A Trial to Investigate the Safety and the Pharmacokinetic, Pharmacodynamic Characteristics of Two BioChaperone® Glucagon Formulations Compared to Marketed GlucaGen® in Subjects With T1DM

• ClinicalTrials.gov Identifier: NCT03176524
• Recruitment Status: Completed
• First Posted: June 5, 2017
• Last Update Posted: December 12, 2017
• Sponsor: Adocia
• Information provided by (Responsible Party): Adocia

Study Description

Brief Summary:

This is a single centre, double-blind, randomised, three-period crossover phase 1 trial in subjects with type 1 diabetes mellitus (T1DM). Each subject will be randomly allocated to a sequence of three treatments, i.e. two single subcutaneous doses of BioChaperone® Glucagon (BC Glucagon) formulation 1, BioChaperone® Glucagon formulation 2 and GlucaGen® HypoKit®, each at the fixed doses of 50 µg and 1 mg on 3 separate dosing visits.

Following trial drug administration, pharmacokinetics (PK) and pharmacodynamics (PD) assessments will be carried until 4 hours. Safety will be assessed during all the trial period.

The total trial maximum duration for the individual subject will be up to 10 weeks.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: BioChaperone® glucagon formulation 1; Drug: BioChaperone® glucagon formulation 2; Drug: GlucaGen® HypoKit®	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Three-period Crossover Trial to Investigate the Safety and the Pharmacokinetic, Pharmacodynamic Characteristics of Two BioChaperone® Glucagon Formulations Compared to Marketed GlucaGen® in Subjects With Type 1 Diabetes
• Actual Study Start Date: June 6, 2017
• Actual Primary Completion Date: September 4, 2017
• Actual Study Completion Date: September 4, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: BioChaperone® glucagon formulation 1; Single subcutaneous fixed doses (50 µg and 1.0 mg)	Drug: BioChaperone® glucagon formulation 1; Injection of BioChaperone® glucagon formulation 1 at Day 1: 50 µg and at Day 2: 1 mg
Experimental: BioChaperone® glucagon formulation 2; Single subcutaneous fixed doses (50 µg and 1.0 mg)	Drug: BioChaperone® glucagon formulation 2; Injection of BioChaperone® glucagon formulation 2 at Day 1: 50 µg and at Day 2: 1 mg
Active Comparator: GlucaGen® HypoKit®; Single subcutaneous fixed doses (50 µg and 1.0 mg)	Drug: GlucaGen® HypoKit®; Injection of GlucaGen® HypoKit® at Day 1: 50 µg and at Day 2: 1 mg

Outcome Measures

Primary Outcome Measures :

1. Clinical safety laboratory [ Time Frame: Up to 10 weeks ]
   Haematology, biochemistry and urinalysis: changes or findings from baseline in clinical safety laboratory parameters during the trial duration (screening visit, treatment visits and follow up visit)
2. Physical examination [ Time Frame: Up to 10 weeks ]
   Examination of the body systems
3. ECG parameters [ Time Frame: Up to 10 weeks ]
   Heart rate, PQ, QRS, QT, QTcB: changes or findings from baseline in ECG parameters during the trial duration (screening visit, treatment visits and follow up visit)
4. Vital signs [ Time Frame: Up to 10 weeks ]
   Diastolic and systolic blood pressure (mmHg), Pulse (beats/min), Body temperature (°C), Respiratory frequency (RF/min): changes or findings from baseline in vital signs during the trial duration (screening visit, treatment visits and follow up visit)
5. Adverse events and serious adverse events [ Time Frame: Up to 10 weeks ]
   Untoward medical occurrence
6. Assessments of local tolerability at injection site [ Time Frame: Up to 10 weeks ]
   Local reaction at injection site

Secondary Outcome Measures :

1. AUCPK 0-30min [ Time Frame: From 0 to 30 min ]
   area under the baseline adjusted plasma glucagon concentration curve from 0 to 30 min
2. AUC PK 0-4h [ Time Frame: From 0 to 4 hours ]
   area under the baseline adjusted plasma glucagon concentration curve from 0 to 4 h
3. ΔAUCPG 0-30min [ Time Frame: From 0 to 30 min ]
   area under the baseline adjusted plasma glucose curve from 0 until 30 min
4. ΔAUCPG 0-4h [ Time Frame: From 0 to 4 hours ]
   area under the baseline adjusted plasma glucose curve from 0 until 4h
5. ΔPG 30min [ Time Frame: From 0 to 30 min ]
   baseline adjusted plasma glucose concentration at 30 min
6. Percentage of patients achieving a plasma glucose increase of ≥20 mg/dL from baseline within 30 minutes after treatment [ Time Frame: 30 min after drug administration ]
   only at day 2
7. Time to plasma glucose increase of ≥20 mg/dL from baseline [ Time Frame: Up to 4 hours after drug administration ]
   only at day 2

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female patients aged between 18 and 64 years (both inclusive)
• Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months prior to the screening visit
• Treated with daily insulin for T1DM ≥ 12 months prior to the screening visit
• Stable insulin treatment at least 3 months prior to the screening visit
• Stable disease with HbA1c <9.0 %
• C peptide <=0.30 nmol/L
• Body mass index (BMI) < 30.0 kg/m2

Exclusion Criteria:

• Type 2 Diabetes mellitus
• Previous participation in this trial. Participation is defined as being randomised
• Receipt of any medicinal product in clinical development within 60 days prior to this trial
• Clinically significant abnormal haematology, biochemistry, urinalysis, or coagulation screening tests, as judged by the Investigator considering the underlying disease
• Known or suspected hypersensitivity to the trial products or related products
• Severe hypoglycaemic events within one month prior to screening, as judged by the investigator
• Recent administration of glucagon (within 3 months prior to Screening)
• Clinically relevant diabetic complications as judged by the investigator
• Women of child bearing potential not willing to use contraceptive methods

Contacts and Locations

Locations

Germany

Profil Institut für Stoffwechselforschung GmbH

Neuss, Germany, 41460

Sponsors and Collaborators

Adocia

Investigators

• Principal Investigator: Ulrike Hövelmann, MD; Profil Institut für Stoffwechselforschung GmbH

More Information

• Responsible Party: Adocia
• ClinicalTrials.gov Identifier: NCT03176524
• Other Study ID Numbers: BC13-CT028
• First Posted: June 5, 2017
• Last Update Posted: December 12, 2017
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Glucagon; Glucagon-Like Peptide 1; Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Incretins