XW014 for Type 2 Diabetes

Recruiting at 2 trial locations

Overseen By Eric Adegbite

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Sciwind Biosciences USA Co., Ltd.

Trial Summary

What is the purpose of this trial?

This is a Phase 1, randomized, double-blind, placebo-controlled, first-in-human (FIH) study to evaluate the safety, tolerability, food effect (FE), pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered XW014 in healthy participants and patients with T2DM. This study will consist of 4 parts: a Single Ascending Dose (SAD) part in healthy subjects (Part A), and Multiple Ascending Dose (MAD) parts in healthy subjects with elevated BMI (Part B and Part B-EXT) and patients with T2DM \[Optional\] (Part C).

Do I have to stop taking my current medications for the trial?

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

What data supports the idea that XW014 for Type 2 Diabetes is an effective drug?

The available research shows that exenatide once weekly (XW014) is effective for treating Type 2 Diabetes. In clinical trials, patients using XW014 experienced a reduction in their blood sugar levels by 1.5% to 1.9% and lost between 2 kg to 4 kg in weight. These results were consistent across different studies, indicating that XW014 helps improve blood sugar control and supports weight loss. Compared to other treatments like sitagliptin, pioglitazone, or insulin glargine, XW014 showed similar or better outcomes in managing diabetes. ^{1 2 3 4 5}

What safety data is available for the treatment XW014 for Type 2 Diabetes?

The research provided does not mention XW014 specifically, but it includes safety data on exenatide once weekly (QW), a GLP-1 receptor agonist used for Type 2 Diabetes. Studies show that exenatide QW has been evaluated for safety over periods of 3 to 6 years, with data indicating its safety and tolerability. The DURATION-7 study also compared exenatide QW to a placebo, providing additional safety insights. However, no direct safety data for XW014 is available in the provided research. ^{3 5 6 7 8}

Is the drug XW014 a promising treatment for Type 2 Diabetes?

The information provided does not mention XW014 specifically, so we cannot determine if it is a promising treatment for Type 2 Diabetes based on the given data. ^{5 9 10 11 12}

Research Team

Susan Xu, MD

Principal Investigator

Sciwind Biosciences

Eligibility Criteria

This trial is for healthy individuals and those with Type 2 Diabetes Mellitus (T2DM). Participants must be willing to consent, weigh over 50 kg, and be aged 18-70 years for Part A or 18-55 years for Parts B and C. T2DM patients should have had the condition for at least six months with an HbA1c level between 6.5% to 8.5%. People with uncontrolled hypertension, type 1 diabetes, significant active diseases, or a history of certain thyroid cancers are excluded.

Inclusion Criteria

I have had type 2 diabetes for over 6 months with an HbA1c between 6.5% and 8.5%.

I am willing and able to follow the study's requirements.

I am either male or female.

Exclusion Criteria

I don't have any health issues that could affect how my body handles the trial medication.

I or my family have a history of specific thyroid cancer or genetic conditions.

I have no significant active diseases affecting major body systems.

Treatment Details

Interventions

• Placebo (Drug)
• XW014 (Other)

Trial Overview The study tests XW014's safety and effects in humans when taken orally. It has three parts: one where healthy subjects take a single dose (SAD), another where overweight healthy subjects take multiple doses (MAD), and the last part involves T2DM patients taking multiple doses to see how their bodies react over time.

Participant Groups

Group I: MAD Cohort B-EXT - XW014 Active Control 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group II: MAD Cohort B-EXT - Placebo Active Control 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group III: MAD Cohort B - XW014 Active Control 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group IV: SAD Cohort A - XW014 Active Control 1 Intervention

Single oral XW014 administration

Group V: MAD Cohort C - XW014 Active Control 1 Intervention

MAD in Patients with T2DM

Group VI: MAD Cohort C - Placebo Placebo Group 1 Intervention

MAD in Patients with T2DM

Group VII: MAD Cohort B - Placebo Placebo Group 1 Intervention

MAD in Healthy Subjects with Elevated BMI

Group VIII: SAD Cohort A - Placebo Placebo Group 1 Intervention

Single oral placebo administration

Who Is Running the Clinical Trial?

Sciwind Biosciences USA Co., Ltd.

Lead Sponsor

Trials

3

Recruited

240+

Findings from Research

In a study of 5141 patients with type 2 diabetes, both exenatide once weekly (QW) and liraglutide showed similar effectiveness in reducing HbA1c levels and promoting weight loss over one year.

Insulin-naive patients with higher baseline HbA1c levels experienced greater reductions in HbA1c with both treatments, indicating that either medication can be a suitable option for managing diabetes while also aiding in weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis. McAdam-Marx, C., Nguyen, H., Schauerhamer, MB., et al.[2022]

GLP-1 receptor agonists, like exenatide once weekly (ExQW), effectively improve glycemic control in patients with type 2 diabetes mellitus (T2DM) without increasing the risk of hypoglycemia, showing consistent reductions in glycosylated hemoglobin by -1.5% to -1.9% and weight loss of -2 kg to -4 kg during clinical trials.

The clinical development of ExQW demonstrated safety and efficacy across various background treatments, with the majority of participants (68%) on metformin monotherapy, indicating its potential as a valuable addition to T2DM treatment algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide once-weekly clinical development: safety and efficacy across a range of background therapies. Stonehouse, A., Walsh, B., Cuddihy, R.[2022]

In a 6-year study involving 295 patients with type 2 diabetes, exenatide once weekly (QW) led to significant and sustained improvements in blood sugar levels, with a 1.6% reduction in HbA1c and notable weight loss of 4.2 kg.

The treatment was found to be safe, with no unexpected adverse events reported over 1202.4 patient-years, although minor hypoglycemia was more common when used alongside sulfonylureas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study. Henry, RR., Klein, EJ., Han, J., et al.[2022]

Once-weekly glucagon-like peptide 1 receptor agonists (QW GLP1RA) are a significant advancement in diabetes treatment, offering a new option for managing blood sugar levels.

This review discusses the pharmacology and clinical use of QW GLP1RA, emphasizing their potential benefits in diabetes management compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly glucagon-like peptide 1 receptor agonists. Kalra, S., Gupta, Y.[2018]

In a study of 464 patients with type 2 diabetes, adding exenatide once weekly to insulin therapy significantly reduced HbA1c levels by 0.73% compared to placebo, indicating improved blood sugar control.

Exenatide treatment also led to a reduction in body weight and postprandial glucose levels, with no increase in hypoglycaemia incidents, suggesting it is a safe and effective option for patients inadequately controlled on insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. Guja, C., Frías, JP., Somogyi, A., et al.[2022]

In a study involving 329 patients with type 2 diabetes, exenatide once weekly (QW) demonstrated sustained reductions in HbA1c, fasting glucose, and body weight over 3 years, indicating its long-term efficacy in managing diabetes.

Exenatide QW was well tolerated with no new safety concerns, and nearly half of the participants achieved HbA1c levels below 7.0%, showing its effectiveness compared to insulin glargine, which was associated with weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy and safety of exenatide once weekly: A pooled analysis of three trials. Trautmann, ME., Van Gaal, L., Han, J., et al.[2022]

A review of 30 Phase 3 clinical trials found that the most common side effects of once-weekly GLP-1 receptor agonists (dulaglutide, exenatide extended-release, and semaglutide) were mild-to-moderate gastrointestinal issues like nausea and diarrhea, which were generally transient.

The risk of serious adverse events such as hypoglycemia, pancreatitis, and diabetic retinopathy complications was low across the three GLP-1 RAs, although semaglutide showed a slightly higher rate of diabetic retinopathy events in one trial, likely due to rapid glucose control improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. Trujillo, J.[2021]

Vildagliptin, a DPP-4 inhibitor, has a safety and tolerability profile comparable to placebo, based on extensive clinical studies and real-world data involving patients with type 2 diabetes mellitus (T2DM).

The cumulative evidence from clinical development and post-marketing surveillance indicates that vildagliptin is a safe option for managing T2DM, with rare adverse drug reactions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance. Mathieu, C., Kozlovski, P., Paldánius, PM., et al.[2022]

A new class of DPP-4 inhibitors, derived from the xanthine scaffold, has been developed, with one compound (BI 1356) showing strong potential for lowering blood glucose levels in various animal models.

BI 1356 is currently in phase IIb clinical trials and may offer a once-daily oral treatment option for individuals with type 2 diabetes, highlighting its efficacy and convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. Eckhardt, M., Langkopf, E., Mark, M., et al.[2022]

Exenatide once weekly (ExeOW) significantly improves glycemic control in type 2 diabetes patients compared to other treatments, achieving reductions in HbA1c levels between -1.1% and -2.0% over 3-6 years.

ExeOW is well-tolerated, with benefits including moderate weight loss (2-4 kg) and low risk of hypoglycemia, making it a convenient long-term treatment option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Long-Term Efficacy, Tolerability, and Safety of Exenatide Once Weekly for Type 2 Diabetes. Genovese, S., Mannucci, E., Ceriello, A.[2022]

AC3174, an analog of exenatide, effectively lowers plasma glucose levels in both non-diabetic and diabetic mice, demonstrating similar potency to exenatide, with ED(50) values of 1.2 and 1.3 microg/kg respectively.

In addition to lowering glucose, AC3174 increases insulin levels and reduces food intake, indicating its potential as a glucoregulatory agent with multiple beneficial effects for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological activity of AC3174, a peptide analog of exendin-4. Hargrove, DM., Kendall, ES., Reynolds, JM., et al.[2019]

References

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

Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis. [2022]

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

Exenatide once-weekly clinical development: safety and efficacy across a range of background therapies. [2022]

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

Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study. [2022]

4. Pakistan pubmed.ncbi.nlm.nih.gov

Once-weekly glucagon-like peptide 1 receptor agonists. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. [2022]

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

Three-year efficacy and safety of exenatide once weekly: A pooled analysis of three trials. [2022]

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

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

A Human Glucagon-Like Peptide-1-albumin Recombinant Protein with Prolonged Hypoglycemic Effect Provides Efficient and Beneficial Control of Glucose Metabolism in Diabetic Mice. [2022]

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

8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. [2022]

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

A Review of the Long-Term Efficacy, Tolerability, and Safety of Exenatide Once Weekly for Type 2 Diabetes. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Biological activity of AC3174, a peptide analog of exendin-4. [2019]