Overseen ByChristopher D Verrico, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Christopher Verrico
Must not be taking: Opioids, Oxycodone, others
Disqualifiers: Diabetes, Severe cardiovascular, Severe gastrointestinal, others
Approved in 5 jurisdictions
Trial Summary
What is the purpose of this trial?This study will determine the safety and tolerability of exenatide (Bydureon®) as a pharmacotherapy for cocaine use disorder. An inpatient human laboratory study will be conducted in which the self-administration of cocaine, as well as the subjective and physiological effects of cocaine, are evaluated during maintenance on placebo and exenatide.
Although exenatide (Bydureon) is approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, it has not been approved by the FDA to treat cocaine use; therefore, it is called an investigational drug.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but it excludes those whose medications might interact with cocaine or exenatide, or otherwise compromise safety. It's best to discuss your current medications with the study team to see if they might be an issue.
What data supports the effectiveness of the drug Exenatide for treating cocaine use disorder?
Exenatide, a drug used for type 2 diabetes, has shown promise in reducing cocaine use in preclinical studies with animals. In a small human study, it was well-tolerated and showed encouraging results, suggesting it may help reduce cocaine use, but more research is needed.
12345Is exenatide safe for human use?
Exenatide has been used safely in humans for type 2 diabetes, with common side effects including nausea and antibody formation. Some people may experience allergic reactions, but these are rare. In a small study for cocaine use disorder, it was well tolerated without severe adverse events.
13467How is the drug exenatide unique for treating cocaine use disorder?
Exenatide is unique for treating cocaine use disorder because it is a GLP-1 receptor agonist, originally used for type 2 diabetes, and is administered as a once-weekly injection, which may help with medication adherence. Unlike other treatments, it has shown promise in reducing cocaine use in preclinical studies, although it has not yet been proven effective in humans.
12478Eligibility Criteria
This trial is for individuals with Cocaine Use Disorder. Participants must meet certain health requirements, but specific inclusion criteria are not listed. People who have conditions that could interfere with the study or pose a risk to their safety based on other medications or health issues may be excluded.Inclusion Criteria
English-speaking
Resting pulse between 50 and 95 bpm, blood pressure (BP) between 90-150 mmHg systolic and 45-95 mmHg diastolic
Hematology and chemistry laboratory tests within reference limits (±10%), except for pancreatic tests (lipase and amylase) which must be within normal limits
+9 more
Exclusion Criteria
Any laboratory test deemed clinically significant by the study physician
Substance-use disorders other than for CUD that would compromise participant well-being
Participation in a clinical trial within 30 days of admission
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive once-weekly subcutaneous injections of exenatide or placebo for 6 weeks
6 weeks
6 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing Exenatide (Bydureon), which is normally used for type 2 diabetes, to see if it can help people with Cocaine Use Disorder by reducing cocaine's effects and desire for use. It compares Exenatide against a placebo in an inpatient setting where participants' reactions to cocaine are monitored.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Drug: Exenatide 2 mg [Bydureon]Experimental Treatment1 Intervention
Participants will receive once-weekly subcutaneous exenatide (2 mg) injections for 6 weeks.
Group II: Drug: PlaceboPlacebo Group1 Intervention
Participants will receive once-weekly subcutaneous saline (i.e., placebo) injections for 6 weeks.
Exenatide is already approved in United States, United States, United States, European Union, European Union for the following indications:
🇺🇸 Approved in United States as Byetta for:
- Type 2 diabetes mellitus
🇺🇸 Approved in United States as Bydureon for:
- Type 2 diabetes mellitus
🇺🇸 Approved in United States as Bydureon BCise for:
- Type 2 diabetes mellitus
🇪🇺 Approved in European Union as Byetta for:
- Type 2 diabetes mellitus
🇪🇺 Approved in European Union as Bydureon for:
- Type 2 diabetes mellitus
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Michael E. DeBakey VA Medical CenterHouston, TX
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Who Is Running the Clinical Trial?
Christopher VerricoLead Sponsor
Christopher D. VerricoLead Sponsor
References
Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study. [2023]Cocaine use remains a serious public health problem associated with a marked increase in overdose deaths in the past decade. No medications have yet been proven to be effective for the treatment of cocaine use disorder (CUD). Among the highly promising medications have been glucagon-like peptide 1 receptor agonists (GLP-1RA) that are currently used for the treatment of type 2 diabetes mellitus and weight management. Preclinically, GLP-1RAs have been shown to attenuate cocaine self-administration, however, this has not yet been demonstrated in a human laboratory study. The GLP-1RA extended-release exenatide is given as a once-weekly injection, which may be clinically advantageous for addressing medication nonadherence among individuals with CUD. Here, we assess feasibility and safety by reporting on 3 cases of patients with CUD who received 6 weeks of exenatide 2 mg subcutaneously once-weekly in an open-label fashion, along with standard individual drug counseling. We observed excellent attendance and compliance, along with positive end-of-study satisfaction ratings. The medication was well tolerated and without unexpected or severe adverse events. Results for cocaine use and related clinical effects were more mixed, yet encouraging. Future empirical testing of exenatide for treating CUD should utilize a randomized controlled trial design and longer treatment duration.
Testing the effects of the GLP-1 receptor agonist exenatide on cocaine self-administration and subjective responses in humans with cocaine use disorder. [2022]Preclinical rodent studies have demonstrated reduced cocaine taking after administration of glucagon-like peptide 1 (GLP-1) analogues. We investigated effects of a GLP-1 analogue (exenatide) on behavioral and subjective effects of cocaine in individuals with cocaine use disorder (CUD).
[Medication of the month... Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents]. [2018]Exenatide (Byetta) is a synthetic derivative of exendin-4 and an agonist of receptors of glucagon-like peptide-1 (GLP-1). It is resistant to the rapid inactivation by dipeptidylpeptidase-4 and acts as an incretin mimetic. It stimulates insulin secretion by the B cell in a glucose-dependent manner whereas it inhibits glucagon secretion. Exenatide improves mainly postprandial glucose concentrations and lowers glycated haemoglobin (HbA(1c)) levels, without being directly responsible for hypoglycaemia or requiring mandatory home blood glucose monitoring. Furthermore, it slows down gastric emptying and promotes sustained body weight reduction, even in absence of frequently reported nausea following treatment initiation. Exenatide is recommended and reimbursed in Belgium for the treatment of type 2 diabetes, in combination with metformin and a sulfonylurea, in patients not adequately controlled with maximal tolerated doses of these oral glucose-lowering agents. Exenatide is presented as pre-filled pens for subcutaneous injection. The recommended initial dose is 5 microg before morning and evening meals, to be up titrated to 10 microg twice daily. Exenatide may represent a valuable alternative to insulin therapy, especially in overweight or obese patients with type 2 diabetes and not ready to perform home blood glucose monitoring.
[Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR)]. [2022]Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes. The microsphere technology permits a prolonged absorption of exenatide from the subcutaneous depot, which allows one injection per week instead of two injections per day with the initial formulation of exenatide (Byetta). The clinical development programme DURATION showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin (HbA(1c)), with a similar weight loss but a better digestive tolerance profile (less nausea and vomiting after treatment initiation), compared with the twice daily 10 microg exenatide. When compared to other glucose-lowering agents, once weekly exenatide is more efficacious than sitagliptin, pioglitazone or basal insulin (glargine or detemir), with the advantage of producing weight loss and lowering arterial blood pressure. It does not induce hypoglycaemia and does not necessarily require home blood glucose monitoring, two advantages compared with insulin therapy. Bydureon is currently only reimbursed in Belgium after failure of and in addition to metformin-sulfonylurea combination.
Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. [2018]Exenatide extended-release (exenatide ER) [Bydureon(®)] is a glucagon-like peptide-1 receptor agonist, approved for the treatment of type 2 diabetes mellitus. It is injected subcutaneously by patients once weekly, with no dose titration required. This article updates an earlier review of exenatide ER in the management of type 2 diabetes, focusing on recently published data. In randomized, controlled trials, adjunctive exenatide ER 2 mg once weekly for 24-30 weeks significantly improved glycaemic control and reduced bodyweight in patients with inadequately controlled type 2 diabetes despite diet plus exercise and/or oral antihyperglycaemic drugs (OADs). These beneficial effects of exenatide ER were maintained after up to 6 years of treatment. In patients receiving one or more OADs, addition of exenatide ER provided better glycaemic control than an immediate-release formulation of exenatide (exenatide twice daily), sitagliptin, pioglitazone, insulin glargine or insulin detemir, and was slightly less effective than liraglutide. In patients treated with diet plus exercise alone, adjunctive exenatide ER was noninferior to metformin and superior to sitagliptin, but was not noninferior to pioglitazone. Exenatide ER was generally well tolerated, with a low inherent risk of hypoglycaemia. The most common adverse events were mild to moderate gastrointestinal events, injection-site reactions and headache. Thus, exenatide ER is a useful treatment option in the management of type 2 diabetes. It offers a convenient, once-weekly regimen and can be administered by patients via a pen injection system or syringes and needles.
Benefit-risk assessment of exenatide in the therapy of type 2 diabetes mellitus. [2022]Exenatide is the first incretin mimetic, introduced into type 2 diabetes mellitus therapy in 2005, with first approval in the US. It is a glucagon-like peptide-1 (GLP-1) receptor agonist that can be used for treatment by twice-daily injection. A long-acting release formulation for once-weekly injection is in clinical development. Clinical studies and postmarketing experience with exenatide have shown a significant and sustained reduction in glycosylated haemoglobin (HbA(1c)) by approximately 1% together with other gylcaemic parameters without an intrinsic risk for hypoglycaemias, and a reduction in bodyweight by 5.3 kg in 82 weeks. Blood pressure and lipids are also favourably affected, but hard cardiovascular endpoints are not yet available. Animal studies show an improvement of beta-cell function and an increase in beta-cell mass after exenatide treatment. The most frequent adverse events associated with exenatide therapy are nausea and antibody formation (both approximately 40%). Nausea, mostly mild and transient, was responsible for a 6% dropout rate in clinical studies. A recent review on the association of acute pancreatitis with exenatide treatment showed no increased risk (relative risk 1.0; 95% CI 0.6, 1.7). This review gives a benefit-risk assessment of exenatide.
Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide. [2021]Objective: To report a case of systemic hypersensitivity to the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide used in diabetes care to provide significant information within the context of postmarketing safety surveillance of this new drug class. Case Summary: We report on a 52-year-old male with insufficiently controlled diabetes. GLP-1 agonist treatment was indicated and the patient was started on 5 to 10 µg exenatide (Byetta) twice daily, which had to be stopped after 1 month due to intolerable nausea. One year later, an attempt with 0.6 to 1.8 mg liraglutide (Victoza) once daily was well tolerated but lacked efficacy after a few months. Finally, the patient was started on 2 mg exenatide (Bydureon) once weekly. Concomitant treatment included metformine 1000 mg twice daily and candesartan/hydrochlorothiazide (Blopress Plus) 16/12.5 mg once daily. A few hours after the second injection, local urticaria and disseminated pruritus evolved and after the third injection pruritus, urticaria, and shortness of breath developed, which resolved to antihistamines and corticosteroids. Intradermal tests were positive for Byetta (1:1000) and Bydureon (1:100) (both exenatide), while Victoza (liraglutide) was negative (1:10). Specific immunoglobulin E (IgE) to the drugs was not available for testing. Discussion: An objective causality assessment revealed that the adverse effect to exenatide (Bydureon) was probable (Naranjo probability scale: score of 8). Consistency was established through positive skin tests and the biological explanation that the administration of GLP-1 receptor agonists has been associated with antibody formation. Conclusion: Considering emerging use of GLP-1 receptor agonists, systemic hypersensitivity should be recognized as a risk in clinical practice.
Long-acting preparations of exenatide. [2021]Exenatide has been widely used for the treatment of type 2 diabetes mellitus. However, its short plasma half-life of 2.4 hours has limited its clinical application. The exenatide products on the market, twice-daily Byetta™ and once-weekly Bydureon™ (both Amylin Pharmaceuticals, San Diego, CA, USA), are still not perfect. Many researchers have attempted to prolong the acting time of exenatide by preparing sustained-release dosage forms, modifying its structure, gene therapies, and other means. This review summarizes recent advances in long-acting exenatide preparations.