Clinical trial NCT03789578: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2018-12-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a three-period cross-over trial. The treatments to be used are: Treatment A: insulin 287, Treatment B: semaglutide, and Treatment C: NNC0148-0287sema. The subjects will be randomised to one of the six treatment sequences in the trial: 1) ABC, 2) ACB, 3) BAC, 4) BCA, 5) CAB, and 6) CBA. The trial includes a screening visit followed by three 5 -week periods with pharmacokinetic sampling after single dose administration. The dose periods are separated by a 1-4 week washout period (from last pharmacokinetic sampling to next dosing). The follow-up period is 1-4 weeks after last pharmacokinetic sampling in period 3 (i.e. 6 to 9 weeks after last trial product administration). The total trial duration for the individual subjects participating in the trial will be 19 to 32 weeks (including follow-up), depending on individual visit schedules.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: AUCI287, 0-tz, area under the serum insulin 287 concentration-time curve from 0 hours to last quantifiable observation after a single dose
timeFrame: 0-840 hours
measure: AUCSema,0-tz, area under the plasma semaglutide concentration-time curve from 0 hours to last quantifiable observation after a single dose
timeFrame: 0-840 hours
Secondary outcomes:
measure: AUCI287,0-∞ area under the serum insulin 287 concentration-time curve from 0 hours to infinity after a single dose
timeFrame: 0-840 hours
measure: Cmax, I287, maximum observed serum insulin 287 concentration after a single dose
timeFrame: 0-840 hours
measure: tmax, I287, time to maximum observed serum insulin 287 concentration after a single dose
timeFrame: 0-840 hours
measure: AUCSema,0-∞, area under the plasma semaglutide concentration-time curve from 0 hours to infinity after a single dose
timeFrame: 0-840 hours
measure: Cmax,Sema, maximum observed plasma semaglutide concentration after a single dose
timeFrame: 0-840 hours
measure: tmax,Sema, time to maximum observed plasma semaglutide concentration after a single dose
timeFrame: 0-840 hours
measure: Number of treatment emergent adverse events
timeFrame: Day 1 (beginning of each period) to day 36 (end of each period)
measure: Number of hypoglycaemic episodes
timeFrame: Day 1 (beginning of each period) to day 36 (end of each period)
measure: Antibodies for insulin 287: Change in anti-insulin 287 binding antibody levels
timeFrame: Day -1 (pre-dose), Day 36 (end of period)
measure: Antibodies for insulin 287: Occurrence of anti-insulin 287 binding antibodies
timeFrame: Day 36 (end of period)
measure: Antibodies for insulin 287: Occurrence of anti-insulin 287 binding antibodies cross reacting to human insulin
timeFrame: Day 36 (end of period)
measure: Antibodies for semaglutide: Change in anti-semaglutide binding antibody levels
timeFrame: Day -1 (pre-dose), Day 36 (end of period)
measure: Antibodies for semaglutide: Occurrence of anti-semaglutide binding antibodies
timeFrame: Day 36 (end of period)
measure: Antibodies for semaglutide: Occurrence of anti-semaglutide binding antibodies cross reacting to endogenous glucagon-like peptide-1 (GLP-1)
timeFrame: Day 36 (end of period)
measure: Binding antibodies and in vitro neutralising antibodies (semaglutide only): Anti-semaglutide binding antibody levels
timeFrame: Day 151 (follow-up/end-of-trial visit)
measure: Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-semaglutide binding antibodies cross reacting to endogenous GLP-1
timeFrame: Day 151 (follow-up/end-of-trial visit)
measure: Binding antibodies and in vitro neutralising antibodies (semaglutide only): Anti-insulin 287 binding antibody levels
timeFrame: Day 151 (follow-up/end-of-trial visit)
measure: Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-insulin 287 binding antibodies cross reacting to human insulin
timeFrame: Day 151 (follow-up/end-of-trial visit)
measure: Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-semaglutide neutralising antibodies
timeFrame: Day 151 (follow-up/end-of-trial visit)
measure: Binding antibodies and in vitro neutralising antibodies (semaglutide only): Occurrence of anti-semaglutide neutralising antibodies cross reacting with endogenous GLP-1
timeFrame: Day 151 (follow-up/end-of-trial visit)
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
citation: Westergaard L, Alifrangis L, Buckley ST, Coester HV, Klitgaard T, Kristensen NR, Nishimura E, Norgreen L, Rocha TMP, Steensgaard DB, Vegge A, Plum-Morschel L. Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus. Clin Drug Investig. 2024 Nov;44(11):849-861. doi: 10.1007/s40261-024-01405-8. Epub 2024 Nov 3.