Study on Lixisenatide and Counterregulation to Hypoglycemia

Type 2 Diabetes Clinical Trial

Official title:

Effect of Lixisenatide on Glucagon Secretion During Hypoglycemia in Patients With Insulin-treated Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02020629
• Other study ID #: 16
• Secondary ID: 2012-004959-36
• Status: Completed
• Phase: Phase 4
• First received: December 16, 2013
• Last updated: December 12, 2015
• Start date: December 2013
• Est. completion date: August 2015

Study information

• Verified date: December 2015
• Source: Lund University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

In hypoglycemia, there is a counterregulation to restore glucose levels. An important part of this counterregulation is the release of the hormone glucagon. Since the GLP-1 receptor agonist lixisenatide has been shown to be associated with a low risk of hypoglycemia, this study examines whether lixisenatide affects the glucagon response to hypoglycemia.

Description:

The study is a single-center, randomized, placebo-controlled study with a cross-over design and examines the glucagon response during a hyperinsulinemic hypoglycemic phase after a 6-week treatment with lixisenatide (or placebo) as add-on to basal insulin and metformin. The hypothesis of the study is that the glucagon counterregulation to hypoglycemia in patients treated with lixisenatide and basal insulin is not lower than in patients treated with basal insulin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male, non-fertile female or female of childbearing potential using a medically approved birth control method aged >18 years.

2. Adult patients with type 2 diabetes treated with basal insulin (NPH insulin, insulin detemir, insulin glargine or insulin degludec) (stable insulin dose (±10%) during the last three months) with concomitant at >3 months stable dose (>1500 mg daily) of metformin.

3. HbA1c <10% (DCCT standard; < 83 mmol(mol) at visit 1.

Exclusion Criteria:

1. Treatment with antihyperglycemic agents apart from basal insulin and metformin, i.e., bolus insulin or other antihyperglycemic oral agents apart from metformin

2. Type 1 diabetes (including LADA)

3. Pregnant or lactating female. Women of childbearing potential with no effective contraceptive method. Acceptable contraceptive include contraceptive sponge; hormonal contraception pills, patches, vaginal rings, injectable contraceptives; and intrauterine devices. Women of childbearing potential (pre-menopausal, not surgically sterile women for at least 3 months prior to the time of screening) must have a confirmed negative serum pregnancy test at screening visit. They must use an effective contraceptive method throughout the study, and agree to repeat pregnancy tests at designated visits. The applied methods of contraception have to meet the criteria for a highly effective method of birth control according to the "Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95)"

4. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly.

5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1

6. Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes or hypoglycemia unawareness

7. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.

8. Treatment with growth hormone and oral or parenteral corticosteroid (> 7 consecutive days of treatment) within 8 weeks prior to visit 1 and thereafter during the whole study period.

9. Use of other investigational drugs within 30 days prior to visit 1.

10. Laboratory findings at the time of screening, including amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN) and P-calcitonin =20 pg/ml (5.9 pmol/L).

11. Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes).

12. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery

13. Allergic reaction to any GLP-1 receptor agonist or to metacresol

14. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting,

15. Cardiovascular, hepatic, neurological, or endocrine disease, active malignant tumor or other major systemic disease or patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult.

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Hypoglycemia
• Type 2 Diabetes

Intervention

Drug:
• Lixisenatide
Lixisenatide is given for 6 weeks whereafter a hypoglycemia clamp is undertaken

Locations

Country	Name	City	State
Sweden	Clinical Research Department	Malmö

Sponsors (1)

Lead Sponsor	Collaborator
Lund University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HbA1c	Change in HbA1c during six weeks treatment	6 weeks	No
Primary	Glucagon response to hypoglycemia	Hypoglycemia is induced by clamp during 30 min; glucagon levels are measured during this time frame	30 min	No
Secondary	Cortisol response to hypoglycemia	Hypoglycemia is induced by a clamp during 30 min. Cortisol is measured during this time frame.	30 min	No
Secondary	Catecholamines	Hypoglycemia is induced by a clamp during 30 min. Catecholamines are measured during this time frame.	30 min	No