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

NCT ID: NCT05007977

Last Updated: 2023-07-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-08
• Study Completion Date: 2022-04-18

Brief 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.

Conditions

Type 1 Diabetes; Hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment order: placebo, low dose, high dose

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

Group Type: EXPERIMENTAL

ZT-01 low dose

Intervention Type: DRUG

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

ZT-01 high dose

Intervention Type: DRUG

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Placebo

Intervention Type: DRUG

Single SC injection of placebo during hypoglycemic clamp

Treatment order: placebo, high dose, low dose

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

Group Type: EXPERIMENTAL

ZT-01 low dose

Intervention Type: DRUG

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

ZT-01 high dose

Intervention Type: DRUG

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Placebo

Intervention Type: DRUG

Single SC injection of placebo during hypoglycemic clamp

Treatment order: low dose, placebo, high dose

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

Group Type: EXPERIMENTAL

ZT-01 low dose

Intervention Type: DRUG

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

ZT-01 high dose

Intervention Type: DRUG

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Placebo

Intervention Type: DRUG

Single SC injection of placebo during hypoglycemic clamp

Treatment order: low dose, high dose, placebo

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

Group Type: EXPERIMENTAL

ZT-01 low dose

Intervention Type: DRUG

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

ZT-01 high dose

Intervention Type: DRUG

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Placebo

Intervention Type: DRUG

Single SC injection of placebo during hypoglycemic clamp

Treatment order: high dose, placebo, low dose

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

Group Type: EXPERIMENTAL

ZT-01 low dose

Intervention Type: DRUG

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

ZT-01 high dose

Intervention Type: DRUG

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Placebo

Intervention Type: DRUG

Single SC injection of placebo during hypoglycemic clamp

Treatment order: high dose, low dose, placebo

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

Group Type: EXPERIMENTAL

ZT-01 low dose

Intervention Type: DRUG

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

ZT-01 high dose

Intervention Type: DRUG

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Placebo

Intervention Type: DRUG

Single SC injection of placebo during hypoglycemic clamp

Interventions

ZT-01 low dose

Single subcutaneous (SC) injection of ZT-01 3 mg during hypoglycemic clamp

Intervention Type: DRUG

ZT-01 high dose

Single SC injection of ZT-01 20 mg during hypoglycemic clamp

Intervention Type: DRUG

Placebo

Single SC injection of placebo during hypoglycemic clamp

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zucara Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Liggins, PhD

Role: STUDY_DIRECTOR

Zucara Therapeutics Inc.

Locations

LMC Manna Research

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

ZT01-CL-1003

Identifier Type: -

Identifier Source: org_study_id