Clinical trial NCT05762107: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus With Hypoglycemia
Keywords: nocturnal hypoglycemia
Lead sponsor: Zucara Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-09
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The participant will be randomized to receive placebo and one of three dose levels of ZT-01 in a crossover design
Primary purpose: PREVENTION

Brief 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).


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

Primary outcomes:
measure: Incidence of nocturnal hypoglycemia
timeFrame: During each 28 day treatment period
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs)
timeFrame: During each 28 day treatment period and 2-week followup
measure: Glucose time below range
timeFrame: During each 28 day treatment period
measure: Incidence of hypoglycemia
timeFrame: During each 28 day treatment period
Other outcomes:
measure: Glucose time in range
timeFrame: During each 28-day treatment period
measure: Mean glycemic variability
timeFrame: During each 28 day treatment period
measure: Mean glucose concentration
timeFrame: During each 28 day treatment period
Locations:
city: Escondido
country: United States
facility: Headlands Research
state: California
city: Los Angeles
country: United States
facility: USC Keck Medicine Eastside Center for Diabetes
state: California
city: San Carlos
country: United States
facility: LCGK Research
state: California
city: Jacksonville
country: United States
facility: East Coast Institute for Research LLC
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Port Charlotte
country: United States
facility: Hanson Diabetes Center
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute
state: Florida
city: Macon
country: United States
facility: East Coast Institute for Research
state: Georgia
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: MedStar Good Samaritan Hospital
state: Maryland
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Morehead City
country: United States
facility: Lucas Research Inc.
state: North Carolina
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology, PA
state: Texas
city: Mesquite
country: United States
facility: Southern Endocrinology Associates
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic
state: Texas
city: Calgary
country: Canada
facility: Centricity Research Calgary Endocrinology
state: Alberta
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Barrie
country: Canada
facility: Centricity Research Barrie Endocrinology
state: Ontario
city: Concord
country: Canada
facility: Centricity Research Vaughan Endocrinology
state: Ontario
city: Etobicoke
country: Canada
facility: Centricity Research Etobicoke Endocrinology
state: Ontario
city: Toronto
country: Canada
facility: Centricity Research Toronto
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital: Leadership Sinai Centre for Diabetes
state: Ontario
Study officials:
References: