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An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism

An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04538989
Enrollment
23
Registered
2020-09-04
Start date
2020-02-24
Completion date
2022-08-19
Last updated
2025-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Hyperinsulinism

Keywords

Hypoglycemia, Congenital Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases, Pancreatic Diseases, Digestive System Diseases, Hyperinsulinism

Brief summary

The objective of this trial is to evaluate the safety, tolerability and glucose-raising effects of RZ358 in patients with Congenital Hyperinsulinism (HI).

Detailed description

There is a significant unmet medical need to develop new therapies aimed at preventing chronic recurrent hypoglycemia in congenital HI, the most common cause of persistent hypoglycemia in children. RZ358 is a human mAb that allosterically attenuates excessive insulin action on target cells. Therefore, RZ358 is ideally suited as a potential therapy for hyperinsulinism, and it is being developed to treat the hypoglycemia associated with diseases such as congenital HI. This is a Phase 2, multicenter, open label clinical study designed to assess the safety and efficacy of four progressively higher doses of RZ358 in separate groups of patients with hyperinsulinemic hypoglycemia due to Congenital HI, not adequately controlled with or without current standard of care. A screening period of up to 5 weeks will evaluate eligibility. Once enrolled, RZ358 will be administered bi-weekly over 8 weeks, and then patients will complete a post-treatment follow-up period of 13 weeks.

Interventions

DRUGRZ358 Sequential Group Cohort 1

IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)

DRUGRZ358 Sequential Group Cohort 2

IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)

DRUGRZ358 Sequential Group Cohort 3

IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)

DRUGRZ358 Sequential Group Cohort 4

IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)

Sponsors

Rezolute
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
2 Years to 45 Years
Healthy volunteers
No

Inclusion criteria

* Male or female age 2-45 years old (except age 12-45 in US) with an established clinical diagnosis of congenital hyperinsulinism * Able to provide written informed consent or, as applicable, assent * Confirmed hypoglycemia as assessed by CGM, SMBG, and clinical evaluation, during Screening * Willingness to use contraception if of child-bearing potential

Exclusion criteria

* Out of range blood work for study entry * Body Mass index outside of study entry criteria * History of malignancy * Clinically significant diseases, seropositivity for HIV, hepatitis B or C antibody * Use of systemic corticosteroids within 30 days before Screening * Known or suspected allergy to the study drug * Recent use of an investigational drug or treatment, or participation in an investigational study * Pregnant or lactating women * History of drug abuse or excessive alcohol use

Design outcomes

Primary

MeasureTime frameDescription
Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)8 weeksThe median of average daily percent time within the glucose target range 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline and End of Treatment (EOT) is reported.
Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)8 weeksThe average daily percent time within the glucose target range (70-180 mg/dL) is compared from baseline to end of treatment (EOT) and the median percent change of that difference is reported.
Repeat Dose Pharmacokinetics of RZ358Pre dose Weeks 1,3,5,7, 1-hr post dose Week 1 and Week 7, and Follow up on Days 14, Day 28, Day 42, and Day 105All patients who received RZ358 and for whom the primary PK data was considered to be sufficient and interpretable were to be included in the PK analyses. Individual and mean plasma concentration data is summarized descriptively at the specified timepoints. The results of this study may be combined with those of other studies for analysis and modeling (e.g., population PK and PK-PD), and therefore the PK parameters are reported separately, as part of an iterative population PK approach.

Secondary

MeasureTime frameDescription
Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)8 weeksThe average daily percent time in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\]), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)8 weeksThe median of average duration (minutes) in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\] ), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia by CGM at baseline (BL) and end of treatment (EOT) is reported.
Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)8 weeksThe average duration (minutes) in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\] ), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia by CGM is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.
Occurrence of Hypoglycemia During Fasting Challenge8 WeeksThe occurrence of hypoglycemia during a 12 Hour fasting challenge.
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)8 weeksThe median of average weekly number of overall hypoglycemia events (\<70 mg/dL \[3.9mmol/L\], moderate hypoglycemia events (\<60 mg/dL \[3.3 mmol/L\] and severe hypoglycemia events (\<50 mg/dL \[2.8mmol/L\]) by SMBG at baseline (BL) and end of treatment (EOT) is reported.
Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)8 weeksThe average hypoglycemia events per day at each of the specified glucose thresholds \[\<70, \<60, and \<50 mg/dL (3.9, 3.3, and 2.8 mmol/L)\], by CGM is compared from baseline (BL) to end of treatment (EOT) and the median net changes of those differences are reported.
Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)8 weeksThe median of average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) at baseline (BL) and end of treatment (EOT) is reported.
Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)8 weeksThe average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) is compared from baseline (BL) to end of treeatment (EOT) and the median percent change of that difference is reported.
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)8 weeksThe median of average hypoglycemia events per day at each of the specified glucose thresholds \[\<70, \<60, and \<50 mg/dL (3.9, 3.3, and 2.8 mmol/L)\], by CGM at baseline (BL) and end of treatment (EOT) is reported.
Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)8 weeksThe average weekly number overall hypoglycemia events (\<70 mg/dL \[3.9mmol/L\], moderate hypoglycemia events (\<60 mg/dL \[3.3 mmol/L\] and severe hypoglycemia events (\<50 mg/dL \[2.8mmol/L\]) by SMBG is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)8 weeksThe median of average daily percent time in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\]), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia at baseline (BL) and end of treatment (EOT) is reported.

Countries

Bulgaria, Canada, Denmark, Georgia, Germany, Israel, Russia, Spain, Turkey (Türkiye), United Kingdom, United States

Participant flow

Recruitment details

Sites were recruited based on cHI professional expertise and sufficient patient panels and advocacy referrals.

Pre-assignment details

NA; open-label study

Participants by arm

ArmCount
RZ358 Cohort 1
RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)
4
RZ358 Cohort 2
RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)
8
RZ358 Cohort 3
RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
8
RZ358 Cohort 4
RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)
3
Total23

Baseline characteristics

CharacteristicRZ358 Cohort 4TotalRZ358 Cohort 1RZ358 Cohort 2RZ358 Cohort 3
Age, Categorical
<=18 years
3 Participants22 Participants4 Participants7 Participants8 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
0 Participants1 Participants0 Participants1 Participants0 Participants
Age, Continuous4.0 years
STANDARD_DEVIATION 2
6.7 years
STANDARD_DEVIATION 5.5
5.8 years
STANDARD_DEVIATION 4.35
9.3 years
STANDARD_DEVIATION 6.88
5.8 years
STANDARD_DEVIATION 5.12
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
3 Participants21 Participants4 Participants6 Participants8 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants2 Participants0 Participants2 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants2 Participants0 Participants2 Participants0 Participants
Race (NIH/OMB)
White
3 Participants20 Participants4 Participants6 Participants7 Participants
Region of Enrollment
Bulgaria
0 participants3 participants3 participants0 participants0 participants
Region of Enrollment
Denmark
0 participants1 participants0 participants1 participants0 participants
Region of Enrollment
Georgia
0 participants1 participants1 participants0 participants0 participants
Region of Enrollment
Germany
0 participants1 participants0 participants0 participants1 participants
Region of Enrollment
Israel
0 participants1 participants0 participants1 participants0 participants
Region of Enrollment
Russia
3 participants5 participants0 participants0 participants2 participants
Region of Enrollment
Spain
0 participants1 participants0 participants1 participants0 participants
Region of Enrollment
Turkey
0 participants7 participants0 participants3 participants4 participants
Region of Enrollment
United Kingdom
0 participants2 participants0 participants1 participants1 participants
Region of Enrollment
United States
0 participants1 participants0 participants1 participants0 participants
Sex: Female, Male
Female
1 Participants13 Participants4 Participants5 Participants3 Participants
Sex: Female, Male
Male
2 Participants10 Participants0 Participants3 Participants5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 40 / 80 / 80 / 3
other
Total, other adverse events
2 / 47 / 85 / 82 / 3
serious
Total, serious adverse events
0 / 42 / 81 / 80 / 3

Outcome results

Primary

Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)

The median of average daily percent time within the glucose target range 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline and End of Treatment (EOT) is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at BL81.7 Daily Percent Time
RZ358 Cohort 1Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at 8 weeks (EOT)84.8 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at 8 weeks (EOT)78.5 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at BL72.9 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at BL83.4 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at 8 weeks (EOT)82.9 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at BL59.3 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at 8 weeks (EOT)70.8 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at 8 weeks (EOT)79.1 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Daily Percent Time in 70-180 mg/dL at BL76.9 Daily Percent Time
Primary

Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)

The average daily percent time within the glucose target range (70-180 mg/dL) is compared from baseline to end of treatment (EOT) and the median percent change of that difference is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureValue (MEDIAN)
RZ358 Cohort 1Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)6.19 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)0.31 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)5.52 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)9.07 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)4.59 Percent Change
Primary

Repeat Dose Pharmacokinetics of RZ358

All patients who received RZ358 and for whom the primary PK data was considered to be sufficient and interpretable were to be included in the PK analyses. Individual and mean plasma concentration data is summarized descriptively at the specified timepoints. The results of this study may be combined with those of other studies for analysis and modeling (e.g., population PK and PK-PD), and therefore the PK parameters are reported separately, as part of an iterative population PK approach.

Time frame: Pre dose Weeks 1,3,5,7, 1-hr post dose Week 1 and Week 7, and Follow up on Days 14, Day 28, Day 42, and Day 105

Population: PK Population; Data from Cohort 1, 2 and 4 was not collected during Pre-dose Week 1.

ArmMeasureGroupValue (MEAN)
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Follow-Up Day 14/EOT59542 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Pre dose Week 731902 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Week 794593 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Follow-up Day 2846751 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Pre dose Week 338951 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Follow-up Day 4223166 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Pre dose Week 520692 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Follow-up Day 1052307 ng/mL
RZ358 Cohort 1Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Wk1/D129093 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Pre dose Week 582646 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Pre dose Week 328397 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Pre dose Week 756919 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Follow-up Day 1054231 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Week 7178090 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Wk1/D1120368 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Follow-up Day 2839385 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Follow-up Day 4224226 ng/mL
RZ358 Cohort 2Repeat Dose Pharmacokinetics of RZ358Follow-Up Day 14/EOT70990 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Follow-up Day 2863201 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Pre dose Week 155648 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Follow-up Day 1059269 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Pre dose Week 341512 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Follow-up Day 4243034 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Pre dose Week 574457 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Pre dose Week 795721 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Week 7280843 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Wk1/D1164047 ng/mL
RZ358 Cohort 3Repeat Dose Pharmacokinetics of RZ358Follow-Up Day 14/EOT105005 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Follow-up Day 4237394 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Pre dose Week 534243 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Pre dose Week 38961 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Follow-up Day 2852039 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Follow-Up Day 14/EOT110134 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Wk1/D143593 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Pre dose Week 755532 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Follow-up Day 1054194 ng/mL
RZ358 Cohort 4Repeat Dose Pharmacokinetics of RZ358Post dose (1hr) Week 7245905 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Follow-up Day 1054857 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Pre dose Week 155648 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Post dose (1hr) Wk1/D189333 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Pre dose Week 328999 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Pre dose Week 564808 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Pre dose Week 767823 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Post dose (1hr) Week 7217295 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Follow-Up Day 14/EOT82683 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Follow-up Day 4231066 ng/mL
RZ358 PooledRepeat Dose Pharmacokinetics of RZ358Follow-up Day 2850125 ng/mL
Secondary

Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)

The average hypoglycemia events per day at each of the specified glucose thresholds \[\<70, \<60, and \<50 mg/dL (3.9, 3.3, and 2.8 mmol/L)\], by CGM is compared from baseline (BL) to end of treatment (EOT) and the median net changes of those differences are reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <70 mg/dL (3.9mmol/L) from BL-0.47 Events Per Day
RZ358 Cohort 1Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) from BL-0.28 Events Per Day
RZ358 Cohort 1Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) from BL-0.32 Events Per Day
RZ358 Cohort 2Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) from BL-0.82 Events Per Day
RZ358 Cohort 2Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <70 mg/dL (3.9mmol/L) from BL-1.41 Events Per Day
RZ358 Cohort 2Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) from BL-0.98 Events Per Day
RZ358 Cohort 3Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) from BL-0.63 Events Per Day
RZ358 Cohort 3Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <70 mg/dL (3.9mmol/L) from BL-1.49 Events Per Day
RZ358 Cohort 3Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) from BL-0.06 Events Per Day
RZ358 Cohort 4Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <70 mg/dL (3.9mmol/L) from BL-1.14 Events Per Day
RZ358 Cohort 4Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) from BL-0.35 Events Per Day
RZ358 Cohort 4Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) from BL-0.39 Events Per Day
RZ358 PooledMedian Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) from BL-0.61 Events Per Day
RZ358 PooledMedian Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <70 mg/dL (3.9mmol/L) from BL-1.05 Events Per Day
RZ358 PooledMedian Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL)Median Net Change of Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) from BL-0.30 Events Per Day
Secondary

Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)

The median of average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) at baseline (BL) and end of treatment (EOT) is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at BL80.8 8-hour Overnight Percent Time
RZ358 Cohort 1Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at 8 Weeks (EOT)84.4 8-hour Overnight Percent Time
RZ358 Cohort 2Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at BL75.0 8-hour Overnight Percent Time
RZ358 Cohort 2Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at 8 Weeks (EOT)81.1 8-hour Overnight Percent Time
RZ358 Cohort 3Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at BL82.1 8-hour Overnight Percent Time
RZ358 Cohort 3Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at 8 Weeks (EOT)89.2 8-hour Overnight Percent Time
RZ358 Cohort 4Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at 8 Weeks (EOT)73.8 8-hour Overnight Percent Time
RZ358 Cohort 4Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at BL48.0 8-hour Overnight Percent Time
RZ358 PooledMedian of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at BL75.0 8-hour Overnight Percent Time
RZ358 PooledMedian of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average 8h Overnight Percent Time in 70-180 mg/dL at 8 Weeks (EOT)80.1 8-hour Overnight Percent Time
Secondary

Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)

The median of average duration (minutes) in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\] ), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia by CGM at baseline (BL) and end of treatment (EOT) is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at BL204 Daily Minutes in Hypoglycemia
RZ358 Cohort 1Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at 8 Weeks (EOT)158 Daily Minutes in Hypoglycemia
RZ358 Cohort 1Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at BL90.5 Daily Minutes in Hypoglycemia
RZ358 Cohort 1Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at 8 Weeks (EOT)65.8 Daily Minutes in Hypoglycemia
RZ358 Cohort 1Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at BL26.1 Daily Minutes in Hypoglycemia
RZ358 Cohort 1Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at 8 Weeks (EOT)15.00 Daily Minutes in Hypoglycemia
RZ358 Cohort 2Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at BL46.3 Daily Minutes in Hypoglycemia
RZ358 Cohort 2Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at 8 Weeks (EOT)14.8 Daily Minutes in Hypoglycemia
RZ358 Cohort 2Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at BL266 Daily Minutes in Hypoglycemia
RZ358 Cohort 2Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at BL113 Daily Minutes in Hypoglycemia
RZ358 Cohort 2Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at 8 Weeks (EOT)35.7 Daily Minutes in Hypoglycemia
RZ358 Cohort 2Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at 8 Weeks (EOT)84.1 Daily Minutes in Hypoglycemia
RZ358 Cohort 3Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at 8 Weeks (EOT)25.3 Daily Minutes in Hypoglycemia
RZ358 Cohort 3Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at BL14.3 Daily Minutes in Hypoglycemia
RZ358 Cohort 3Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at BL180 Daily Minutes in Hypoglycemia
RZ358 Cohort 3Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at BL67.9 Daily Minutes in Hypoglycemia
RZ358 Cohort 3Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at 8 Weeks (EOT)76.7 Daily Minutes in Hypoglycemia
RZ358 Cohort 3Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at 8 Weeks (EOT)8.67 Daily Minutes in Hypoglycemia
RZ358 Cohort 4Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at 8 Weeks (EOT)105 Daily Minutes in Hypoglycemia
RZ358 Cohort 4Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at 8 Weeks (EOT)287 Daily Minutes in Hypoglycemia
RZ358 Cohort 4Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at BL257 Daily Minutes in Hypoglycemia
RZ358 Cohort 4Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at 8 Weeks (EOT)16.7 Daily Minutes in Hypoglycemia
RZ358 Cohort 4Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at BL39.3 Daily Minutes in Hypoglycemia
RZ358 Cohort 4Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at BL472 Daily Minutes in Hypoglycemia
RZ358 PooledMedian of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at BL32.7 Daily Minutes in Hypoglycemia
RZ358 PooledMedian of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at BL97.5 Daily Minutes in Hypoglycemia
RZ358 PooledMedian of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at 8 Weeks (EOT)99.1 Daily Minutes in Hypoglycemia
RZ358 PooledMedian of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at 8 Weeks (EOT)14.8 Daily Minutes in Hypoglycemia
RZ358 PooledMedian of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at 8 Weeks (EOT)46.0 Daily Minutes in Hypoglycemia
RZ358 PooledMedian of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at BL214 Daily Minutes in Hypoglycemia
Secondary

Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)

The median of average daily percent time in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\]), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia at baseline (BL) and end of treatment (EOT) is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at BL16.3 Daily Percent Time
RZ358 Cohort 1Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)12.3 Daily Percent Time
RZ358 Cohort 1Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at BL6.85 Daily Percent Time
RZ358 Cohort 1Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)5.13 Daily Percent Time
RZ358 Cohort 1Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at BL1.97 Daily Percent Time
RZ358 Cohort 1Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at 8 Weeks (EOT)1.27 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at BL3.57 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at 8 Weeks (EOT)1.05 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at BL20.3 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at BL8.75 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)3.25 Daily Percent Time
RZ358 Cohort 2Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)6.68 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)1.79 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at BL1.12 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at BL13.7 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at BL5.22 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)5.42 Daily Percent Time
RZ358 Cohort 3Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at 8 Weeks (EOT)0.61 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)7.35 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)20.4 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at BL19.5 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at 8 Weeks (EOT)1.27 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at BL3.03 Daily Percent Time
RZ358 Cohort 4Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at BL34.4 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at BL2.56 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at BL7.31 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)8.54 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at 8 Weeks (EOT)1.15 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)3.81 Daily Percent Time
RZ358 PooledMedian of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT)Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at BL16.2 Daily Percent Time
Secondary

Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)

The median of average hypoglycemia events per day at each of the specified glucose thresholds \[\<70, \<60, and \<50 mg/dL (3.9, 3.3, and 2.8 mmol/L)\], by CGM at baseline (BL) and end of treatment (EOT) is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at BL3.00 Hypoglycemia Events Per Day
RZ358 Cohort 1Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at 8 Weeks (EOT)2.37 Hypoglycemia Events Per Day
RZ358 Cohort 1Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at BL1.73 Hypoglycemia Events Per Day
RZ358 Cohort 1Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at 8 Weeks (EOT)1.54 Hypoglycemia Events Per Day
RZ358 Cohort 1Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at BL0.91 Hypoglycemia Events Per Day
RZ358 Cohort 1Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at 8 Weeks (EOT)0.74 Hypoglycemia Events Per Day
RZ358 Cohort 2Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at BL1.29 Hypoglycemia Events Per Day
RZ358 Cohort 2Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at 8 Weeks (EOT)0.53 Hypoglycemia Events Per Day
RZ358 Cohort 2Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at BL3.50 Hypoglycemia Events Per Day
RZ358 Cohort 2Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at BL2.22 Hypoglycemia Events Per Day
RZ358 Cohort 2Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at 8 Weeks (EOT)1.06 Hypoglycemia Events Per Day
RZ358 Cohort 2Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at 8 Weeks (EOT)1.70 Hypoglycemia Events Per Day
RZ358 Cohort 3Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at 8 Weeks (EOT)1.60 Hypoglycemia Events Per Day
RZ358 Cohort 3Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at BL0.79 Hypoglycemia Events Per Day
RZ358 Cohort 3Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at BL2.46 Hypoglycemia Events Per Day
RZ358 Cohort 3Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at BL1.77 Hypoglycemia Events Per Day
RZ358 Cohort 3Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at 8 Weeks (EOT)2.33 Hypoglycemia Events Per Day
RZ358 Cohort 3Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at 8 Weeks (EOT)0.60 Hypoglycemia Events Per Day
RZ358 Cohort 4Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at 8 Weeks (EOT)2.07 Hypoglycemia Events Per Day
RZ358 Cohort 4Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at 8 Weeks (EOT)3.33 Hypoglycemia Events Per Day
RZ358 Cohort 4Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at BL3.07 Hypoglycemia Events Per Day
RZ358 Cohort 4Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at 8 Weeks (EOT)1.00 Hypoglycemia Events Per Day
RZ358 Cohort 4Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at BL1.67 Hypoglycemia Events Per Day
RZ358 Cohort 4Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at BL4.47 Hypoglycemia Events Per Day
RZ358 PooledMedian of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at BL1.13 Hypoglycemia Events Per Day
RZ358 PooledMedian of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at BL2.00 Hypoglycemia Events Per Day
RZ358 PooledMedian of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at 8 Weeks (EOT)2.23 Hypoglycemia Events Per Day
RZ358 PooledMedian of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at 8 Weeks (EOT)0.64 Hypoglycemia Events Per Day
RZ358 PooledMedian of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at 8 Weeks (EOT)1.50 Hypoglycemia Events Per Day
RZ358 PooledMedian of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT)Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at BL3.37 Hypoglycemia Events Per Day
Secondary

Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)

The median of average weekly number of overall hypoglycemia events (\<70 mg/dL \[3.9mmol/L\], moderate hypoglycemia events (\<60 mg/dL \[3.3 mmol/L\] and severe hypoglycemia events (\<50 mg/dL \[2.8mmol/L\]) by SMBG at baseline (BL) and end of treatment (EOT) is reported.

Time frame: 8 weeks

Population: Per Protocol Population; For efficacy outcomes, the PP Population included 20 participants for BGM-based glycemic endpoints due to endpoint-specific exclusions. One participant in Cohort 1 and one in Cohort 4 were excluded from the PP population BGM-based analyses because they failed to meet pre-specified minimum testing frequency by glucometer. One participant in Cohort 3 was also excluded from the PP population BGM analyses for stopping background SOC therapy after starting RZ358 in the study

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at BL10.1 Hypoglycemia Events
RZ358 Cohort 1Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)9.92 Hypoglycemia Events
RZ358 Cohort 1Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at BL3.06 Hypoglycemia Events
RZ358 Cohort 1Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)6.42 Hypoglycemia Events
RZ358 Cohort 1Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at BL1.31 Hypoglycemia Events
RZ358 Cohort 1Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at 8 Weeks (EOT)1.17 Hypoglycemia Events
RZ358 Cohort 2Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at BL2.59 Hypoglycemia Events
RZ358 Cohort 2Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at 8 Weeks (EOT)0.94 Hypoglycemia Events
RZ358 Cohort 2Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at BL12.5 Hypoglycemia Events
RZ358 Cohort 2Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at BL6.69 Hypoglycemia Events
RZ358 Cohort 2Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)3.17 Hypoglycemia Events
RZ358 Cohort 2Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)6.60 Hypoglycemia Events
RZ358 Cohort 3Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)0.47 Hypoglycemia Events
RZ358 Cohort 3Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at BL3.50 Hypoglycemia Events
RZ358 Cohort 3Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at BL13.0 Hypoglycemia Events
RZ358 Cohort 3Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at BL9.00 Hypoglycemia Events
RZ358 Cohort 3Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)1.87 Hypoglycemia Events
RZ358 Cohort 3Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at 8 Weeks (EOT)0.00 Hypoglycemia Events
RZ358 Cohort 4Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)4.18 Hypoglycemia Events
RZ358 Cohort 4Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)7.60 Hypoglycemia Events
RZ358 Cohort 4Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at BL3.69 Hypoglycemia Events
RZ358 Cohort 4Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at 8 Weeks (EOT)0.52 Hypoglycemia Events
RZ358 Cohort 4Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at BL0.91 Hypoglycemia Events
RZ358 Cohort 4Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at BL9.30 Hypoglycemia Events
RZ358 PooledMedian of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at BL1.90 Hypoglycemia Events
RZ358 PooledMedian of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at BL5.99 Hypoglycemia Events
RZ358 PooledMedian of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)5.00 Hypoglycemia Events
RZ358 PooledMedian of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at 8 Weeks (EOT)0.49 Hypoglycemia Events
RZ358 PooledMedian of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)2.75 Hypoglycemia Events
RZ358 PooledMedian of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT)Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at BL11.5 Hypoglycemia Events
Secondary

Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)

The average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) is compared from baseline (BL) to end of treeatment (EOT) and the median percent change of that difference is reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureValue (MEDIAN)
RZ358 Cohort 1Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)7.59 Percent Change
RZ358 Cohort 2Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)3.67 Percent Change
RZ358 Cohort 3Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)-2.64 Percent Change
RZ358 Cohort 4Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)44.1 Percent Change
RZ358 PooledMedian Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)4.22 Percent Change
Secondary

Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)

The average duration (minutes) in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\] ), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia by CGM is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Overall Hypoglycemia (<70mg/dL; 3.9 mmol/L) from BL-22.2 Percent Change
RZ358 Cohort 1Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) from BL-18.6 Percent Change
RZ358 Cohort 1Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Moderate Hypoglycemia (<60mg/dL; 3.3mmol/L) from BL9.19 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Moderate Hypoglycemia (<60mg/dL; 3.3mmol/L) from BL-65.8 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Overall Hypoglycemia (<70mg/dL; 3.9 mmol/L) from BL-63.7 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) from BL-77.0 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Moderate Hypoglycemia (<60mg/dL; 3.3mmol/L) from BL-70.9 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Overall Hypoglycemia (<70mg/dL; 3.9 mmol/L) from BL-57.5 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) from BL-81.2 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Overall Hypoglycemia (<70mg/dL; 3.9 mmol/L) from BL-40.2 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) from BL-59.8 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Moderate Hypoglycemia (<60mg/dL; 3.3mmol/L) from BL-52.8 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Moderate Hypoglycemia (<60mg/dL; 3.3mmol/L) from BL-58.1 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Overall Hypoglycemia (<70mg/dL; 3.9 mmol/L) from BL-49.1 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) from BL-63.0 Percent Change
Secondary

Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)

The average daily percent time in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\]), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

Time frame: 8 weeks

Population: Per Protocol Population

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) from BL-31.1 Percent Change
RZ358 Cohort 1Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) from BL-21.9 Percent Change
RZ358 Cohort 1Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Moderate Hypoglycemia (<60mg/dL; <3.3 mmol/L) from BL-19.3 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Moderate Hypoglycemia (<60mg/dL; <3.3 mmol/L) from BL-65.9 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) from BL-64.6 Percent Change
RZ358 Cohort 2Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) from BL-74.4 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Moderate Hypoglycemia (<60mg/dL; <3.3 mmol/L) from BL-75.9 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) from BL-61.0 Percent Change
RZ358 Cohort 3Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) from BL-85.0 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) from BL-46.6 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) from BL-60.7 Percent Change
RZ358 Cohort 4Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Moderate Hypoglycemia (<60mg/dL; <3.3 mmol/L) from BL-53.9 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Moderate Hypoglycemia (<60mg/dL; <3.3 mmol/L) from BL-60.2 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) from BL-53.5 Percent Change
RZ358 PooledMedian Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL)Median Percent Change in Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) from BL-64.8 Percent Change
Secondary

Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)

The average weekly number overall hypoglycemia events (\<70 mg/dL \[3.9mmol/L\], moderate hypoglycemia events (\<60 mg/dL \[3.3 mmol/L\] and severe hypoglycemia events (\<50 mg/dL \[2.8mmol/L\]) by SMBG is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

Time frame: 8 weeks

Population: Per Protocol Population; For efficacy outcomes, the PP Population included 20 participants for BGM-based glycemic endpoints due to endpoint-specific exclusions. One participant in Cohort 1 and one in Cohort 4 were excluded from the PP population BGM-based analyses because they failed to meet pre-specified minimum testing frequency by glucometer. One participant in Cohort 3 was also excluded from the PP population BGM analyses for stopping background SOC therapy after starting RZ358 in the study

ArmMeasureGroupValue (MEDIAN)
RZ358 Cohort 1Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) from BL-1.6 Percent Change
RZ358 Cohort 1Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) from BL-40.3 Percent Change
RZ358 Cohort 1Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) from BL14.6 Percent Change
RZ358 Cohort 2Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) from BL-65.3 Percent Change
RZ358 Cohort 2Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) from BL-47.7 Percent Change
RZ358 Cohort 2Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) from BL-78.2 Percent Change
RZ358 Cohort 3Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) from BL-94.8 Percent Change
RZ358 Cohort 3Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) from BL-84.4 Percent Change
RZ358 Cohort 3Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) from BL-100 Percent Change
RZ358 Cohort 4Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) from BL-19.9 Percent Change
RZ358 Cohort 4Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) from BL-26.9 Percent Change
RZ358 Cohort 4Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) from BL20.8 Percent Change
RZ358 PooledMedian Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) from BL-64.4 Percent Change
RZ358 PooledMedian Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) from BL-58.9 Percent Change
RZ358 PooledMedian Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL)Median Percent Change of Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) from BL-78.2 Percent Change
Secondary

Occurrence of Hypoglycemia During Fasting Challenge

The occurrence of hypoglycemia during a 12 Hour fasting challenge.

Time frame: 8 Weeks

Population: Per Protocol Population

ArmMeasureGroupValue (NUMBER)
RZ358 Cohort 1Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at Baseline (n)3 participants
RZ358 Cohort 1Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at EOT (n)3 participants
RZ358 Cohort 2Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at Baseline (n)2 participants
RZ358 Cohort 2Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at EOT (n)1 participants
RZ358 Cohort 3Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at Baseline (n)0 participants
RZ358 Cohort 3Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at EOT (n)2 participants
RZ358 Cohort 4Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at EOT (n)1 participants
RZ358 Cohort 4Occurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at Baseline (n)0 participants
RZ358 PooledOccurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at Baseline (n)5 participants
RZ358 PooledOccurrence of Hypoglycemia During Fasting ChallengeNumber of patients able to complete fast at EOT (n)7 participants

Source: ClinicalTrials.gov · Data processed: Feb 5, 2026