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Completed

NCT Number: NCT04836273

Treatment of Post-bariatric Hypoglycaemia

This is an investigator-initiated, proof-of-concept, randomised, double-blind, placebo-controlled, single-centre phase II study aiming to evaluate the efficacy, safety and tolerability of self-administered subcutaneous 120 µg dasiglucagon with an investigational trial device (i.e. a multi-dose reusable pen) for the treatment of postprandial hypoglycaemia after Roux-en-Y gastric bypass (RYGB) surgery. The study is divided into an in-patient and out-patient part.

The primary aim of the study is to compare the effects of self-administered 120 µg dasiglucagon versus placebo on continuous glucose monitoring (CGM)-assessed time spent in hypoglycaemia in RYGB-operated individuals in an out-patient setting.

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Key information

Conditions

Hyperinsulinemic Hypoglycemia Congenital Hyperinsulinism Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Glucose Metabolism Disorders Hyperinsulinism Hypoglycemia Infant, Newborn, Diseases Metabolic Diseases Nutritional and Metabolic Diseases Pancreatic Diseases Postprandial Hypoglycemia

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Hellerup, 2900, Denmark

About this study

Study design:

Before inclusion in the study, the participants will complete a screening visit and a blinded 14-day continuous glucose monitoring (CGM) run-in period to ascertain a regular occurrence of postprandial hypoglycaemia (IG <3.9 mmol/l, ≥3 times/week). After enrolment in the study, the participants will wear a CGM for the entirety of the study period (apart from the four weeks before the follow-up visit). Prior to the first mixed meal test (MMT) during the in-patient part, the subjects will be randomised into one of four double-blinded treatment sequences consisting of an in-patient part (two MMTs) follow by a nine weeks out-patient part (two times four weeks per out-patient part with an interposed washout period of one week) and ended with a follow-up visit four weeks after out-patient part completion.

During the in-patient part, the participants will undergo two separate MMTs, with a minimum of 7 days in-between, accompanied by one of the following double-blind, randomised, placebo-controlled crossover interventions:

  • Subcutaneous placebo self-administration
  • Subcutaneous 120 µg dasiglucagon self-administration

The out-patient part is divided into two double-blinded, randomised, placebo-controlled crossover out-patient parts with of the following interventions:

  • Subcutaneous placebo self-administration
  • Subcutaneous 120 µg dasiglucagon self-administration

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Documented postprandial hypoglycaemia (IG <3.9 mmol/l, ≥3 times/week) assessed by 14-days of blinded CGM recording
  • Haemoglobin levels for women >7.3 mmol/l and for men >8.3 mmol/l
  • Ferritin >10 μg/l
  • Cobalamin >150 pmol/l
  • Fasting plasma glucose concentration within the range of 4.0-6.0 mmol/l
  • Normal electrocardiogram (ECG)
  • Negative urine human chorionic gonadotropin (hCG) (for fertile women)

Exclusion criteria

  • Treatment with medication(s) affecting insulin secretion, glucose metabolism or any antidiabetic drugs
  • Treatment with antipsychotics
  • Current participation in another clinical trial with administration of investigational drug
  • Previous exposure to dasiglucagon (also known as ZP4207) within the last 30 days prior screening
  • History of liver disease that is expected to interfere with the anti-hypoglycaemic action of glucagon (e.g. liver failure or cirrhosis)
  • Pregnancy
  • Breastfeeding
  • Major surgery within 30 days before screening
  • Alcohol abuse (per investigator assessment)
  • Any factors that, in the opinion of the site principal investigator or clinical protocol chair, would interfere with the safe completion of the study, including medical conditions that may require hospitalization during the trial
  • History of pheochromocytoma or insulinoma
  • History of hypersensitivity or allergic reaction to dasiglucagon or any of the excipients
  • Known or suspected allergies to glucagon or related products

Treatment and study plan

Dasiglucagon

Drug

Abdominal s.c. self-administration 120 µg of dasiglucagon when blood glucose levels are below 3.9 mmol/L or interstitial glucose levels below 3.5 mmol/L. The frequency of the intervention is approximately once a day.

Other names: ZP4207

HyoPen

Device

multi-dose reusable pen injector

Other names: Zealand Pen

Placebo

Drug

Abdominal s.c. self-administration with placebo when blood glucose levels are below 3.9 mmol/L or interstitial glucose levels below 3.5 mmol/L. The frequency of the intervention is approximately once a day.

Primary outcomes

  1. Time spent in hypoglycaemia (IG < 3.9 mmol)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

    The primary endpoint is the percentage of time in hypoglycaemia (IG <3.9 mmol/l) assessed by CGM during the out-patient part.

Secondary outcomes

  1. Time (percent or minutes) spent in serious hypoglycaemia (IG <3.0 mmol/l)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  2. Frequency of hypoglycaemic events (IG <3.9 mmol/l and <3.0 mmol/l, respectively)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  3. Glycaemic time in range defined as: 1) hypoglycaemia (<3.9 mmol/l), 2) normoglycaemia (3.9-10.0 mmol/l), and 3) hyperglycaemia (>10.0 mmol/l)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  4. Frequency of hyperglycaemic events (IG >7.8 mmol/l and >10.0 mmol/l, respectively)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  5. Glycaemic variability assessed as coefficient of variance (CV)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  6. Glycaemic variability assessed as standard deviation (SD)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  7. Recovery of BG 15 minutes after trial drug administration (as measured by finger prick (BG >3.9 mmol/l))

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  8. Change in QoL as assessed by the World Health Organization's quality of life assessment (WHOQOL-BREF)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

    likert scale, zero (very poor) to five (very good)

  9. Change in hypoglycaemic symptoms will be evaluated by Edinburgh Hypoglycaemia Symptom Scale (EHSS)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

    likert scale, zero (not a all) to seven (a lot)

  10. Change in fear of hypoglycaemia as assessed by Hypoglycaemia Fear Scale (HFS-II)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

    likert scale, zero (never) to four (always)

  11. Change in administration frequency (as measured by percentage)

    Time frame: During the four weeks of placebo and dasiglucagon treatment.

  12. Nadir plasma glucose as assessed both as 1) absolute lowest value, and 2) a mean of three consecutive glucose measurements during the 240-minute MMT

    Time frame: Two hundred forty minutes of mixed meal test

    Nadir plasma glucose after the postprandial peak during the MMT in the in-patient part

  13. Recovery of BG 15 minutes after administration (as measured by finger prick (BG >3.9 mmol/l))

    Time frame: Two hundred forty minutes of mixed meal test

    After the postprandial peak during the MMT in the in-patient part

  14. Time spent in level 1 and level 2 hypoglycaemia (<3.9 and <3.0 mmol/l, respectively) from study drug administration until 240 minutes

    Time frame: Two hundred forty minutes of mixed meal test

    After the postprandial peak during the MMT in the in-patient part

  15. Glycaemic rescue intervention due to critically low plasma glucose concentration (<1.8 mmol/l)

    Time frame: Two hundred forty minutes of mixed meal test

    During the MMT in the in-patient part

  16. Time spent in hyperglycaemia (>7.8 mmol/l) from study drug administration until 240 minutes

    Time frame: Two hundred forty minutes of mixed meal test

    During the MMT in the in-patient part

  17. Peak plasma glucose concentration after study drug administration

    Time frame: Two hundred forty minutes of mixed meal test

    During the MMT in the in-patient part

  18. Counter-regulatory hormonal response

    Time frame: Two hundred forty minutes of mixed meal test

    Measured as area under the curve (AUC) and / or incremental (iAUC) as appropriate, peak values and values at nadir plasma glucose concentration during the MMT in the in-patient part. glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP)

  19. Changes in blood pressure

    Time frame: Two hundred forty minutes of mixed meal test

    During the MMT in the in-patient part

  20. Changes in heart rate

    Time frame: Two hundred forty minutes of mixed meal test

    During the MMT in the in-patient part

  21. Frequency and severity of adverse events (AE)s and serious adverse events (SAE)s from signed consent form to end of study (visit 4 / follow-up visit)

    Time frame: Through study completion which is an average of 16 weeks

    Safety endpoint

  22. Frequency and severity of adverse events (AE)s and serious adverse events (SAE)s during the in-patient part MMTs

    Time frame: During the in-patient part (MMTs) 0-240 minutes / Two hundred forty minutes of mixed meal test

    Safety endpoint

  23. Percentage (%) of participants with treatment-induced or treatment-boosted anti-dasiglucagon antibodies who did not have anti-dasiglucagon antibodies at baseline

    Time frame: Through study completion which is an average of 16 weeks

    Safety endpoint

  24. Device failures/ malfunctions occurring during the trial.

    Time frame: Through study completion which is an average of 16 weeks

    Device endpoint

Sponsors and collaborators

Lead sponsor

Filip Krag Knop

Other

Collaborators

  • Zealand Pharma

Registry information

Official study title

Ready-to-use Dasiglucagon for the Treatment of Postprandial Hypoglycaemia in Roux-en-Y Gastric Bypass Operated Patients

Acronym: SHERRY

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Apr 8, 2021
Registry last updated
Feb 2, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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