A Study of the Effect of ZT-01 on Night-time Hypoglycemia in Type 1 Diabetes

Type 1 Diabetes Mellitus With Hypoglycemia Clinical Trial

— ZONE  

Official title:

A Phase 2a Randomized, Double-blind, Placebo-controlled, Multiple-dose, Crossover Study of the Effect of ZT-01 on Frequency of Nocturnal Hypoglycemia in Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05762107
• Other study ID #: ZT01-CL-2001
• Status: Recruiting
• Phase: Phase 2
• Start date: July 28, 2023
• Est. completion date: July 2025

Study information

• Verified date: April 2024
• Source: Zucara Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to learn about the effect of the study drug (ZT-01) on low blood sugar (hypoglycemia) in adults with type 1 diabetes (T1D) who have been having low blood sugars ("hypos") at night. ZT-01 increases the amount of a hormone called glucagon during low blood sugar, and this may help prevent the occurrence of hypos. The main questions this trial aims to answer are whether ZT-01 lowers the number of hypos happening at night, and what its effects are on blood sugar levels. The safety of ZT-01 will also be measured.

Participants will be asked to wear a study-provided continuous glucose monitor (CGM) during two 4-week periods when they will self-inject the study drug before bed. They will get ZT-01 at one of three dose levels during one period, and placebo (which looks like the study drug but doesn't contain the active ingredient) during the other. Neither the participant nor the study site will know what they are receiving during each treatment period or see data from the CGM. The participant will continue to use their usual methods of measuring blood sugar (including their personal CGM) and giving insulin during the study. The participant will be asked to complete a short diary each evening, and will be asked to upload the CGM data to a study phone every day.

If a participant uses their own CGM and is willing to share information on how often they have low blood sugar with the study site at the first visit to see if they meet study entry requirements, they will have 6 study visits, 2 study phone calls, and be in the study for about 16 weeks. If they don't use CGM or don't want to share their information, then they will be asked to wear a study CGM for an extra 4 weeks to find out how many low blood sugars they have, and will have an extra visit.

Study participants will be asked to give blood and urine for testing to see whether they meet the requirements to enter the study, and at the start and end of each treatment period to see if the study treatment has any effects. They will also have their blood pressure and temperature taken at each study visit, and have an ECG at 4 visits to measure the electrical activity of their heart.

Some participants will be asked to also take part in a sub-study where their blood level of ZT-01 and glucagon is measured, after the first and last dose. They will be asked to stay at the study site overnight for each set of measurements (4 in total).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: July 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Has type 1 diabetes for at least 5 years

• Has history of recent nocturnal hypoglycemia (if using personal CGM, 4 events <54 mg/dL over previous 4 weeks at screening; if not using personal CGM then recent history of nocturnal symptomatic hypoglycemia at screening and 4 events over 4 weeks using blinded study CGM during additional screening)

• HbA1c at screening </= 10.0%

• Body mass index (BMI) at screening >/=18.5 to <33 kg/m2

Exclusion Criteria:

• Currently uses automated insulin delivery system, eg closed loop or artificial pancreas

• Has been hospitalized for diabetic ketoacidosis (DKA) more than once within previous 6 months

• Has experienced >/= 1 severe hypoglycemia (requiring assistance) during previous 4 weeks or >2 in previous 3 months

• Diagnosis of type 2 diabetes, pheochromocytoma, insulinoma, glucagonoma, acromegaly, Cushing's disease, glycogen storage disease, adrenal insufficiency

• Clinically significant kidney disease

• Abnormal liver function

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
Subject receives Placebo by subcutaneous injection daily for 28 days
• ZT-01, 7 mg
Subject receives ZT-01 7 mg by subcutaneous injection daily for 28 days
• ZT-01, 15 mg
Subject receives ZT-01 15 mg by subcutaneous injection daily for 28 days
• ZT-01, 22 mg
Subject receives ZT-01 22 mg by subcutaneous injection daily for 28 days

Locations

Country	Name	City	State
Canada	Centricity Research Barrie Endocrinology	Barrie	Ontario
Canada	Centricity Research Calgary Endocrinology	Calgary	Alberta
Canada	Centricity Research Vaughan Endocrinology	Concord	Ontario
Canada	Centricity Research Etobicoke Endocrinology	Etobicoke	Ontario
Canada	Centricity Research Toronto	Toronto	Ontario
Canada	BC Diabetes	Vancouver	British Columbia
United States	Texas Diabetes & Endocrinology, PA	Austin	Texas
United States	East Coast Institute for Research LLC	Jacksonville	Florida
United States	Palm Research Center, Inc.	Las Vegas	Nevada
United States	USC Keck Medicine Eastside Center for Diabetes	Los Angeles	California
United States	East Coast Institute for Research	Macon	Georgia
United States	Lucas Research Inc.	Morehead City	North Carolina
United States	Diabetes & Glandular Disease Clinic	San Antonio	Texas
United States	Endeavor Clinical Trials LLC	San Antonio	Texas
United States	Metabolic Research Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Zucara Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glucose time in range	Glucose time in range (70-180 mg/dL, %) compared to placebo	During each 28-day treatment period
Other	Mean glycemic variability	Percent coefficient of variation of glucose values compared to placebo	During each 28 day treatment period
Other	Mean glucose concentration	Mean glucose concentration compared to placebo	During each 28 day treatment period
Primary	Incidence of nocturnal hypoglycemia	Rate of nocturnal (midnight to 06:00 AM) hypoglycemic events (glucose <54 mg/dL) lasting at least 15 minutes, compared to placebo	During each 28 day treatment period
Secondary	Incidence and severity of adverse events (AEs)	Number of patients experiencing AEs compared to placebo	During each 28 day treatment period and 2-week followup
Secondary	Glucose time below range	Glucose time below 54 mg/dL (as %) compared to placebo	During each 28 day treatment period
Secondary	Incidence of hypoglycemia	Number of hypoglycemic events (glucose <70 mg/dL for at least 15 minutes, compared to placebo	During each 28 day treatment period