Clinical trial NCT04259801: First Research Study to Look at How Two Medicines, NNC0480-0389 and Semaglutide, Work Together in Healthy People, in People With High Body Weight and in People With Diabetes
Official title: Investigation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of NNC0480-0389 in Combination With Semaglutide s.c.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Overweight
Obesity
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2020-02-06
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: Single ascending dose Part 2: Multiple ascending dose
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate how safe, and how well tolerated, the new study drug NNC0480-0389 is when it is given together with semaglutide. This will be investigated in healthy participants, participants with high bodyweight and participants with type 2 diabetes (T2D). NNC0480-0389 has not been given to humans before. It has been previously tested in the laboratory and on animals. NNC0480-0389 will be tested at various dose levels. Semaglutide is a new approved drug and is already available on the market for treatment of diabetes. It will also be investigated how quickly and to what extent NNC0480-0389 and semaglutide are taken up and eliminated from the body. This is called pharmacokinetics. The effect of NNC0480-0389 given together with semaglutide will also be investigated on body weight and glucose levels in the blood. This is called pharmacodynamics. The effects of NNC0480-0389 and/or semaglutide will be compared to the effects of a placebo. A placebo is a "dummy" medicine without any active medicine. Placebo looks like NNC0480-0389 and/or semaglutide. There are 4 possibilities for which treatment participants will get; participants will receive NNC0480-0389 and semaglutide or NNC0480-0389 and placebo or placebo with semaglutide, or placebo with placebo. Participants and the responsible doctor will not know which combination participants will be given. This is called a double-blinded study. However, this information can be looked up during the study if it is important for participants' health. The study medicines will be given as injections under the skin. Participants will be in the study for about 25 weeks.


Eligibility criteria: Inclusion Criteria:

Part 1:

* Male aged 18-45 years (both inclusive) at the time of signing informed consent.
* Body mass index between 20.0 kg/m\^2 and 29.9 kg/m\^2 (both inclusive).
* Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Part 2 (not applicable for proof-of-concept (PoC) cohort):

* Body mass index between 20.0 kg/m\^2 and 39.9 kg/m\^2 (both inclusive).
* Female of non-childbearing potential or male aged 18-55 years (both inclusive) at the time of signing informed consent.
* Considered to be eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Part 2 (only applicable for PoC cohort):

* Body mass index between 25.0 kg/m\^2 and 39.9 kg/m\^2 (both inclusive). Overweight or obesity should be due to excess adipose tissue, as judged by the investigator.
* Female of non-childbearing potential or male aged 18-64 years (both inclusive) at the time of signing informed consent.
* Considered to be eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.
* Diagnosed with type 2 diabetes at least 90 days prior to the day of screening.
* Subjects treated with diet and exercise as monotherapy or in combination with 1-2 of the following anti-diabetic drug(s) at a stable dose for at least 30 days prior to screening: metformin, sulfonylureas, meglitinides, DPP-4 inhibitors, alpha-glucosidase inhibitors, thiazolidinediones, GLP-1 receptor agonists or SLGT-2 inhibitors. The metformin dose should be between 1500 mg to 3000 mg or maximum tolerated or effective dose documented in subject's medical record.
* Glycosylated haemoglobin (HbA1c) in the range of 6.5% (inclusive) and 10% (non-inclusive).

Exclusion Criteria:

Part 1:

* Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
* HbA1c equal to or above 6.5 % (48 mmol/mol) at screening.
* Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of acetaminophen, ibuprofen and acetylsalicylic acid, or topical medication not reaching systemic circulation within 14 days prior to the day of screening. Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions.

Part 2 (not applicable for PoC cohort):

* Any disorder (except for conditions associated with T2D for the PoC cohort) which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
* Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions (except conditions associated with T2D for PoC Cohort).
* Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of acetaminophen, ibuprofen and acetylsalicylic acid, or topical medication not reaching systemic circulation within 14 days prior to the day of screening.
* HbA1c equal to or above 6.5 % (48 mmol/mol) at screening.

Part 2 (only applicable for PoC cohort):

* Any disorder (except for conditions associated with T2D for the PoC cohort) which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
* Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, or endocrinological conditions (except conditions associated with T2D for PoC Cohort).
* Use of any prohibited medications as listed in the protocol within 14 days of screening.
* Use of prescribed medications at the time of screening at a dose that had not been stable within 30 days prior to screening.

Primary outcomes:
measure: Number of treatment emergent adverse events (TEAE) in Part 1
timeFrame: From time of dosing (day 1) until completion of follow-up visit (day 71)
measure: Number of treatment emergent adverse events (TEAE) in Part 2
timeFrame: From first combination dosing (day 57) until completion of follow-up visit (day 148)
Secondary outcomes:
measure: Area under the NNC0480-0389 plasma concentration-time curve from time
timeFrame: From baseline (day 1) to post treatment follow-up (day 71)
measure: Maximum plasma concentration of NNC0480-0389 after administration of a single dose
timeFrame: From baseline (day 1) to post treatment follow-up (day 71)
measure: Area under the semaglutide plasma concentration time curve from time of dosing to infinity after administration of a single dose
timeFrame: From baseline (day 1) to post treatment follow-up (day 71)
measure: The maximum concentration of semaglutide after administration of a single dose
timeFrame: From baseline (day 1) to post treatment follow-up (day 71)
measure: Area under the NNC0480-0389 plasma concentration-time curve from 0 to 168 hours after administration of the 4th dose of NNC0480-0389 in week 12
timeFrame: From administration of dose in week 12 (day 78) to day 85
measure: Maximum plasma concentration of NNC0480-0389 after administration of the 4th dose of NNC0480-0389 in week 12
timeFrame: From administration of dose in week 12 (day 78) to post treatment follow-up (day 148)
measure: Area under the semaglutide plasma concentration-time curve from 0-168 hours after administration of the 12th dose of semaglutide
timeFrame: From administration of dose in week 12 (day 78) to day 85
measure: The maximum concentration of semaglutide after administration of the 12th dose of semaglutide
timeFrame: From administration of dose in week 12 (day 78) to post treatment follow-up (day 148)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor & Disclosure (1452)
role: STUDY_DIRECTOR
References: