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

NCT05007977 | Terminated Phase 1

• 1 other identifier: ZT01-CL-1003
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Keywords

hypoglycemic clamp; glucagon counterregulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Insulin infused

  During each clamp, up to 12 weeks

• Insulin infusion rate

  During each clamp, up to 12 weeks

• Change in catecholamines between euglycemia and hypoglycemia

  During each clamp, up to 12 weeks

• Change in growth hormone between euglycemia and hypoglycemia

  During each clamp, up to 12 weeks

• Change in cortisol between euglycemia and hypoglycemia

  During each clamp, up to 12 weeks

Other Outcomes (1)

• Symptom score during hypoglycemia

  During each clamp, up to 12 weeks

Study Arms (6)

Treatment order: placebo, low dose, high dose

EXPERIMENTAL

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

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

Treatment order: placebo, high dose, low dose

EXPERIMENTAL

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

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

Treatment order: low dose, placebo, high dose

EXPERIMENTAL

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

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

Treatment order: low dose, high dose, placebo

EXPERIMENTAL

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

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

Treatment order: high dose, placebo, low dose

EXPERIMENTAL

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

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

Treatment order: high dose, low dose, placebo

EXPERIMENTAL

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

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

Interventions

ZT-01 low dose DRUG

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

Treatment order: high dose, low dose, placebo; Treatment order: high dose, placebo, low dose; Treatment order: low dose, high dose, placebo; Treatment order: low dose, placebo, high dose; Treatment order: placebo, high dose, low dose; Treatment order: placebo, low dose, high dose

ZT-01 high dose DRUG

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

Treatment order: high dose, low dose, placebo; Treatment order: high dose, placebo, low dose; Treatment order: low dose, high dose, placebo; Treatment order: low dose, placebo, high dose; Treatment order: placebo, high dose, low dose; Treatment order: placebo, low dose, high dose

Placebo DRUG

Single SC injection of placebo during hypoglycemic clamp

Treatment order: high dose, low dose, placebo; Treatment order: high dose, placebo, low dose; Treatment order: low dose, high dose, placebo; Treatment order: low dose, placebo, high dose; Treatment order: placebo, high dose, low dose; Treatment order: placebo, low dose, high dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Zucara Therapeutics Inc.: lead

Study Sites (1)

LMC Manna Research

Toronto, Ontario, M4G 3E8, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Richard Liggins, PhD

  Zucara Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The participant, the investigator and site staff conducting all study procedures are masked to treatment administered at each clamp.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized to the order in which they receive three treatments during consecutive clamps

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: August 17, 2021
• Study Start: July 8, 2021
• Primary Completion: April 12, 2022
• Study Completion: April 18, 2022
• Last Updated: July 12, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)