A Research Study to Look at How Insulin 287 and Semaglutide Work in the Body of People With Type 2 Diabetes When Taken Alone or Together

A Trial to Investigate Single Dose Pharmacokinetics of NNC0148-0287sema in a Fixed Ratio Compared With Insulin 287 and Semaglutide Given Separately in Subjects With Type 2 Diabetes

The study will look at how insulin 287 and semaglutide work in the body, both when given alone or together. This study will look at the way insulin 287 and semaglutide reach and stay in participants' blood after injection when given alone or together. Participants will get 3 study medicines at 3 different time points: 1) a combination of semaglutide plus insulin 287, 2) insulin 287 alone and 3) semaglutide alone. The order in which participants get them is decided by chance. Participants will get all medicines as an injection under the skin in the thigh. The injections will be done by study staff. The time between injections is 6 to 9 weeks. The study will last for about 19 to 32 weeks in total.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: NNC0148-0287sema; Drug: Semaglutide; Drug: NNC0148-0287

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female, aged 18-64 years (both inclusive) at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus more than or equal to 180 days prior to the day of screening
• Body weight between 80.0 to 120.0 kg (both inclusive)
• Glycosylated haemoglobin (HbA1c) 6.0 to 8.5% (both inclusive)
• No current and no regular previous intake of insulin. Previous insulin treatment for short periods of time (a maximum of 14 days) is allowed, as well as insulin use during a previous period of gestational diabetes in the past (as declared by the subject or reported in the medical records)
• Stable daily dose(s) of the following anti-diabetic drug(s)/regimen within the past 90 days prior to the day of screening: a) Any metformin formulation (dose as documented in the subject medical record), b) One other oral antidiabetic drug (dose as documented in the subject medical record) is allowed, but not mandatory: Insulin secretagogue (sulphonylureas), dipeptidyl peptidase 4 (DPP-4) inhibitor and sodium glucose co-transporter 2 (SGLT2) inhibitor

Exclusion Criteria:

• Known or suspected hypersensitivity to trial products or related products
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods
• Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event within the past 180 days) or hypoglycaemic unawareness as judged by the investigator or hospitalisation for diabetic ketoacidosis within the past 180 days prior to the day of screening
• Receipt of any investigational medicinal product within 90 days before screening
• History of severe allergies to drugs or foods or a history of severe anaphylactic reaction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide plus insulin 287; Participants will get a single dose of fixed-ratio combination of insulin 287 and semaglutide (NNC0148-0287sema (treatment C)).	Drug: NNC0148-0287sema; Study staff will inject NNC0148-0287sema, 175unit (U)/0.5 mg in the morning after fasting under the skin of participants' thigh using a needle and a pen.
Experimental: Semaglutide alone; Participants will get a single dose of semaglutide (treatment B) alone.	Drug: Semaglutide; Study staff will inject semaglutide, 0.5 mg alone in the morning after fasting under the skin of participants' thigh using a needle and a pen.; Other Names: Ozempic®
Experimental: Insulin 287 alone; Participants will get a single dose of insulin 287 (NNC0148-0287 (treatment A)) alone.	Drug: NNC0148-0287; Study staff will inject insulin 287 (NNC0148-0287), 175U alone in the morning after fasting under the skin of participants' thigh using a needle and a pen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCI287, 0-tz, area under the serum insulin 287 concentration-time curve from 0 hours to last quantifiable observation after a single dose	Measured in pmol*h/L for insulin 287 following administration of a fixed ratio of NNC0148-0287sema and insulin 287.	0-840 hours
AUCSema,0-tz, area under the plasma semaglutide concentration-time curve from 0 hours to last quantifiable observation after a single dose	Measured in pmol*h/L for semaglutide following administration of a fixed ratio of NNC0148-0287sema and semaglutide.	0-840 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCI287,0-∞ area under the serum insulin 287 concentration-time curve from 0 hours to infinity after a single dose	Measured in pmol*h/L for insulin 287 following administration of a fixed ratio of NNC0148-0287sema and insulin 287.	0-840 hours
Cmax, I287, maximum observed serum insulin 287 concentration after a single dose	Measured in pmol/L for insulin 287 following administration of a fixed ratio of NNC0148-0287sema and insulin 287.	0-840 hours
tmax, I287, time to maximum observed serum insulin 287 concentration after a single dose	Measured in hour (h) for insulin 287 following administration of a fixed ratio of NNC0148-0287sema and insulin 287.	0-840 hours
AUCSema,0-∞, area under the plasma semaglutide concentration-time curve from 0 hours to infinity after a single dose	Measured in pmol*h/L for semaglutide following administration of a fixed ratio of NNC0148-0287sema and semaglutide.	0-840 hours
Cmax,Sema, maximum observed plasma semaglutide concentration after a single dose	Measured in pmol/L for semaglutide following administration of a fixed ratio of NNC0148-0287sema and semaglutide.	0-840 hours
tmax,Sema, time to maximum observed plasma semaglutide concentration after a single dose	Measured in hour (h) for semaglutide following administration of a fixed ratio of NNC0148-0287sema and semaglutide.	0-840 hours
Number of treatment emergent adverse events	Count of events.	Day 1 (beginning of each period) to day 36 (end of each period)
Number of hypoglycaemic episodes	Count of episodes.	Day 1 (beginning of each period) to day 36 (end of each period)
Antibodies for insulin 287: Change in anti-insulin 287 binding antibody levels	Measured as percentage B/T following administration of NNC0148 -0287sema and insulin 287.	Day -1 (pre-dose), Day 36 (end of period)
Antibodies for insulin 287: Occurrence of anti-insulin 287 binding antibodies	Percentage of events (yes/no) following administration of NNC0148 -0287sema and insulin 287.	Day 36 (end of period)
Antibodies for insulin 287: Occurrence of anti-insulin 287 binding antibodies cross reacting to human insulin	Percentage of events (yes/no) following administration of NNC0148 -0287sema and insulin 287.	Day 36 (end of period)
Antibodies for semaglutide: Change in anti-semaglutide binding antibody levels	Measured as percentage B/T following administration of NNC0148 -0287sema	Day -1 (pre-dose), Day 36 (end of period)
Antibodies for semaglutide: Occurrence of anti-semaglutide binding antibodies	Percentage of events (yes/no) following administration of NNC0148 -0287sema.	Day 36 (end of period)
Antibodies for semaglutide: Occurrence of anti-semaglutide binding antibodies cross reacting to endogenous glucagon-like peptide-1 (GLP-1)	Percentage of events (yes/no) following administration of NNC0148 -0287sema.	Day 36 (end of period)
Binding antibodies and in vitro neutralising antibodies (semaglutide only): Anti-semaglutide binding antibody levels	Measured as percentage B/T.	Day 151 (follow-up/end-of-trial visit)
Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-semaglutide binding antibodies cross reacting to endogenous GLP-1	Percentage of events (yes/no).	Day 151 (follow-up/end-of-trial visit)
Binding antibodies and in vitro neutralising antibodies (semaglutide only): Anti-insulin 287 binding antibody levels	Measured as percentage B/T.	Day 151 (follow-up/end-of-trial visit)
Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-insulin 287 binding antibodies cross reacting to human insulin	Percentage of events (yes/no).	Day 151 (follow-up/end-of-trial visit)
Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-semaglutide neutralising antibodies	Percentage of events (yes/no).	Day 151 (follow-up/end-of-trial visit)
Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-semaglutide neutralising antibodies cross reacting with endogenous GLP-1	Percentage of events (yes/no).	Day 151 (follow-up/end-of-trial visit)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NN1535-4359; U1111-1204-8233 (Other Identifier: World Health Organization (WHO)); 2017-004538-27 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No