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

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

Overview

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).

Interventions

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

Primary outcome measures

• Incidence of nocturnal hypoglycemia [Time frame: During each 28 day treatment period]

Secondary outcome measures (3)

• Incidence and severity of adverse events (AEs) [Time frame: During each 28 day treatment period and 2-week followup]
• Glucose time below range [Time frame: During each 28 day treatment period]
• Incidence of hypoglycemia [Time frame: During each 28 day treatment period]

Eligibility criteria

Inclusion criteria

• Has type 1 diabetes for at least 5 years
• is at risk of nocturnal hypoglycemia (if using personal CGM, time below 54 mg/dL at least 1% over previous 4 weeks at screening; if not using personal CGM then recent history suggestive of nocturnal hypoglycemia at screening and time below 54 mg/dL at least 1% 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

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 38 centers

• Kirklin Clinic of UAB Hospital-Endocrinology/Diabetes Clinic — Birmingham
• Medical Investigations Indications Inc. — Little Rock
• Headlands Research — Escondido
• USC Keck Medicine Eastside Center for Diabetes — Los Angeles
• LCGK Research — San Carlos
• Barbara Davis Center for Diabetes — Aurora
• Yale University - Diabetes Research Office — New Haven
• East Coast Institute for Research LLC — Jacksonville
• … and 30 more centers

Canada · 8 centers

• Centricity Research Calgary Endocrinology — Calgary
• Richmond Road Diagnostic & Treatment Centre, Clinical Trials Unit — Calgary
• BC Diabetes — Vancouver
• Centricity Research Barrie Endocrinology — Barrie
• Centricity Research Vaughan Endocrinology — Concord
• Centricity Research Etobicoke Endocrinology — Etobicoke
• Centricity Research Toronto — Toronto
• Mount Sinai Hospital: Leadership Sinai Centre for Diabetes — Toronto

Identifiers

NCT: NCT05762107 · ZT01-CL-2001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗