Treatment of Post-bariatric Hypoglycaemia
Condition: Hyperinsulinemic Hypoglycemia; Postprandial Hypoglycemia
MeSH terms: Congenital Hyperinsulinism; Nesidioblastosis; Hypoglycemia
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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:

        1. Subcutaneous placebo self-administration

        2. 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:

        1. Subcutaneous placebo self-administration

        2. Subcutaneous 120 µg dasiglucagon self-administration
    

Intervention name(s): Dasiglucagon; HyoPen; Placebo
Intervention type(s): Drug; Device; Drug
Intervention description(s): 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.; multi-dose reusable pen injector; 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.
Other intervention name(s): ZP4207; Zealand Pen
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 4 weeks x 4 weeks with an interposed washout period of 1 week
Masking: Double (Participant, Investigator)
Primary purpose: Treatment