Efficacy and Safety of Dasiglucagon for Treatment of Post-bariatric Hypoglycemia in Roux-en-Y Gastric Bypass (RYGB) Operated Adults

A Double-Blind, Placebo-Controlled, Cross-over Trial, Evaluating Efficacy and Safety of Dasiglucagon for Treatment of Post-bariatric Hypoglycemia in Roux-en-Y Gastric Bypass (RYGB) Operated Adults

The objective of the trial is to assess the effect of single subcutaneous doses of dasiglucagon versus placebo on post-prandial plasma glucose nadir following a Mixed Meal Test in Roux-en-Y Gastric Bypass (RYGB) subjects

Study Overview

• Status: Withdrawn
• Conditions: Glucose Metabolism Disorders; Hypoglycemia
• Intervention / Treatment: Drug: Dasiglucagon; Drug: Dasiglucagon; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previously undergone Roux-en-Y gastric bypass (RYGB) surgery at least 6 months prior to screening
• Previous diagnosis of post-bariatric hypoglycemia (PBH), requiring intake of oral carbohydrates.
• Body mass index (BMI) ≤ 40 kg/m2
• Fasting plasma glucose between 72-106 mg/dL (4.0-6.0 mmol/l)

Exclusion Criteria:

• History of hypersensitivity reactions to glucagon or dasiglucagon or any of the excipients
• History of insulinoma, pheochromocytoma, MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease.
• Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m2 or end-stage renal disease at screening
• Hepatic disease, including serum alanine aminotransferase or aspartate aminotransferase ≥ 2.5 times the upper limit of normal (ULN)
• Active malignancy, except for basal or squamous cell skin cancers
• History of a cerebrovascular accident within 6 months prior to screening
• History of myocardial infarction, unstable angina, or revascularization within 6 months prior to screening.
• Congestive heart failure, New York Heart Association Class III or IV
• Concurrent administration of β-blocker therapy
• Clinically significant ECG abnormalities at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Dasiglucagon high dose, followed by placebo, followed by dasiglucagon low dose	Drug: Dasiglucagon; dasiglucagon SC, low dose; Drug: Dasiglucagon; dasiglucagon SC, high dose; Drug: Placebo; placebo for dasiglucagon
Experimental: Sequence 2; Dasiglucagn low dose, followed by dasiglucagon high dose, followed by placebo	Drug: Dasiglucagon; dasiglucagon SC, low dose; Drug: Dasiglucagon; dasiglucagon SC, high dose; Drug: Placebo; placebo for dasiglucagon
Experimental: Sequence 3; Placebo, followed by dasiglucagon low dose, followed by dasiglucagon high dose	Drug: Dasiglucagon; dasiglucagon SC, low dose; Drug: Dasiglucagon; dasiglucagon SC, high dose; Drug: Placebo; placebo for dasiglucagon
Experimental: Sequence 4; Dasiglucagon high dose, followed by dasiglucagon low dose, followed by placebo	Drug: Dasiglucagon; dasiglucagon SC, low dose; Drug: Dasiglucagon; dasiglucagon SC, high dose; Drug: Placebo; placebo for dasiglucagon
Experimental: Sequence 5; Placebo, followed by dasiglucagon high dose, followed by dasiglucagn low dose	Drug: Dasiglucagon; dasiglucagon SC, low dose; Drug: Dasiglucagon; dasiglucagon SC, high dose; Drug: Placebo; placebo for dasiglucagon
Experimental: Sequence 6; Dasiglucagon low dose, followed by placebo, followed by dasiglucagon high dose	Drug: Dasiglucagon; dasiglucagon SC, low dose; Drug: Dasiglucagon; dasiglucagon SC, high dose; Drug: Placebo; placebo for dasiglucagon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Nadir plasma glucose concentration	From trial drug administration to 240 minutes after initiation of Mixed Meal Test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent time spent in hypoglycemia	Defined as time with a plasma glucose value of 70 mg/dL (3.9 mmol/L) or less	From trial drug administration to 240 minutes after initiation of Mixed Meal Test
Percent time spent in clinical significant hypoglycemia	Defined as time with a plasma glucose value of 54 mg/dL (3.0 mmol/L) or less	From trial drug administration to 240 minutes after initiation of Mixed Meal Test
Percent time spent in target range	Defined as time with a plasma glucose value of 70-180 mg/dL (3.9-10.0 mmol/L)	From trial drug administration to 240 minutes after initiation of Mixed Meal Test
Percent time spent in hyperglycemia	Defined as time with a plasma glucose value >180 mg/dL (>10 mmol/l)	From trial drug administration to 240 minutes after initiation of Mixed Meal Test

Collaborators and Investigators

• Sponsor: Zealand Pharma

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: March 29, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemia; Metabolic Diseases; Glucose Metabolism Disorders
• Other Study ID Numbers: ZP4207-20123

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No