Clinical trial NCT04017832: A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes
Official title: China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-07-12
Enrollment: 1441
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 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and sitagliptin (a medicine doctors can already prescribe). Participants will either get oral semaglutide or sitagliptin - which treatment is decided by chance. Participants will get 2 tablets a day to take first thing in the morning on an empty stomach. Only 1 tablet has study medicine in it. The other tablet is a dummy medicine (placebo). After taking the semaglutide tablet, participants may not eat or drink anything for at least 30 minutes. After the 30 minutes, participants must take the sitagliptin tablet. Then participants can have their first meal of the day and take any other medicines they may need, including their metformin. The study will last for about 7 months (33 weeks). Participants will have 8 clinic visits and 1 phone call with the study doctor. At all 8 of the clinic visits, participants will have blood samples taken.


Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
* Male or female, age above or equal to 18 years at the time of signing informed consent.

For Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent.

For Taiwan only: Male or female, age above or equal to 20 years at the time of signing informed consent

* Diagnosed with type 2 diabetes mellitus 60 days or more prior to day of screening.
* HbA1c between 7.0-10.5% (53-91 mmol/mol) (both inclusive).
* Stable daily dose of metformin (equal to or above 1500 mg or maximum tolerated dose as documented in the subject medical record) 60 days or more prior to day of screening

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method (adequate contraceptive measure as required by local regulation or practice).
* Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC). Family is defined as a first degree relative.
* History or presence of pancreatitis (acute or chronic).
* History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
* Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation.
* Subjects presently classified as being in New York Heart Association (NYHA) Class IV.
* Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
* Renal impairment measured as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI).
* Subjects with alanine aminotransferase (ALT) above 2.5 x upper limit of the normal (ULN).
* 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. Fundus examination without dilation is only allowed if the digital camera used for fundus photography has this feature.
* Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.

Primary outcomes:
measure: Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%)
timeFrame: From baseline to week 26
Secondary outcomes:
measure: Change From Baseline to Week 26 in Fasting Plasma Glucose (FPG)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in 7 Point SMPG Profile: Mean Postprandial Increment (Over All Meals)
timeFrame: From baseline to week 26
measure: Number of Participants Who Achieved HbA1c <7.0 % (53 mmol/Mol) (American Diabetes Association [ADA] Target) (Yes/no)
timeFrame: At week 26
measure: Number of Participants Who Achieved HbA1c Equal to or Below 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no)
timeFrame: At week 26
measure: Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) (Yes/no)
timeFrame: At week 26
measure: Time to Rescue Medication
timeFrame: From baseline to week 31
measure: Change From Baseline to Week 26 in Body Weight (Kilogram [kg])
timeFrame: From baseline to week 26
measure: Percentage Change From Baseline to Week 26 in Body Weight
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Body Mass Index (BMI)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Waist Circumference
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Fasting Lipid Profile: Very-low-density Lipoprotein (VLDL) Cholesterol (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Fasting Lipid Profile: Triglycerides (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Fasting Lipid Profile: Free Fatty Acids (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey
timeFrame: From baseline to week 26
measure: Number of Participants Who Achieved Body Weight Loss Equal to or Above 3 Percent (Yes/no)
timeFrame: At week 26
measure: Number of Participants Who Achieved Body Weight Loss Equal to or Above 5 Percent (Yes/no)
timeFrame: At week 26
measure: Number of Participants Who Achieved Body Weight Loss Equal to or Above 10 Percent (Yes/no)
timeFrame: At week 26
measure: Number of Participants Who Achieved HbA1c Below 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no)
timeFrame: At week 26
measure: Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) and Body Weight Loss Equal to or Above 3 Percent (Yes/no)
timeFrame: At week 26
measure: Number of Treatment-emergent Adverse Events During Exposure to Trial Product
timeFrame: From baseline to week 31
measure: Number of Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product
timeFrame: From baseline to week 31
measure: Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Haematology Parameter: Haematocrit (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Haematology Parameter: Haemoglobin (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Haematology Parameter: Leucocytes (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Haematology Parameter: Thrombocytes (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Biochemistry Parameter: Calcium (Total) (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Biochemistry Parameter: Potassium (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Biochemistry Parameter: Sodium (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Biochemistry Parameter: Urea (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Biochemistry Parameter: Albumin (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Calcitonin (Ratio to Baseline)
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Vital Signs: Pulse Rate
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Vital Signs: Systolic Blood Pressure
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Vital Signs: Diastolic Blood Pressure
timeFrame: From baseline to week 26
measure: Change From Baseline to Week 26 in Electrocardiogram (ECG) Category
timeFrame: From baseline to week 26
measure: Physical Examination Category
timeFrame: Baseline and week 26
measure: Change From Baseline to Week 26 in Eye Examination Category
timeFrame: From baseline to week 26
measure: Number of Participants With Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product
timeFrame: From baseline to week 31
Other outcomes:
Locations:
city: Algiers
country: Algeria
facility: Maison des diabétiques El Harrach
city: Algiers
country: Algeria
facility: Department of internal medicine hospital (CHU) of BIRTRARIA
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: São Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas
state: Sao Paulo
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Shougang Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Pinggu Hospital
state: Beijing
city: Chongqing
country: China
facility: Second Affliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: 900th Hospital of Joint Logistics Support Force
state: Fujian
city: Quanzhou
country: China
facility: The Second Affiliated Hospital of Fujian Medical University
state: Fujian
city: Foshan
country: China
facility: Shunde Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen Universtiy
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Panyu Central Hospital
state: Guangdong
city: Huizhou
country: China
facility: Huizhou Central People's Hospital
state: Guangdong
city: Shantou
country: China
facility: The 2nd Affiliated Hospital of Shantou Uni Medical College
state: Guangdong
city: Cangzhou
country: China
facility: Cangzhou People's Hospital
state: Hebei
city: Hengshui
country: China
facility: Harrison International Peace Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Kaifeng
country: China
facility: Huaihe Hospital of Henan University
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan university of Science
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou First People's Hospital
state: Henan
city: Shiyan
country: China
facility: Taihe Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Puai Hosptial
state: Hubei
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou No.1 People's Hospital
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital Of University Of South China
state: Hunan
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital
state: Hunan
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital, Yanghu Branch
state: Jiangsu
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Sir Run Run Hospital Nanjing Medical University
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Zhenjiang
country: China
facility: The Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Province People's Hospital
state: Jilin
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Xining
country: China
facility: Qinghai Provincial People's Hospital
state: Qinghai
city: Xi'an
country: China
facility: The second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Jinan Central Hospital Affiliated to Shandong University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao Medical College
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Pudong New District
country: China
facility: Shanghai Pudong New Area People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Huashan Hospital, Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Tongji Hospital of Tongji university
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hsopital, Tongji University
state: Shanghai
city: Shanghai
country: China
facility: Dongfang Hospital Affiliated to Shanghai Tongji University
state: Shanghai
city: Shanghai
country: China
facility: The Fifth People's Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Tongren Hospital Shanghai Jiao Tong Univ. School of Medicine
state: Shanghai
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
state: Tianjin
city: Kunming
country: China
facility: First Affiated Hospital of Kunming Medical University
state: Yunnan
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The 2nd Affi Hosp of Zhejiang Univer School of Medicine
state: Zhejiang
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Brno
country: Czechia
facility: Nemocnice milosrdnych bratri
city: Chrudim
country: Czechia
facility: DIAMIN
city: Liberec
country: Czechia
facility: Interna a diabetologie MUDr. Vodickova
city: Praha 4
country: Czechia
facility: MUDr. Michala Pelikanova
city: Praha
country: Czechia
facility: CCR Prague
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Oradea
country: Romania
facility: SC Grand Med SRL
state: Bihor
city: Oradea
country: Romania
facility: S.C. Endodigest S.R.L.
state: Bihor
city: Timisoara
country: Romania
facility: SC Centru Medical Dr. Negrisanu SRL
state: Timis
city: Bucharest
country: Romania
facility: SC Nutrilife SRL
city: Constanta
country: Romania
facility: Clinic of Diabetes Constanta
city: Oradea
country: Romania
facility: Clinical County Emergency Hosp
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Dragisa Misovic
city: Belgrade
country: Serbia
facility: Endocrinology, Diabetes and Metabolism Diseases Clinic
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Zemun
city: Arcadia
country: South Africa
facility: GCT
state: Gauteng
city: Johannesburg
country: South Africa
facility: Dr R Dulabh
state: Gauteng
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research
state: Gauteng
city: Johannesburg
country: South Africa
facility: WITS Clinical Research
state: Gauteng
city: Kempton Park
country: South Africa
facility: Clinresco Centres (Pty) Ltd
state: Gauteng
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre
state: Gauteng
city: Brits
country: South Africa
facility: Armansis Medical Centre
state: North West
city: Kuilsriver
country: South Africa
facility: Cape Town Medical Research Centre
state: Western Cape
city: Paarl
country: South Africa
facility: Paarl Reserch Centre
state: Western Cape
city: Alberton
country: South Africa
facility: Union Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan city
country: Taiwan
facility: Chang Gung Medical Foundation - Linko Branch
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: