First Research Study to Compare a Possible New Medicine NNC9204-1513 to the Medicine Glucagon, in Healthy People.

• ClinicalTrials.gov Identifier: NCT03444467
• Recruitment Status: Completed
• First Posted: February 23, 2018
• Last Update Posted: September 5, 2018
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

The study is comparing the new medicine NNC9204-1513 with a standard therapy of glucagon (GlucaGen®). This is the first time NNC9204-1513 is given to humans.

Participants will either receive NNC9204-1513 or GlucaGen® - which treatment you get is decided by chance (like flipping a coin). Neither the participant nor the study doctor will know which study medicine (NNC9204-1513 or GlucaGen®) the participant is receiving (double -blinding). In case of emergency, this information will be readily available.

NNC9204-1513 is a new medicine for rescue treatment of severe low blood sugar and currently not available on the market (doctors cannot prescribe this medicine). The participant will receive two or three single injections below the skin. One injection will contain NNC9204-1513 or GlucaGen®. The other injection will include placebo - this is a product that looks like the actual study drug but without any active ingredients. If a third injection is given, this will contain NNC9204-1513 or placebo. NNC9204-1513 and GlucaGen® will be given using different devices and volumes. In order to mask these external differences, a "double dummy" approach will be used, that means when you get either of the study medicine (NNC9204-1513 or GlucaGen®) you will get another injection which contains no medicine called 'placebo' (it will not have any effect on the body). Dependent on the injection volume to be administered, injections are given by either syringe with needle or an injection pen (NovoPen Echo®). The study will last for up to 39 days.

Condition or disease	Intervention/treatment	Phase
Diabetes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2	Drug: NNC9204-1513; Drug: Glucagon; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blinded, Single Subcutaneous Dose Escalation Trial Investigating the Safety and Tolerability of NNC9204-1513 in Healthy Subjects
• Actual Study Start Date: February 5, 2018
• Actual Primary Completion Date: May 24, 2018
• Actual Study Completion Date: May 24, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: NNC9204-1513; Participants will receive increasing doses of NNC9204-1513.	Drug: NNC9204-1513; Participants will receive NNC9204-1513 subcutaneous (s.c., in to a skin fold on the stomach) injection as single increasing doses of 0.01 mg, 0.04 mg, 0.10 mg, 0.25 mg, 0.50 mg, 1.0 mg or 2.0 mg. Each participant will only be given one dose. Dose escalation will proceed to the next planned dose level if there are no safety concerns raised by the investigator or by the trial safety group.; Drug: Placebo; Participants will receive single dose of placebo (for double dummy injections).
Active Comparator: Glucagon; Participants will receive a single fixed dose of glucagon.	Drug: Glucagon; Participants will receive single dose of 1 mg glucagon s.c. injection.; Other Name: GlucaGen®; Drug: Placebo; Participants will receive single dose of placebo (for double dummy injections).

Outcome Measures

Primary Outcome Measures :

1. Number of treatment emergent adverse events (TEAEs) [ Time Frame: from time of dosing (day 1) to completion of the safety follow-up visit (day 8) ]
   Count of events

Secondary Outcome Measures :

1. Change from baseline in haematology [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
2. Change from baseline in biochemistry [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
3. Change from baseline in fibrinogen [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
   measured in g/L
4. Change from baseline in lipids [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
5. Change from baseline in glucose metabolism [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
6. Change from baseline in hormones [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
7. Change from baseline in urine dipstick parameter [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
8. Change from baseline in systolic- and diastolic blood pressure [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
   Measured in mm Hg
9. Change from baseline in body temperature [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
10. Change from baseline in respiration rate [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
11. Change from baseline in 12-lead electrocardiogram (ECG) heart rate [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
12. Change from baseline in 12-lead ECG (RR interval) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
13. Change from baseline in 12-lead ECG (PR interval) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
14. Change from baseline in 12-lead ECG (QRS interval) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
15. Change from baseline in 12-lead ECG (QT interval) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
16. Change from baseline in 12-lead ECG (QTc intervals [Fridericia]) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
    QT interval corrected for heart rate by Fridericia's formula
17. Change from baseline in Physical examination [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
18. Incidence of injection site reactions [ Time Frame: After administration of the trial products (day 1) until completion of the post-treatment follow-up visit (day 8). ]
19. AUC0-15min,SD, area under the plasma concentration time curve [ Time Frame: 0 to 15 minutes after single dose ]
20. t1/2,SD, terminal half-life [ Time Frame: Measured for 24 hours after administration of a single s.c. dose ]
21. Onset of appearance [ Time Frame: Measured for 24 hours after administration of a single s.c. dose ]
    Time from trial product administration until first time plasma concentration ≥ lower limit of quantification (LLOQ)
22. AUCPG,0-15min,SD, area under the plasma glucose time curve [ Time Frame: 0 to 15 minutes after single dose ]
23. ΔPG0-15min,SD, Increase in plasma glucose concentration from 0 to 15 minutes [ Time Frame: 0 to 15 minutes after single dose ]
    Calculated as: Plasma glucose concentration at 15 minutes after single dose minus plasma glucose concentration at 0 minute
24. Change from baseline in 12-lead ECG (overall evaluation) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
25. Change from baseline in prothrombin time [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
    measured in seconds
26. Change from baseline in Activated Partial Thromboplastin time (APTT) [ Time Frame: baseline (day 1), follow-up visit (day 8) ]
    measured in seconds

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male, aged 18 -55 years (both inclusive), at the time of signing informed consent
• Body mass index (BMI) between 18.5 and 28.0 kg/sqm (both inclusive)
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, ECG and clinical laboratory tests performed during the screening visit, as judged by the investigator

Exclusion Criteria:

• Any disorder which in the investigator's opinion might jeopardise subject's safety, evaluation of results, or compliance with the protocol
• Smoker (defined as a subject who is smoking at least one cigarette or equivalent daily) who is not able or willing to refrain from smoking and use of nicotine substitute products during the inpatient period
• Any blood draw in excess of 25 mL in the past month, or donation of blood or plasma in excess of 400 mL within the 3 months preceding screening

Contacts and Locations

Locations

Germany

Novo Nordisk Investigational Site

Berlin, Germany, 10117

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

More Information

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03444467
• Other Study ID Numbers: NN9513-4290; U1111-1180-8217 ( Other Identifier: World Health Organization (WHO) ); 2016-001173-33 ( Registry Identifier: European Medicines Agency (EudraCT) )
• First Posted: February 23, 2018
• Last Update Posted: September 5, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://www.novonordisk-trials.com/

• 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.: Yes

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Glucagon; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs