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A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Registration Number
NCT05013229
Lead Sponsor
Novo Nordisk A/S
Brief Summary

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine taken daily with insulin aspart in people with type 2 diabetes.The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to insulin glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries.

Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach. The study will last for about 1 year and 1 month. Participants will be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study.

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
679
Inclusion Criteria
  • Male or female and age above or equal to 18 years at the time of signing informed consent.

  • Diagnosed with type 2 diabetes mellitus 180 days or more before screening.

  • HbA1c of 7.0-10.0 percentage (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.

  • Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses 90 days or more before screening:

    • Metformin
    • Sulfonylureas(a)
    • Meglitinides (glinides)(a)
    • DPP-4 inhibitors(a)
    • Sodium-glucose co-transporter 2 inhibitors
    • Alpha-glucosidase-inhibitors
    • Thiazolidinediones
    • Marketed oral combination products only including the products listed above.
  • Body mass index (BMI) less than or equal to 40.0 kg/m^2.

    1. Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation.
Exclusion Criteria
  • Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
  • Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid, hormones, or systemic corticosteroids).
  • Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
  • Any episodes of diabetic ketoacidosis within 90 days before screening. As declared by the participant or in the medical records.
  • Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
  • Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
  • Chronic heart failure classified as being in New York Heart Association Class IV at screening.
  • Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IcoSemaIcoSemaParticipants will receive once weekly subcutaneous (s.c) injections of IcoSema during the 52-week treatment period.
Insuling glargine/insulin aspartInsulin glargineParticipants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.
Insuling glargine/insulin aspartinsulin aspartParticipants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.
Primary Outcome Measures
NameTimeMethod
Change in HbA1cFrom baseline week 0 (V2) to week 52 (V54)

Percent-points

Secondary Outcome Measures
NameTimeMethod
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfactionFrom baseline week 0 (V2) to week 52 (V54)

Score 0-36. The higher the score the greater the satisfaction with treatment.

Change in body weightFrom baseline week 0 (V2) to week 52 (V54)

Kg

Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)From week 0 (V52) to week 52 (V54)

Number of episodes

Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6From week 48 (V50) to week 52 (V54)

Percentage of readings

Change in fasting plasma glucose (FPG)From baseline week 0 (V2) to week 52 (V54)

mmol/L

Weekly insulin dose (total)From week 50 (V52) to week 52 (V54)

Units

Number of severe hypoglycaemic episodes (level 3)From baseline week 0 (V2) to week 57 (V56)

Number of episodes

Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter)From baseline week 0 (V2) to week 57 (V56)

Number of episodes

Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6From week 48 (V50) to week 52 (V54)

Percentage of readings

Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6From week 48 (V50) to week 52 (V54)

Percentage of readings

Trial Locations

Locations (129)

Endeavor Health

🇺🇸

Skokie, Illinois, United States

Andres Garcia-Zuniga, MD, P.A

🇺🇸

Laredo, Texas, United States

Centre de Recherche Clinique Portes Du Sud

🇫🇷

Venissieux, France

University Technology MARA (UiTM) - Sg Buloh

🇲🇾

Sungai Buloh, Selangor, Malaysia

Centrum Terapii Współczesnej J.M. Jasnorzewska S.K.A.

🇵🇱

Lodz, Poland

Scripps Wht Diab Inst La Jolla

🇺🇸

La Jolla, California, United States

Downtown LA Res Ctr. Inc.

🇺🇸

Los Angeles, California, United States

San Diego Family Care

🇺🇸

San Diego, California, United States

Creekside Endocrine Associates

🇺🇸

Denver, Colorado, United States

Northeast Research Institute

🇺🇸

Fleming Island, Florida, United States

Northeast Res Inst. Inc.

🇺🇸

Jacksonville, Florida, United States

South Broward Research LLC

🇺🇸

Miramar, Florida, United States

Adult Medicine of Lake County, Inc.

🇺🇸

Mount Dora, Florida, United States

Florida Inst For Clin Res

🇺🇸

Orlando, Florida, United States

Endo Res Solutions Inc

🇺🇸

Roswell, Georgia, United States

Saltzer Medical Group Research

🇺🇸

Nampa, Idaho, United States

Iowa Diab & Endo Res Center

🇺🇸

West Des Moines, Iowa, United States

The Research Group of Lexington LLC

🇺🇸

Lexington, Kentucky, United States

MedStar Hlth Res Institute

🇺🇸

Hyattsville, Maryland, United States

Northern Pines Hlth Ctr, PC

🇺🇸

Buckley, Michigan, United States

Palm Research Center Inc-Vegas

🇺🇸

Las Vegas, Nevada, United States

Southern NH Diabetes and Endocrinology

🇺🇸

Nashua, New Hampshire, United States

Southgate Medical Group, LLP

🇺🇸

West Seneca, New York, United States

Piedmont Healthcare/Research

🇺🇸

Statesville, North Carolina, United States

Accellacare

🇺🇸

Wilmington, North Carolina, United States

Diab & Endo Assoc of Stark Co

🇺🇸

Canton, Ohio, United States

Prestige Clinical Research

🇺🇸

Franklin, Ohio, United States

New Venture Medical Research

🇺🇸

Wadsworth, Ohio, United States

Hillcrest Clinical Research

🇺🇸

Simpsonville, South Carolina, United States

AM Diabetes And Endocrinology Center

🇺🇸

Bartlett, Tennessee, United States

Univ Diab & Endo Consultants

🇺🇸

Chattanooga, Tennessee, United States

HealthStar Physicians PC

🇺🇸

Morristown, Tennessee, United States

Amarillo Med Spec LLP

🇺🇸

Amarillo, Texas, United States

Velocity Clinical Res-Dallas

🇺🇸

Dallas, Texas, United States

PlanIt Research, PLLC

🇺🇸

Houston, Texas, United States

Protenium Clinical Research

🇺🇸

Hurst, Texas, United States

Clinical Investigations Of Texas

🇺🇸

Plano, Texas, United States

Briggs Clinical Research, LLC

🇺🇸

San Antonio, Texas, United States

NE Clin Res of San Antonio

🇺🇸

San Antonio, Texas, United States

Simcare Medical Research, LLC

🇺🇸

Sugar Land, Texas, United States

Chrysalis Clinical Research

🇺🇸

Saint George, Utah, United States

Rainier Clin Res Ctr Inc

🇺🇸

Renton, Washington, United States

Fakultni nemocnice Plzen

🇨🇿

Plzen, Czech Republic, Czechia

University Hospital U sv. Anny

🇨🇿

Brno, Czechia

FN Hradec Kralove

🇨🇿

Hradec Kralove, Czechia

Diabet2 s.r.o.

🇨🇿

Praha 1, Czechia

Diabetologická a interní ambulance Diabet2

🇨🇿

Praha 1, Czechia

Fledip s.r.o.

🇨🇿

Praha, Czechia

ResTrial s.r.o.

🇨🇿

Praha 8, Czechia

III. interni klinika VFN a 1. LK UK v Praze

🇨🇿

Praha, Czechia

Institut klinicke a experimentalni mediciny_Praha

🇨🇿

Praha, Czechia

Centre Hospitalier Departemental Vendee- La Roche Sur Yon

🇫🇷

LA ROCHE-sur-YON cedex 9, France

Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-2

🇫🇷

Le Creusot, France

Aphp-Hopital Lariboisiere-1

🇫🇷

Paris, France

Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2

🇫🇷

Pessac, France

InnoDiab Forschung GmbH

🇩🇪

Essen, Germany

Wendisch/Dahl Hamburg

🇩🇪

Hamburg, Germany

Institut für Diabetesforschung GmbH Münster - Dr. med. Rose

🇩🇪

Münster, Germany

RED-Institut für medizinische Forschung und Fortbildung GmbH

🇩🇪

Oldenburg in Holstein, Germany

Zentrum für klinische Studien Alexander Segner

🇩🇪

Saint Ingbert-Oberwürzbach, Germany

Clinexpert Egészségügyi Szolgáltató és Kereskedelmi Kft.

🇭🇺

Budapest, Hungary

Szőcs Depot Egészségügyi Szolgáltató Kft.

🇭🇺

Budapest, Hungary

Semmelweis Egyetem II. Belgyógyászati Klinika

🇭🇺

Budapest, Hungary

ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.

🇭🇺

Budapest, Hungary

Békés Megyei Központi Kórház - dr. Réthy Pál Tagkórház

🇭🇺

Békéscsaba, Hungary

Apollo Hospital, Ahmedabad

🇮🇳

Ahmedabad, Gujarat, India

Apollo Hospital International Ltd

🇮🇳

Gandhinagar, Gujarat, India

Diacon Hospital Private Limited

🇮🇳

Bangalore, Karnataka, India

TOTALL Diabetes Hormone Institute

🇮🇳

Indore, Madhya Pradesh, India

Sahyadri Speciality Hospital

🇮🇳

Pune, Maharashtra, India

Sahyadri Super Speciality Hospital

🇮🇳

Pune, Maharashtra, India

chelleram Diabetes Institute

🇮🇳

Pune, Maharashtra, India

Post Graduate Institute of Medical Education & Research

🇮🇳

Chandigarh, Punjab, India

Christian Medical College and Hospital

🇮🇳

Ludhiana, Punjab, India

Fortis Heart Institute and Multispeciality Hospital

🇮🇳

Mohali, Punjab, India

Diabetes, Thyroid and Endocrine Centre

🇮🇳

Jaipur, Rajasthan, India

Madras Diabetes Research Foundation

🇮🇳

Chennai, Tamil Nadu, India

Christian Medical College Hospital, Vellore

🇮🇳

Vellore, Tamil Nadu, India

Medanta Lucknow Hospital

🇮🇳

Lucknow, Uttar Pradesh, India

Swasthya Diabetes Care

🇮🇳

Ahmedabad, India

Azienda Ospedaliero-Universitaria Renato Dulbecco

🇮🇹

Catanzaro, CZ, Italy

Pol. Uni. Campus Biomedico UOC Endocrinologia e Diabetologia

🇮🇹

Roma, RM, Italy

Azienda Ospedaliera Luigi Sacco

🇮🇹

Milano, Italy

Ospedale Civico Partinico di Palermo

🇮🇹

Partinico, Italy

IRCCS Multimedica

🇮🇹

Sesto San Giovanni (MI), Italy

Heiwadai Hospital

🇯🇵

Miyazaki-shi, Miyazaki, Japan

Asano Clinic

🇯🇵

Kawagoe-shi, Saitama, Japan, Japan

Tokyo Medical Univ. Hospital_Diabetes, Metabolism and Endocrinology

🇯🇵

Shinjuku-ku, Tokyo, Japan

TOSAKI Clinic for Diabetes and Endocrinology_Diabetes and Endocrinology

🇯🇵

Aichi, Japan

Akaicho Clinic

🇯🇵

Chiba-shi, Chiba, Japan

The Institute of Medical Science, Asahi Life Foundation

🇯🇵

Chuo-ku, Tokyo, Japan

Naka Kinen Clinic

🇯🇵

Ibaraki, Japan

Minami Akatsuka Clinic

🇯🇵

Mito-shi, Ibaraki, Japan

Takatsuki Red Cross Hospital

🇯🇵

Osaka, Japan

Tokyo-Eki Center-building Clinic

🇯🇵

Tokyo, Japan

Fukuwa Clinic

🇯🇵

Tokyo, Japan

Hospital Universiti Sains Malaysia_Kota Bharu, Kelantan

🇲🇾

Kota Bharu, Kelantan, Malaysia

Hospital Universiti Kebangsaan Malaysia

🇲🇾

Cheras, Kuala Lumpur, Malaysia

Hospital Seri Manjung

🇲🇾

Seri Manjung, Perak, Malaysia

University Technology MARA (UiTM) - Puncak Alam

🇲🇾

Sungai Buloh, Selangor, Malaysia

University Malaya Medical Centre

🇲🇾

Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia

Klinik Kesihatan Simpang Kuala

🇲🇾

Alor Setar, Malaysia

Miri Hospital

🇲🇾

Miri, Sarawak, Malaysia

NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska

🇵🇱

Bialystok, Podlaskie, Poland

Centrum Medyczne Pratia Gdynia

🇵🇱

Gdynia, Pomorskie, Poland

SNZOZ Lege Artis

🇵🇱

Bialystok, Poland

Gabinet Lekarski Malgorzata Saryusz-Wolska

🇵🇱

Lodz, Poland

NBR Polska Tomasz Klodawski

🇵🇱

Warszawa, Poland

Healthcare centre Kocevje

🇸🇮

Kocevje, Slovenia

Healthcare Centre Koper

🇸🇮

Koper, Slovenia

UKC Ljubljana, Endocrinology and Diabetes

🇸🇮

Ljubljana, Slovenia

General Hospital Murska Sobota

🇸🇮

Murska Sobota, Slovenia

General Hospital Nova Gorica_Diabetes

🇸🇮

Nova Gorica, Slovenia

Medi-Clinic Bloemfontein

🇿🇦

Bloemfontein, Free State, South Africa

Lenasia Clinical Trial Centre

🇿🇦

Lenasia, Gauteng, South Africa

Prof P. Joshi

🇿🇦

Pretoria, Gauteng, South Africa

Spoke Research Inc

🇿🇦

Cape Town, Western Cape, South Africa

Siriraj Hospital_Bangkoknoi, Bangkok

🇹🇭

Bangkoknoi, Bangkok, Bangkok, Thailand

Maharaj Nakorn Chiang Mai Hospital

🇹🇭

Chiang Mai, Mueang Chiang Mai District, Thailand

Rajavithi Hospital

🇹🇭

Bangkok, Thailand

Srinagarind Hospital

🇹🇭

Khon Kaen, Thailand

Maharat Nakhon Ratchasima Hospital

🇹🇭

Nakhon Ratchasima, Thailand

Baskent Universitesi Adana

🇹🇷

Adana, Turkey

Gulhane Egitim Arastirma Hastanesi

🇹🇷

Ankara, Turkey

Akdeniz University Tip Fakultesi Hastanesi

🇹🇷

Antalya, Turkey

Adnan Menderes Universitesi Uygulama ve Arastirma Hastanesi

🇹🇷

Aydin, Turkey

Pamukkale Universitesi Tip Fakultesi

🇹🇷

Denizli, Turkey

TC SB Ist.İl Sag.Müd.Prof.Dr.Cemil Tascioglu Sehir Hastanesi

🇹🇷

Istanbul, Turkey

Dokuz Eylul University Medical Faculty

🇹🇷

Izmir, Turkey

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