Primary objectiveTo demonstrate the effect on glycaemic control of once weekly insulin icodec in combination with insulin aspart, with or without non-insulin anti-diabetic drugs, in subjects with T2D on a basal-bolus regimen. This includes comparing…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in HbA1c (%) from baseline week 0 (V2) to week 26 (V28)
Secondary outcome
Secondary efficacy endpoints
* Change in fasting plasma glucose from baseline week 0 (V2) to week 26 (V28)
* Time in target-range 3.9*10.0 mmol/L (70-180 mg/dL) from week 22 (V24) to
week 26 (V28)
Secondary safety endpoints
* Number of severe hypoglycaemic episodes (level 3) from baseline week 0 (V2)
to week 31 (V30)
* Number of clinically significant hypoglycaemic episodes (level 2) (<3.0
mmol/L (54 mg/dL), confirmed by BG meter) from baseline week 0 (V2) to week 31
(V30) * Number of clinically significant hypoglycaemic episodes (level 2) (<3.0
mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes
(level 3) from baseline week 0 (V2) to week 31 (V30)
* Time spent < 3.0 mmol/L (54 mg/dL) from week 22 (V24) to week 26 (V28)
* Time spent > 10 mmol/L (180 mg/dL) from week 22 (V24) to week 26 (V28)
* Mean weekly insulin dose from week 24 (V26) to week 26 (V28)
* Change in body weight from baseline week 0 (V2) to week 26 (V28)
Background summary
T2D is characterised by insulin resistance, impaired insulin secretion,
increased hepatic glucose output due to glucagon dysregulation resulting in
chronic hyperglycaemia. The pathogenesis is not fully understood but seems to
be heterogeneous, involving environmental, lifestyle, and genetic factors
leading to chronic hyperglycaemia caused by peripheral tissue insulin
resistance, impaired insulin secretion due to abnormal beta-cell function and
abnormal glucose metabolism in the liver. The current treatment cascade follows
a stepwise approach comprising lifestyle changes in combination with
pharmacological intervention. In many countries, metformin is recommended as
initial pharmacological therapy, followed by combination therapy with other
oral anti-diabetic drugs, glucagon-like peptide 1 receptor agonists (GLP-1 RA)
and/or insulin as the disease progresses. On average, after failure of diet and
exercise alone, subjects require a new intervention with glucose-lowering
agents every 3-4 years in order to obtain/retain good glycaemic control.
Clinical inertia, often resulting from a resistance to insulin initiation and
intensification, is a major contributing factor to subjects with T2D who are
not achieving recommended glycaemic targets. Increased convenience is believed
to support timely insulin initiation and intensification in the treatment for
T2D.
Study objective
Primary objective
To demonstrate the effect on glycaemic control of once weekly insulin icodec in
combination with insulin aspart, with or without non-insulin anti-diabetic
drugs, in subjects with T2D on a basal-bolus regimen. This includes comparing
the difference in change from baseline in HbA1c between insulin icodec and
insulin glargine after 26 weeks of treatment to a non-inferiority limit of 0.3%.
Secondary objective
To compare safety with once weekly insulin icodec versus once daily insulin
glargine, both in combination with insulin aspart, with or without non-insulin
anti-diabetic drugs, in subjects with T2D on a basal-bolus regimen.
Study design
A 26-week trial comparing the effect and safety of once weekly insulin icodec
and once daily insulin glargine 100 units/mL, both in combination with bolus
insulin with or without non-insulin anti-diabetic drugs, in subjects with type
2 diabetes on a basal-bolus regimen.
Intervention
Subjects will be randomised (1:1) to receive once weekly insulin icodec or once
daily insulin glargine, both in combination with 2-4 times daily injections of
insulin aspart. Insulin icodec, insulin glargine and insulin aspart are all
administered as a subcutaneous injection.
Study burden and risks
Insulin icodec is efficacious at clinically relevant doses. Titration guidance
for phase 3a trials aims to achieve good glycaemic control without increasing
the risk of hypoglycaemic events.
No new significant safety information that changes the current benefit*risk
profile of insulin icodec emerged from the ongoing and completed clinical
trials. The safety profile of insulin icodec remains in line with the
cumulative experience.
As an overall assessment, Novo Nordisk evaluates that the benefit*risk balance
of insulin icodec remains favourable.
Considering the measures taken to minimise risk to subjects participating in
this trial, the potential risks identified in association with insulin icodec
are justified by the anticipated benefits that may be afforded to subjects with
diabetes mellitus.
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Flemingweg 8
Alphen aan den Rijn 2408AV
NL
Listed location countries
Age
Inclusion criteria
- Male or female aged above or equal to 18 years at the time of signing
informed consent.
- Diagnosed with T2D * 180 days prior to the day of screening.
- HbA1c from 7.0-10.0% (53.0-85.8 mmol/mol) both inclusive at screening
confirmed by central laboratory analysis.
- Treated with once daily basal insulin (neutral protamine hagedorn insulin,
insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin
glargine 300 units/mL) and 2-4 daily injections of bolus insulin analog
(insulin aspart, faster acting insulin aspart, insulin lispro, faster acting
insulin lispro, insulin glulisine) * 90 days prior to the day of screening with
or without any of the following anti-diabetic drugs/regimens with stable doses
* 90 days prior to screening:
* Metformin
* Sulfonylureas
* Meglitinides (glinides)
* DPP-4 inhibitors
* SGLT2 inhibitors
* Thiazolidinediones
* Alpha-glucosidase inhibitors
* Oral combination products (for the allowed individual oral anti-diabetic
drugs)
* Oral or injectable GLP-1 RAs
- Body mass index (BMI) * 40.0 kg/m2
Exclusion criteria
- Any episodes (as declared by the subject or in the medical records) of
diabetic ketoacidosis within 90 days prior to the day of screening.
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris
or transient ischaemic attack within 180 days prior to the day of screening.
- Chronic heart failure classified as being in New York Heart Association Class
IV at screening.
- Anticipated initiation or change in concomitant medications (for more than 14
consecutive days) known to affect weight or glucose metabolism (e.g. treatment
with orlistat, thyroid hormones, or corticosteroids).
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy.
Verified by a fundus examination performed within the past 90 days prior to
screening or in the period between screening and randomisation. Pharmacological
pupil-dilation is a requirement unless using a digital fundus photography
camera specified for non-dilated examination.
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 | EUCTR2020-000474-16-NL |
| CCMO | NL75121.018.20 |