findings from Research

The GLP-1 antagonist exendin 9-39 effectively blocked the insulin-releasing effects of GLP-1 in both laboratory settings and in healthy volunteers, demonstrating its role in glucose regulation.

Infusion of exendin 9-39 led to higher postprandial glucose levels in subjects, indicating that GLP-1 is crucial for maintaining normal blood sugar levels after meals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Edwards, CM., Todd, JF., Mahmoudi, M., et al.[2022]

GLP-1 receptor agonists (GLP-1RAs) are effective in reducing A1C levels and promoting weight loss in patients with type 2 diabetes, while posing a minimal risk of hypoglycemia.

The article provides a comprehensive review of safety and tolerability data, particularly focusing on exenatide, the first approved GLP-1RA, including its comparative risks related to hypoglycemia and potential impacts on pancreatic, thyroid, and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists Utilizing Data from the Exenatide Clinical Trial Development Program. Peng, H., Want, LL., Aroda, VR.[2018]

A study analyzing 1,164 cases of hypoglycemia linked to glucagon-like peptide-1 receptor agonists (GLP-1RAs) found that lixisenatide had the strongest association with hypoglycemia, indicating a need for caution when prescribing this medication.

The median onset time for hypoglycemia after starting GLP-1RA treatment was 5 days, with a notable hospitalization rate of 56.08% and a fatality rate of 3.53%, highlighting the potential risks associated with these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglycemia following the use of glucagon-like peptide-1 receptor agonists: a real-world analysis of post-marketing surveillance data. Zhao, Z., Tang, Y., Hu, Y., et al.[2022]

In a pilot study involving 9 infants with congenital hyperinsulinism (K(ATP)HI), the GLP-1 receptor antagonist exendin-(9-39) significantly increased fasting blood glucose levels, indicating its potential to help manage hypoglycemia in these patients.

The study suggests that targeting the GLP-1 receptor could be a promising therapeutic approach for treating children with K(ATP)HI, as exendin-(9-39) effectively inhibited insulin secretion in response to amino acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel. Calabria, AC., Li, C., Gallagher, PR., et al.[2022]

Exendin (9-39) amide (Ex [9-39]) effectively blocks the insulin-releasing action of GLP-1, which is important for managing conditions like alimentary hypoglycaemia.

Importantly, Ex (9-39) does not interfere with insulin secretion triggered by nutrients, suggesting it can be safely used to target GLP-1 without affecting overall insulin control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance of succinic acid dimethyl ester insulinotropic action to exendin (9-39) amide. Cancelas, J., García-Martínez, JA., Villanueva-Peñacarrillo, ML., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Quantification of the Contribution of GLP-1 to Mediating Insulinotropic Effects of DPP-4 Inhibition With Vildagliptin in Healthy Subjects and Patients With Type 2 Diabetes Using Exendin [9-39] as a GLP-1 Receptor Antagonist. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists Utilizing Data from the Exenatide Clinical Trial Development Program. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Upper and/or lower gastrointestinal adverse events with glucagon-like peptide-1 receptor agonists: Incidence and consequences. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Adverse Effects of GLP-1 Receptor Agonists. [2020]

9. China pubmed.ncbi.nlm.nih.gov

Hypoglycemia following the use of glucagon-like peptide-1 receptor agonists: a real-world analysis of post-marketing surveillance data. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Resistance of succinic acid dimethyl ester insulinotropic action to exendin (9-39) amide. [2018]