Clinical trial NCT03751657: A Research Study to Compare Insulin 287 Once a Week to Insulin Glargine (100 Units/mL) Once a Day in People With Type 2 Diabetes.
Official title: An Investigational Trial Comparing the Efficacy and Safety of Once Weekly NNC0148-0287 C (Insulin 287) Versus Once Daily Insulin Glargine, Both in Combination With Metformin, With or Without DPP-4 Inhibitors, in Insulin naïve Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2018-11-23
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. The study participants will either get insulin 287 or insulin glargine (100 units/mL) - which treatment the participants get is decided by chance. The participants will need to inject their selves every day about the same time. Once a week the participant will need to take 1 extra injection on the same day of the week. The participants will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter using a finger prick, 2) write down different information in a paper diary daily and return this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2 weeks 5 times during the study.


Eligibility criteria: Inclusion Criteria:

* Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening
* HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory
* Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record) OR Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records)
* Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
* Body mass index (BMI) less than or equal to 40.0 kg/m\^2

Exclusion Criteria:

* Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation
* Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation
* Presently classified as being in New York Heart Association (NYHA) Class IV
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
* 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 pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation

Primary outcomes:
measure: Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: Change in HbA1c [Millimoles/Mole (mmol/Mol)]
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
Secondary outcomes:
measure: Change in Fasting Plasma Glucose
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: 9-point Profile (Individual SMPG Values)
timeFrame: Week 26 (Visit 28)
measure: Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
timeFrame: Week 26 (Visit 28)
measure: Fasting C-peptide
timeFrame: At week 26 (Visit 28)
measure: Change in Body Weight
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
timeFrame: week 25 (Visit 27) and 26 (Visit 28)
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: From baseline (Visit 2) to week 31 (Visit 30)
measure: Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: 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)
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: Number of Severe Hypoglycaemic Episodes (Level 3)
timeFrame: From baseline (Visit 2) to week 26 (Visit 28)
measure: Change in Anti-insulin 287 Antibody Titres
timeFrame: From baseline (Visit 2) to week 31 (Visit 30)
measure: Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
timeFrame: From baseline (Visit 2) to week 31 (Visit 30)
measure: Change in Anti-insulin 287 Antibody Level
timeFrame: From baseline (Visit 2) to week 31 (Visit 30)
Other outcomes:
Locations:
city: Lancaster
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Ventura
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Whiteville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Halifax
country: Canada
facility: Novo Nordisk Investigational Site
state: Nova Scotia
city: Brampton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Concord
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Etobicoke
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: St-Marc-des-Carrières
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Brno
country: Czechia
facility: Novo Nordisk Investigational Site
city: Pardubice
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 1
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 4
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 5
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 8
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha
country: Czechia
facility: Novo Nordisk Investigational Site
city: Rakovník
country: Czechia
facility: Novo Nordisk Investigational Site
city: Slaný
country: Czechia
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Bialystok
country: Poland
facility: Novo Nordisk Investigational Site
city: Gdansk
country: Poland
facility: Novo Nordisk Investigational Site
city: Lodz
country: Poland
facility: Novo Nordisk Investigational Site
city: Poznan
country: Poland
facility: Novo Nordisk Investigational Site
city: Warsaw
country: Poland
facility: Novo Nordisk Investigational Site
city: Wierzchoslawice
country: Poland
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Kosice
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Moldava nad Bodvou
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Sahy
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Trencin
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Koper
country: Slovenia
facility: Novo Nordisk Investigational Site
city: Ljubljana
country: Slovenia
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
citation: Rosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. PMID:32960514
citation: Rosenstock J, Bajaj HS, Janez A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R; NN1436-4383 Investigators. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. N Engl J Med. 2020 Nov 26;383(22):2107-2116. doi: 10.1056/NEJMoa2022474. Epub 2020 Sep 22.