Clinical trial NCT04109547: A Research Study Comparing a New Medicine Oral Semaglutide to Placebo in People With Type 2 Diabetes
Official title: China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-09-30
Enrollment: 521
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: The study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and placebo (a dummy medicine). Researchers will test semaglutide to see how well it works compared to placebo. The study will also test if semaglutide is safe. Participants will either get semaglutide or placebo - which treatment is decided by chance. Participants will get 1 tablet a day to take with up to half a glass of water. Participants must take the tablet first thing in the morning on an empty stomach. After taking the tablet, participants must not eat or drink anything for at least 30 minutes. After the 30 minutes, participants can have their first meal of the day and take any other medicines they may need. The study will last for about 8 months (36 weeks). Participants will have 9 clinic visits and 2 phone calls with the study doctor. At all 9 of the clinic visits, participants will have blood samples taken. At 5 of the clinic visits, participants must arrive fasting. This means they cannot eat for 8 hours before the visit. It is fine to drink water up to 2 hours before the visit. This is for some of the blood samples that will be taken at the visit. Women cannot take part if pregnant, breastfeeding or planning to become pregnant during the study period.


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 the informed consent.

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

* Diagnosed with type 2 diabetes mellitus
* HbA1c between 7.0 -10.0% (53-86 mmol/mol) (both inclusive).

Exclusion Criteria:

* - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an highly effective contraceptive method.
* 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.
* 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).
* 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 in Glycosylated Haemoglobin (HbA1c)
timeFrame: Baseline (Week 0), Week 26
Secondary outcomes:
measure: Change From Baseline in Body Weight (Kilograms [kg])
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting 7-point Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting 7-point Self-measured Plasma Glucose Profile: Mean Postprandial Increment (Over All Meals)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Body Weight (Percentage [%])
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Waist Circumference
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Fasting Lipid Profile: Triglycerides (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey
timeFrame: Baseline (Week 0), Week 26
measure: Number of Participants Who Achieved HbA1c Less Than (<) 7.0 % (53 Millimoles Per Mole [mmol/Mol]) (American Diabetes Association (ADA) Target) (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved HbA1c Reduction Greater Than or Equal to (>=) 1 Percent (10.9 mmol/Mol) (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved Body Weight Loss >= 3 Percent (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved Body Weight Loss >= 5 Percent (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved Body Weight Loss >= 10 Percent (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved HbA1c < 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or Blood Glucose [BG] Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no)
timeFrame: Week 26
measure: Number of Participants Who Achieved HbA1c Reduction >= 1% (10.9 mmol/Mol) and Body Weight Loss >= 3 Percent (Yes/no)
timeFrame: Week 26
measure: Time From First Dose to Initiation of Rescue Medication
timeFrame: From baseline (Week 0) to Week 26
measure: Semaglutide Plasma Concentrations
timeFrame: Week 26: post dose any time
measure: Change From Baseline in Haematology - Haematocrit (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Haematology - Haemoglobin (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Haematology - Leucocytes (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Haematology - Thrombocytes (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Urea (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Creatinine (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Alanine Aminotransferase (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Aspartate Aminotransferase (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Alkaline Phosphatase (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Total Bilirubin (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Amylase (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Lipase (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Biochemistry - Creatine Kinase (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Calcium (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Potassium (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Sodium (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Albumin (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Calcitonin (Ratio to Baseline)
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Systolic Blood Pressure
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Diastolic Blood Pressure
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Electrocardiogram (ECG) Category
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Physical Examination Category
timeFrame: Baseline (Week 0), Week 26
measure: Change From Baseline in Eye Examination Category
timeFrame: Baseline (Week 0), Week 26
measure: Number of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 31 weeks
measure: Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Up to 31 weeks
measure: Number of Participants With Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Up to 31 weeks
measure: Anti-semaglutide Binding Antibody Levels
timeFrame: Up to 31 weeks
measure: Number of Participants With Anti-semaglutide Binding Antibodies
timeFrame: Up to 31 weeks
measure: Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1
timeFrame: Up to 31 weeks
Other outcomes:
Locations:
city: Algiers
country: Algeria
facility: Bouzareah Diabetic House Algiers Algeria
city: Algiers
country: Algeria
facility: UH of Douera
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Pinggu Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
state: Beijing
city: Chongqing
country: China
facility: Second Affliated Hospital of Chongqing Medical University
state: Chongqing
city: ChongQing
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Fuzhou
country: China
facility: 900th Hospital of Joint Logistics Support Force
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen Universtiy
state: Guangdong
city: Guangzhou
country: China
facility: The 3rd Affiliated Hospital of Guangzhou Medical University
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: Handan
country: China
facility: Handan First 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: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Shiyan
country: China
facility: Taihe Hospital
state: Hubei
city: Changde
country: China
facility: The First People's Hospital of Changde City
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou No.1 People's Hospital
state: Hunan
city: Yueyang
country: China
facility: Yueyang Central Hospital
state: Hunan
city: Changzhou
country: China
facility: Changzhou No.2 People's Hospital, Yanghu Branch
state: Jiangsu
city: Huai'an
country: China
facility: The Second People Hospital of Huai'an
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: 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: Jiaxing
country: China
facility: The First Hospital of Jiaxing
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: The first hospital of Jilin University
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: Yinchuan
country: China
facility: People's Hospital of Ningxia Hui Autonomous Region
state: Ningxia
city: Xining
country: China
facility: Qinghai University Affiliated 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: Jining
country: China
facility: The Affiliated Hospital of Jining Medical University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao Medical College
state: Shandong
city: Pudong New District
country: China
facility: Shanghai Pudong New Area People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Rui Jin Hospital,Shanghai Jiao Tong University School of Med
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: 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: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
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: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Budapest
country: Hungary
facility: Szent Margit Rendelőintézet Nonprofit Kft.
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Kórház
city: Tatabánya
country: Hungary
facility: Szent Borbála Kórház
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Nis
country: Serbia
facility: Clinical Centre Nis, Endocrinology, Diabetes and Metabolism
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan city
country: Taiwan
facility: Chang Gung Medical Foundation - Linko Branch
city: Dnipro
country: Ukraine
facility: Clinic of Medical Academy, Dnipro
city: Khmelnytskyi
country: Ukraine
facility: CNI "Khmelnytskyi regional hospital" of KRC
city: Kyiv
country: Ukraine
facility: Institute of Endocrinology and Metabolism of AMSU
city: Mykolaiv
country: Ukraine
facility: City Hospital #1
city: Poltava
country: Ukraine
facility: CI "1st City Clinical Hospital of Poltava City Council"
city: Ternopil
country: Ukraine
facility: CNI "Ternopil University Clinic" of Ternopil Regio. Council
city: Zaporizhia
country: Ukraine
facility: Zaporizhia Regional Clinical Endocrinology Dispensary
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: