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. It will also be investigated how quickly and to what extent NNC0480-0389 and semaglutide are…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
SAD part
To investigate the safety and tolerability of single doses of NNC0480-0389
subcutaneously coadministered
with semaglutide in healthy male subjects.
MAD part
To investigate the safety and tolerability of multiple doses of NNC0480-0389
subcutaneously
co-administered with semaglutide in healthy subjects
Secondary outcome
SAD part
To investigate the pharmacokinetics of NNC0480-0389 upon subcutaneous
co-administration of single doses of NNC0480-0389 and semaglutide in healthy
male subjects
MAD part:
To investigate the pharmacokinetics of NNC0480-0389 upon subcutaneous
co-administration of multiple doses of NNC0480-0389 and semaglutide in healthy
subjects
MAD/POC part
To investigate the safety and tolerability of multiple doses of NNC0480-0389
subcutaneously co-administered with semaglutide in subjects with type 2
diabetes
To investigate the pharmacokinetics of NNC0480-0389 upon subcutaneous
co-administration of multiple doses of NNC0480-0389 and semaglutide in subjects
with type 2 diabetes
Background summary
People with diabetes have too much sugar in their blood and need treatment to
control their sugar level. The study drug (NNC0480-0389) acts like a hormone
called glucose-dependent insulinotropic peptide (GIP), which occurs naturally
in the human body. GIP is released by the intestines. Semaglutide is a newly
approved antidiabetic medicine that helps to lower blood sugar levels in
patients with type 2 diabetes. In addition to the treatment of type 2 diabetes,
semaglutide is currently also being developed for weight loss treatment for
obesity. NNC0480-0389 is being developed to be given together with
semaglutide. NNC0480-0389 targets a different part of the system that regulates
glucose levels in the body than semaglutide. Therefore, it is expected that
together NNC0480-0389 and semaglutide will more effectively lower glucose
levels in blood.
Study objective
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.
It will also be investigated how quickly and to what extent NNC0480-0389 and
semaglutide are taken up and eliminated from the body.
Study design
This first human dose trial is a two part, single-centre, placebo-controlled,
double-blinded, randomised, single ascending dose (SAD) and multiple ascending
dose (MAD) trial with a sequential trial design, and a proof-of-concept (PoC)
cohort. The study will be performed in 3 parts in a total of 156 healthy
participants, 60 healthy male participants (Part 1), 66 healthy male and female
participants (Part 2) and 30 male and female patients with type 2 diabetes
(Part 3).
Intervention
NNC0480-0389 (1.7, 8.6, 43 or 60 mg) and/or semaglutide (0.5 mg) and/or
placebo will be given as injections subcutaneous.
Study burden and risks
NNC0480-0389 has not been tested in humans before. Side effects have therefore
not been observed in humans and we do not know whether or how often these side
effects may happen.
- Hypersensitivity reactions
Hypersensitivity reactions may occur upon injection of a medicine.
Hypersensitivity reactions may show as local skin problems at the injection
site or allergic reactions.
Signs at the injection site may include:
- bruising
- pain and discomfort
- redness
- swelling
- itching
The problems usually go away after a few days.
Allergic reactions
Signs of mild allergic reactions may include:
- rash
- redness
- hives
- itching.
Signs of a serious allergic reaction may include:
- swelling of your throat, tongue and/or face
- trouble breathing
- wheezing
- fast heartbeat
- pale and cold skin
- feeling dizzy or weak.
Allergic reactions may become severe and can lead to shock and/or death if not
treated.
- Fast heartbeat
In animal studies a fast heartbeat has been seen for 1-2 days after receiving a
treatment with NNC0480-0389.
- Reddening of skin and gums
In animal studies reddening of skin or gums during treatment with NNC0480-0389
has been seen. This might be related to dilatation of small blood vessels which
has been reported as an effect of GIP.
- Low blood pressure
In animal studies a small lowering of blood pressure has been seen within 5-10
hours after treatment with NNC0480-0389.
Semaglutide
Semaglutide has been extensively studied in healthy volunteer. diabetic and
obese patients. The following side effects are most frequently observed (may
affect more than 1 out of 10 people):
Stomach and gut problems. Signs may include:
- feeling sick
- diarrhea
The stomach and gut problems are usually mild to moderate. These side effects
most often happen at the start of the treatment.
Possible discomforts due to procedures
During this study, small amounts of blood will be taken. This allows the study
doctor to see how the volunteer is doing and if the study medicine works.
- The volunteer may feel a little discomfort, bruising, bleeding or swelling
where the needle goes in.
- There is also a very small risk of infection where the needle goes in.
In total, we will take about 250 milliliters of blood from the volunteer. This
amount does not cause any problems in adults. To compare: a blood donation
involves 500 mL of blood being taken each time.
When making a recording of the electrical activity of your heart by an
electrocardiogram, the skin may react to the sticky electrode patches. Any skin
irritation usually disappears when the patches are removed.
A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. Taking the sample only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.
Novo Allé 1
Bagsvaerd 2880
DK
Novo Allé 1
Bagsvaerd 2880
DK
Listed location countries
Age
Inclusion criteria
SAD part
- Male aged 18-45 years (both inclusive) at the time of signing informed
consent.
- BMI between 20.0 kg/m2 and 29.9 kg/m2 (both inclusive).
MAD part (not applicable for PoC cohort)
- BMI between 20.0 kg/m2 and 29.9 kg/m2 (both inclusive).
- Female of non-childbearing potential or male aged 18-55 years (both
inclusive) at the time of signing informed consent.
MAD part (only applicable for PoC cohort)
- BMI between 25.0 kg/m2 and 39.9 kg/m2 (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.
-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 >= 1500 mg to <= 3000 mg or maximum tolerated or effective dose
documented in subject's medical record.
Exclusion criteria
- Any disorder (except for conditions associated with T2D for the PoC cohort
included in the MAD part) which in the investigator*s opinion might jeopardise
subject*s safety or compliance with the protocol.
- HbA1c >= 6.5 % (48 mmol/mol) at screening (except for MAD part only applicable
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
(except for the MAD part only applicable for PoC cohort).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002857-44-NL |
| CCMO | NL72389.056.19 |