Clinical trial NCT04795531: A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3)
Official title: A 26-week Double Blinded, Multiregional, Trial Comparing the Effect and Safety of Once Weekly Insulin Icodec and Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Non-insulin Anti-diabetic Drugs, in Insulin naïve Subjects With Type 2 Diabetes.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 588
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study compares insulin icodec (a new insulin taken once a week) to insulin degludec (an insulin taken once daily which is already available on the market) in people with type 2 diabetes.

The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin degludec taken daily.

Participants will get their study medicine in an injection pen. Participants will get a pen for weekly injection and one for daily injection. One will be icodec or degludec and the other will be dummy medicine. The treatment participants get is decided by chance. Participants and the study staff will not know which active medicine they get.

The insulin is injected with a needle in a skin fold in the thigh. The study could last for about 8 months. Participants will have 13 clinic visits and 17 phone calls with the study doctor. At 8 clinic visits participants will have blood samples taken. At 4 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.


Eligibility criteria: Inclusion Criteria:

* Male or female aged above or equal to 18 years at the time of signing informed consent.
* Diagnosed with T2D (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.
* HbA1c (glycated haemoglobin) from 7.0-11.0% (53.0-96.7 mmol/mol) both inclusive at screening confirmed by central laboratory analysis.
* 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.
* Stable daily dose(s) greater than or equal to 90 days prior to the day of screening of any of the following anti-diabetic drug(s) or combination regimen(s):

  a.) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. b.) Any metformin combination formulations greater than or equal to 1500 mg or maximum tolerated or effective dose. c.) Any of the following oral anti-diabetic drug classes including combinations (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose).:Sulfonylureas - Meglitinides (glinides) - DPP-4 inhibitors - SGLT2 inhibitors - Thiazolidinediones - Alpha-glucosidase inhibitors - Oral combination products (for the allowed individual Oral Anti-diabetic Drugs (OADs)) - Oral or injectable GLP-1-receptor agonists
* Body mass index (BMI) below or equal to 40.0 kg/m\^2.

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 (NYHA) 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.

Primary outcomes:
measure: Change in Glycated Haemoglobin (HbA1c)
timeFrame: Baseline (Week 0), Week 26
Secondary outcomes:
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Baseline (Week 0), Week 26
measure: Number of Severe Hypoglycaemic Episodes (Level 3)
timeFrame: From baseline (week 0) to week 31
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (< 3.0 mmol/L (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose [BG] Meter)
timeFrame: From baseline (week 0) to week 31
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 (week 0) to week 31
measure: Number of Severe Hypoglycaemic Episodes (Level 3)
timeFrame: From baseline (week 0) to week 26
measure: Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)
timeFrame: From baseline (week 0) to week 26
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 (week 0) to week 26
measure: Change in Body Weight
timeFrame: Baseline (Week 0), Week 26
measure: Mean Weekly Insulin Dose
timeFrame: From week 24 to week 26
Other outcomes:
Locations:
city: Guntersville
country: United States
facility: Lakeview Clinical Research, LLC
state: Alabama
city: Buena Park
country: United States
facility: American Clinical Trials
state: California
city: Escondido
country: United States
facility: Headlands Research California, LLC
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Lancaster
country: United States
facility: First Valley Medical Group
state: California
city: Jacksonville
country: United States
facility: Est Cst Inst for Rsrch,Jksnvil
state: Florida
city: Palm Harbor
country: United States
facility: Palm Harbor Medical Associates
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute Inc
state: Florida
city: Chicago
country: United States
facility: Cedar-Crosse Research Center
state: Illinois
city: Topeka
country: United States
facility: Cotton-Oneill Diabetes and End
state: Kansas
city: Troy
country: United States
facility: Arcturus Healthcare, PLC
state: Michigan
city: West Seneca
country: United States
facility: Southgate Medical Group, LLP
state: New York
city: Greenville
country: United States
facility: Physician's East Endocrinology
state: North Carolina
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Canton
country: United States
facility: Diab & Endo Assoc of Stark Co
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners Ctr
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Simpsonville
country: United States
facility: Hillcrest Clinical Research
state: South Carolina
city: Dallas
country: United States
facility: Velocity Clinical Res-Dallas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Med Cntr
state: Texas
city: Houston
country: United States
facility: PrimeCare Medical Group
state: Texas
city: Round Rock
country: United States
facility: Texas Diab & Endo, P.A.
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Saint George
country: United States
facility: Chrysalis Clinical Research
state: Utah
city: Renton
country: United States
facility: Rainier Clin Res Ctr Inc
state: Washington
city: Buenos Aires
country: Argentina
facility: STAT Research
city: Caba
country: Argentina
facility: Centro de Investigación Clínica
city: Caba
country: Argentina
facility: Medical Center of Diabetes and Nutrition
city: Mendoza
country: Argentina
facility: Instituto de Clínica Médica y Diabetes
city: Graz
country: Austria
facility: Universitätsklinik für Innere Medizin Graz
city: Graz
country: Austria
facility: Universitätsklinik für Innere Medizin
city: Linz
country: Austria
facility: Barmh. Brüder Linz, Konventspital
city: Wien
country: Austria
facility: Gesundheitszentrum Hetzendorf
city: Wien
country: Austria
facility: Hanusch-Krankenhaus, Wien
city: Curitiba
country: Brazil
facility: Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV
state: Parana
city: Curitiba
country: Brazil
facility: Centro de Diabetes Curitiba
state: Parana
city: Porto Alegre
country: Brazil
facility: Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda.
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica Ltda
state: Sao Paulo
city: Mount Pearl
country: Canada
facility: Commonwealth Medical Clinic
state: Newfoundland and Labrador
city: St. Johns
country: Canada
facility: Eastern Health Authority
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: LMC Diabetes & Endocrinology (Barrie)
state: Ontario
city: Brampton
country: Canada
facility: LMC ClinRsrh Inc.Brampton
state: Ontario
city: Concord
country: Canada
facility: LMC (Thornhill)
state: Ontario
city: Etobicoke
country: Canada
facility: LMC Endo Ctr (Etobicoke) Ltd
state: Ontario
city: London
country: Canada
facility: Western Univ. Cnt for Studies in Fam Med
state: Ontario
city: Nepean
country: Canada
facility: LMC Research Inc. Ottawa
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clin Res Group,Inc
state: Ontario
city: Toronto
country: Canada
facility: Centricity Research LMC
state: Ontario
city: Toronto
country: Canada
facility: Dr. Anil K Gupta Medicine Professional Corporation
state: Ontario
city: Brossard
country: Canada
facility: ViaCar Recherche Clinique Inc
state: Quebec
city: Montreal
country: Canada
facility: Clinique de Recherche Medpharmgene Inc.
state: Quebec
city: Saint-Laurent
country: Canada
facility: LMC Clin Rsrch Inc. (Montreal)
state: Quebec
city: Victoriaville
country: Canada
facility: Diex Recherche Victoriaville
state: Quebec
city: Beijing
country: China
facility: Chinese People's Liberation Army General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Pinggu Hospital
state: Beijing
city: ChongQing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Cangzhou
country: China
facility: Cangzhou People's Hospital
state: Hebei
city: Hengshui
country: China
facility: Harrison International Peace Hospital
state: Hebei
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital, Yanghu Branch
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University_Nanjing
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
state: Jiangsu
city: Zhenjiang
country: China
facility: The Affiliated Hospital of Jiangsu University_Zhenjiang
state: Jiangsu
city: Ji'nan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Tenth People's Hsopital, Tongji University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Fifth People's Hospital
state: Shanghai
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Broumov
country: Czechia
facility: Edumed Broumov
city: Pardubice
country: Czechia
facility: Diahelp - diabetologie
city: Plzeň 3
country: Czechia
facility: DIALINE s.r.o.
city: Praha 1
country: Czechia
facility: Diabet2 s.r.o.
city: Praha 5
country: Czechia
facility: EUC Klinika Praha a.s.
city: Praha 6
country: Czechia
facility: Fledip s.r.o.
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital Diabetes og Hormonsygdomme
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus Esbjerg
city: Hellerup
country: Denmark
facility: Steno Diabetes Center Cph_Steno Diabetes Center Cph
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital Endokrinologisk forsk. afs. 159
city: Le Coudray
country: France
facility: Les Hopitaux de Chartres-Hopital Louis Pasteur
city: Narbonne
country: France
facility: Centre Hospitalier de Narbonne
city: Paris
country: France
facility: Ap-Hp-Hopital Bichat-Claude Bernard-1
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon-Hopital Lyon Sud-1
city: Saint Herblain
country: France
facility: Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-3
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2
city: Venissieux
country: France
facility: Centre de Recherche Clinique Portes Du Sud
city: Guadalajara
country: Mexico
facility: Arechavaleta Granell María del Rosario
state: Jalisco
city: Hermosillo
country: Mexico
facility: Investigación Médica Sonora S.C.
state: Sonora
city: Bayamon
country: Puerto Rico
facility: Advanced Clinical Research LLC
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan City
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References:
citation: Philis-Tsimikas A, Bajaj HS, Begtrup K, Cailleteau R, Gowda A, Lingvay I, Mathieu C, Russell-Jones D, Rosenstock J. Rationale and design of the phase 3a development programme (ONWARDS 1-6 trials) investigating once-weekly insulin icodec in diabetes. Diabetes Obes Metab. 2023 Feb;25(2):331-341. doi: 10.1111/dom.14871. Epub 2022 Oct 14.