Avexitide for Hypoglycemia

(LUCIDITY Trial)

Recruiting at 22 trial locations

Overseen By Amylyx Clinical Trials Team

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amylyx Pharmaceuticals Inc.

Must not be taking: Insulin, GLP-1 agonists, Metformin, others

Disqualifiers: Insulinoma, Active psychiatric disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 16 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests avexitide for individuals experiencing frequent low blood sugar (hypoglycemia) after Roux-en-Y gastric bypass surgery. The goal is to determine if avexitide is safe and effective in reducing these low blood sugar events compared to a placebo. Participants will first undergo a screening and trial preparation period, then receive either avexitide or a placebo for 16 weeks. This will be followed by a transition to open-label treatment, where everyone will eventually receive avexitide. Those who have undergone gastric bypass surgery and experience recurring low blood sugar episodes may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that alter glucose metabolism or promote weight loss before starting, such as insulin, metformin, and GLP-1 agonists. You also need to avoid drugs that interfere with the study's sensor, like high doses of acetaminophen.

Is there any evidence suggesting that avexitide is likely to be safe for humans?

Research has shown that avexitide is generally easy for people to tolerate. In previous studies, participants who took avexitide experienced few serious side effects, indicating a good safety record. One study found that avexitide was well-tolerated over 28 days, with improvements in health. Another study observed that patients did not need extra help to manage their blood sugar levels while using avexitide.

These findings suggest that avexitide is safe for humans, but it's important to remember that all medicines can have side effects. Prospective participants should ask the trial team any questions about safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypoglycemia?

Avexitide is unique because it targets the underlying cause of hypoglycemia by blocking the hormone glucagon-like peptide-1 (GLP-1) receptor, which is different from standard treatments like dietary changes, glucose tablets, or medications that primarily focus on raising blood sugar levels directly. This new mechanism of action allows Avexitide to stabilize blood sugar more effectively and prevent sudden drops. Researchers are excited about Avexitide because it offers a promising new approach with the convenience of a once-daily subcutaneous injection, which could improve the quality of life for those struggling with hypoglycemia.

What evidence suggests that avexitide might be an effective treatment for post bariatric hypoglycemia?

Research has shown that avexitide, which participants in this trial may receive, can help reduce episodes of low blood sugar in people with post-bariatric hypoglycemia (PBH), especially after Roux-en-Y gastric bypass surgery. In earlier studies, avexitide reduced moderate low blood sugar episodes by 40% with a lower dose and by 55% with a higher dose. These studies found significant improvements, and patients tolerated the treatment well. Avexitide has consistently improved health measures, making it a promising option for managing PBH. ^{1 2 6 7 8}

Who Is on the Research Team?

Amylyx Medical Director

Principal Investigator

Amylyx Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a BMI up to 40 who've had Roux-en-Y gastric bypass at least a year ago and are experiencing low blood sugar episodes after the surgery. They must not be pregnant, breastfeeding, or have weight fluctuations greater than 5% in the past two months.

Inclusion Criteria

I can sign and understand the consent form for this study.

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

My BMI is 40 or less and my weight has been stable for the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Includes a 3-week Run-in period

Treatment

Randomized, double-blind, placebo-controlled study treatment period with avexitide or placebo

16 weeks

Participants receive daily subcutaneous injections

Open-label extension (Part A)

Participants receive avexitide in an open-label setting to further evaluate safety and efficacy

8 weeks

Participants continue daily subcutaneous injections

Open-label extension (Part B)

Continuation of open-label treatment with avexitide, with unblinded CGM monitoring

24 weeks

Participants continue daily subcutaneous injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Avexitide

Trial Overview The study tests Avexitide against a placebo in managing low blood sugar in post-bariatric patients. It includes initial screening, a controlled treatment period of 16 weeks, and an extension phase where everyone gets Avexitide for about 32 weeks.

How Is the Trial Designed?

Group I: AVEXITIDE Experimental Treatment 1 Intervention

Avexitide (90 mg via subcutaneous \[SC\] injection) will be taken once per day, in the morning at least 60 minutes before the morning meal, through the duration of the treatment and OLE periods.

Group II: PLACEBO Placebo Group 1 Intervention

Placebo will be taken once per day, via subcutaneous \[SC\] injection, in the morning at least 60 minutes before the morning meal, through the duration of the treatment period. Participants receiving Placebo in the double-blind treatment period will transition to Avexitide 90 mg (via subcutaneous \[SC\] injection) in the open-label extension (OLE) period.

Who Is Running the Clinical Trial?

Amylyx Pharmaceuticals Inc.

Lead Sponsor

Trials

12

Recruited

1,600+

Published Research Related to This Trial

In a phase 2 study involving 19 women with post-bariatric hypoglycaemia, subcutaneous avexitide significantly reduced symptoms of hypoglycaemia and improved glucose levels, with both formulations (lyophilized and liquid) showing effectiveness without requiring glycaemic rescue in higher doses.

The liquid formulation of avexitide at 30 mg twice daily resulted in greater and more sustained plasma concentrations compared to the lyophilized version, leading to a 47% increase in glucose nadir and a 67% reduction in peak insulin, indicating its potential as a viable treatment for post-bariatric hypoglycaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. Tan, M., Lamendola, C., Luong, R., et al.[2021]

Exenatide, a GLP-1 mimetic, improves glycemic control in type 2 diabetes through multiple mechanisms, including stimulating insulin secretion and reducing appetite, while significantly lowering HbA1c levels and body weight.

The risk of hypoglycemia is minimized with exenatide since it only stimulates insulin release when blood glucose levels are elevated, making it a safer option for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide. Barnett, AH.[2018]

A single 50-mg dose of albiglutide was well tolerated in 44 subjects with type 2 diabetes and did not impair the body's natural counter-regulatory responses to hypoglycemia, indicating its safety during low blood sugar events.

Albiglutide increased pancreatic β-cell secretion of C-peptide in a glucose-dependent manner when blood sugar levels were above 5.0 mmol/l, suggesting it enhances insulin secretion without increasing the risk of hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus. Hompesch, M., Jones-Leone, A., Carr, MC., et al.[2018]

Dasiglucagon is an effective treatment for severe hypoglycemia, showing significantly faster plasma glucose recovery compared to placebo in clinical trials involving both children and adults.

It is the first glucagon analogue that is stable in aqueous solution, eliminating the need for reconstitution before use, which enhances its practicality for emergency treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasiglucagon: A Novel Ready-to-Use Treatment for Severe Hypoglycemia. Goodhart, AL.[2023]

Effective glycemic control is crucial for preventing complications in type 1 diabetes, but it increases the risk of severe hypoglycemia, which can significantly impact patients' quality of life.

There is a pressing need for better glucagon treatments, particularly stable liquid formulations, to simplify emergency treatment for hypoglycemia and potentially expand its use in other conditions like congenital hyperinsulinism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stable Liquid Glucagon: Beyond Emergency Hypoglycemia Rescue. Wilson, LM., Castle, JR.[2023]

In a case series of 6 patients with sulfonylurea-induced hypoglycemia, octreotide was successfully used to manage prolonged hypoglycemia, especially in patients with renal or heart failure where traditional treatments were ineffective.

Octreotide administration (50 microg subcutaneously every 8 hours) led to a prompt and sustained resolution of hypoglycemia, confirming its efficacy in this context, as evidenced by insulin and C-peptide measurements in 3 of the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of sulfonylurea-induced prolonged hypoglycemia with use of octreotide. Fleseriu, M., Skugor, M., Chinnappa, P., et al.[2021]

Octreotide has been shown to effectively reduce the frequency of sulfonylurea-induced hypoglycemic episodes, as demonstrated in both animal models and human case reports.

In clinical trials, octreotide combined with supplemental dextrose not only increased blood glucose levels but also resulted in fewer hypoglycemic events, supporting its use as a treatment for sulfonylurea overdose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Octreotide's role in the management of sulfonylurea-induced hypoglycemia. Dougherty, PP., Klein-Schwartz, W.[2021]

In a study involving 10 patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), treatment with exenatide did not improve awareness of hypoglycemia compared to placebo, despite a decrease in body weight.

Exenatide treatment did not significantly change glucose levels or the frequency of hypoglycemic events, indicating that while it may aid in weight loss, it does not enhance hypoglycemia awareness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Randomized Controlled Trial. van Meijel, LA., Rooijackers, HM., Tack, CJ., et al.[2023]

Pasireotide, a multireceptor-targeted somatostatin analogue, effectively prevented glyburide-induced hypoglycemia in rats for up to 6 hours in a dose-dependent manner, showing stronger effects in non-fasted conditions.

In contrast, octreotide did not prevent hypoglycemia in fasted and non-fasted rats at lower doses, indicating that pasireotide may be a more potent option for managing severe hypoglycemia caused by sulfonylurea treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) prevents sulfonylurea-induced hypoglycemia in rats. Schmid, HA.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12544540/

SUN-627 Reduction in Rate of Hypoglycemic Events with ... Conclusions: Avexitide 30 mg BID and 60 mg QD led to a 40% and 55% reduction in the composite rate of Level 2&3 events, respectively. The impact ...

2. amylyx.com amylyx.com/news/amylyx-pharmaceuticals-presents-new-exploratory-analyses-from-phase-2-and-phase-2b-clinical-trials-of-avexitide-in-post-bariatric-hypoglycemia-at-endo-2025

July 13, 2025 In two Phase 2 PBH clinical trials, avexitide demonstrated highly statistically significant reductions in hypoglycemic events. These events can ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06747468

Avexitide for Treatment of Post-Bariatric Hypoglycemia The study will assess avexitide compared to placebo for safety and efficacy, measured by reduction of hypoglycemic events. The study includes a Screening period ...

4. metabolismjournal.com metabolismjournal.com/article/S0026-0495(25)00089-7/fulltext

A Phase 3, Multicenter, Randomized, Double-Blind ... Avexitide demonstrated statistically significant reductions in hypoglycemic events and was well tolerated in phase 2 and 2b clinical trials. Objective: ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33616643/

A Randomized, Placebo-controlled Crossover Trial of ... Avexitide administered for 28 days was well tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8277203/

PREVENT: A Randomized, Placebo-controlled Crossover ... Avexitide administered for 28 days was well tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters.

7. academic.oup.com academic.oup.com/jes/article/6/Supplement_1/A349/6787022

OR03-4 Efficacy and Safety of Avexitide for Treatment of ... OR03-4 Efficacy and Safety of Avexitide for Treatment of Hypoglycemia after Gastrointestinal Surgery; Assessment of Novel Dosing Regimens in an ...

8. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.14048

Safety, efficacy and pharmacokinetics of repeat subcutaneous ... Participants receiving Liq avexitide 30 mg twice daily did not require any glycaemic rescue, and on average achieved a 47% increase in glucose ...