Effect of ZT-01 on Glucagon During Hypoglycemia in Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

Official title:

Pharmacodynamic Evaluation of ZT-01 in a Stepped Hypoglycemic Clamp Model in Subjects With Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05007977
• Other study ID #: ZT01-CL-1003
• Status: Terminated
• Phase: Phase 1
• Start date: July 8, 2021
• Est. completion date: April 18, 2022

Study information

• Verified date: July 2023
• Source: Zucara Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether ZT-01 increases the glucagon response to hypoglycemia in type 1 diabetes (T1D). ZT-01 is a specific somatostatin (SST) type 2 receptor antagonist hypothesized to increase the counterregulatory glucagon release during hypoglycemia, which is impaired in diabetes, and may thus reduce the occurrence of hypoglycemia.

Approximately 25 participants with well-controlled type 1 diabetes will be recruited to a crossover study and be randomized to the order in which they receive a single administration of placebo, low dose and high dose ZT-01 during three euglycemic-hypoglycemic clamps 2 to 6 weeks apart, with a follow-up visit approximately 1 week after the final clamp.

Participants will stay overnight in the clinic before each clamp, and their plasma glucose (PG) will be kept at euglycemic levels with IV insulin and dextrose as needed. The following morning, the clamp will begin and the subject's PG will be kept at 5.5 mmol/L (euglycemia) with variable IV insulin (and dextrose as needed). Study treatment will be administered during this euglycemic period, and then insulin will be increased so that PG falls to a plateau of mild hypoglycemia, and then increased further to clinically significant hypoglycemia. Release of glucagon and other counterregulatory hormones will be measured, and a symptom score will be completed, during euglycemia before and following study treatment, and during each level of hypoglycemia. Following the clamp, the participant's blood glucose will be returned to normal levels prior to leaving the clinic.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: April 18, 2022
• Est. primary completion date: April 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Type 1 diabetes for at least 5 years and receiving insulin as the only T1D therapy

• HbA1c =6.0 and =9.0 %

• BMI =18 to =27 kg/m^2

• Normal thyroid function

Exclusion Criteria:

• Impaired hypoglycemia awareness

• Severe hypoglycemia or diabetic ketoacidosis (DKA) within 3 months

• Abnormal blood pressure or ECG, clinically significant cardiovascular, cerebrovascular or peripheral vascular disease

• History of pheochromocytoma, insulinoma, glucagonoma, acromegaly, Cushing's disease, glycogen storage disease or adrenal insufficiency; ongoing or previous treatment with octreotide, lanreotide or pasireotide

• Current use of systemic corticosteroids or beta-blockers

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes

Intervention

Drug:
• ZT-01 low dose
Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp
• ZT-01 high dose
Single SC injection of ZT-01 20 mg during hypoglycemic clamp
• Placebo
Single SC injection of placebo during hypoglycemic clamp

Locations

Country	Name	City	State
Canada	LMC Manna Research	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Zucara Therapeutics Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Symptom score during hypoglycemia	The Edinburgh hypoglycemia symptom score assesses the presence and extent (on a scale of 1, not present to 7, present a great deal) of 16 common symptoms which may be experienced by an individual while their blood glucose is low. The score does not indicate any outcome.	During each clamp, up to 12 weeks
Primary	Change in glucagon between euglycemia and hypoglycemia	Mean and peak glucagon level during euglycemia and each hypoglycemic period of the clamp	During each clamp, up to 12 weeks
Secondary	Insulin infused	Insulin administered during euglycemia and each hypoglycemic period of the clamp	During each clamp, up to 12 weeks
Secondary	Insulin infusion rate	Rate of insulin administered during euglycemia and each hypoglycemic period of the clamp	During each clamp, up to 12 weeks
Secondary	Change in catecholamines between euglycemia and hypoglycemia	Epinephrine and norepinephrine during euglycemia and each stable hypoglycemic period of the clamp	During each clamp, up to 12 weeks
Secondary	Change in growth hormone between euglycemia and hypoglycemia	Growth hormone during euglycemia and each stable hypoglycemic period	During each clamp, up to 12 weeks
Secondary	Change in cortisol between euglycemia and hypoglycemia	Cortisol during euglycemia and each stable hypoglycemic period	During each clamp, up to 12 weeks