A Trial to Investigate Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of a Co-formulation of an Insulin Analog and Pramlintide in Subjects With Type 1 Diabetes Mellitus
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Adocia
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- CmaxPram
Study Overview
Brief Summary
This trial is a monocentric, randomised, double-blind, active comparator, controlled, 3-period cross-over trial.
Detailed Description
In this monocentric, randomised, double-blind, active comparator, controlled, cross-over trial, each patient will be randomly allocated to a sequence of three treatments: one single dose of the co-formulation of insulin analog and pramlintide (also called ADO09), simultaneous separate injections of pramlintide and human insulin and one single dose of insulin lispro. To keep the blinding in this trial, a placebo injection will be given in addition to the ADO09 formulation and insulin lispro dose for a total of 2 injections per dosing visit. During each visit, meal test procedures will be performed and subjects will stay at the clinical centre until post-dose follow-up period has been terminated. IMP administration will be done subcutaneously immediately prior to test meal intake.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 64 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Type 1 Diabetes Mellitus (as diagnosed clinically) ≥ 12 months
- •Treated with multiple daily injection ≥ 12 months
- •Treated with insulin glargine U100 or U300 or insulin detemir at screening
- •Fasting C-peptide ≤ 0.30 nmol/L
- •BMI: 18.5-28.0 kg/m² (both inclusive)
Exclusion Criteria
- •Known or suspected hypersensitivity to IMPs, paracetamol or related products
- •Type 2 Diabetes Mellitus
- •Clinically significant abnormal haematology, biochemistry or urinalysis screening test, as judged by the investigator considering the underlying disease
- •Presence of clinically significant acute gastrointestinal symptoms (e.g. nausea, vomiting, heartburn or diarrhoea), as judged by the investigator
- •Known slowing of gastric emptying, including gastroparesis and or gastrointestinal surgery that in the opinion of the investigator, might change gastrointestinal motility and food absorption
- •Intake of medication known to affect gastrointestinal motility, including but not limited to erythromycin, metoclopramide, cisapride, cholestyramine or colestipol within 4 weeks before screening
Arms & Interventions
Co-formulation of insulin analog and pramlintide (ADO09)
Subcutaneous injection of ADO09 formulation + injection of placebo (0.9% NaCl) to ensure double dummy.
Intervention: ADO09 formulation (Drug)
Co-formulation of insulin analog and pramlintide (ADO09)
Subcutaneous injection of ADO09 formulation + injection of placebo (0.9% NaCl) to ensure double dummy.
Intervention: Placebo (Drug)
Humulin® + Symlin®
Simultaneous, separate subcutaneous injections of human insulin and pramlintide.
Intervention: Symlin® (Drug)
Humulin® + Symlin®
Simultaneous, separate subcutaneous injections of human insulin and pramlintide.
Intervention: Humulin® (Drug)
Humalog®
Subcutaneous injection of insulin lispro + injection of placebo (0.9% NaCl) to ensure double dummy.
Intervention: Placebo (Drug)
Humalog®
Subcutaneous injection of insulin lispro + injection of placebo (0.9% NaCl) to ensure double dummy.
Intervention: Humalog® (Drug)
Outcomes
Primary Outcomes
CmaxPram
Time Frame: From 0 to 8 hours
Maximum pramlintide concentration
AUCPram 0-8h
Time Frame: From 0 to 8 hours
Area under the pramlintide concentration-time curve from 0-8 hours after IMP administration
CmaxIns
Time Frame: From 0 to 8 hours
Maximum insulin analog concentration
AUCIns 0-8h
Time Frame: From 0 to 8 hours
Area under the insulin analog concentration-time curve from 0-8 hours after IMP administration
Secondary Outcomes
- Pharmacokinetics of pramlintide(From 0 to 8 hours)
- Glucose pharmacodynamics(From 0 to 8 hours)
- Pharmacokinetics of insulins(From 0 to 8 hours)
- Safety and tolerability (Adverse Events recording)(From 0 to 8 hours)