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

Zucara Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Hypoglycemia; Type 1 Diabetes

Treatments: Drug: Placebo; Drug: ZT-01 low dose; Drug: ZT-01 high dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT05007977

ZT01-CL-1003

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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24 participants in 6 patient groups

Treatment order: placebo, low dose, high dose

Experimental group

Description:

Subjects will receive a single administration of each treatment in this order during three consecutive clamps

Treatment:

Drug: ZT-01 high dose

Drug: ZT-01 low dose

Drug: Placebo

Treatment order: placebo, high dose, low dose

Experimental group

Description:

Subjects will receive a single administration of each treatment in this order during three consecutive clamps

Treatment:

Drug: ZT-01 high dose

Drug: ZT-01 low dose

Drug: Placebo

Treatment order: low dose, placebo, high dose

Experimental group

Description:

Subjects will receive a single administration of each treatment in this order during three consecutive clamps

Treatment:

Drug: ZT-01 high dose

Drug: ZT-01 low dose

Drug: Placebo

Treatment order: low dose, high dose, placebo

Experimental group

Description:

Subjects will receive a single administration of each treatment in this order during three consecutive clamps

Treatment:

Drug: ZT-01 high dose

Drug: ZT-01 low dose

Drug: Placebo

Treatment order: high dose, placebo, low dose

Experimental group

Description:

Subjects will receive a single administration of each treatment in this order during three consecutive clamps

Treatment:

Drug: ZT-01 high dose

Drug: ZT-01 low dose

Drug: Placebo

Treatment order: high dose, low dose, placebo

Experimental group

Description:

Subjects will receive a single administration of each treatment in this order during three consecutive clamps

Treatment:

Drug: ZT-01 high dose

Drug: ZT-01 low dose

Drug: Placebo