Clinical trial NCT03015220: Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes
Official title: Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD in Japanese Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-01-09
Enrollment: 458
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Asia. The aim of this trial is to investigate Safety and efficacy of oral semaglutide versus dulaglutide both in combination with one OAD (oral antidiabetic drug) in Japanese subjects with type 2 diabetes.


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
* Japanese male or female, age above or equal to 20 years at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus for at least 60 days prior to day of screening
* HbA1c (glycosylated haemoglobin) between 7.0%-10.5% (53-91 mmol/mol) (both inclusive)
* OAD (oral antidiabetic drug) monotherapy with stable daily dose for at least 60 days prior to the day of screening of one of SU (sulphonylurea) glinide , TZD (thiazolidinedione), α-GI (alpha-glucosidase inhibitor) or SGLT-2 (sodium-glucose cotransporter-2) inhibitor according to Japanese labelling

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives
* Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
* Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC)
* History 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 or hospitalisation for unstable angina or transient ischaemic attack (TIA) 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
* Subjects with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL)
* Renal impairment defined as estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)
* Treatment with once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) or once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor in a period of 90 days before the day of screening
* For subjects treated with an OAD other than TZD at screening: Treatment with TZD in a period of 90 days before the day of screening
* Treatment with any medication for the indication of diabetes or obesity in addition to background OAD medication (SU, glinide, TZD, α-GI or SGLT-2 inhibitor) in a period of 60 days before the day of screening with the exception of short-term insulin treatment for acute illness for a total of at least 14 days
* Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
* History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in situ carcinomas)
* History of diabetic ketoacidosis

Primary outcomes:
measure: Number of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Weeks 0-57
Secondary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, week 26, week 52
measure: Change in Fasting Plasma Glucose
timeFrame: Week 0, week 26, week 52
measure: Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile
timeFrame: Week 0, week 26, week 52
measure: Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All Meals
timeFrame: Week 0, week 26, week 52
measure: Change in Body Weight (kg)
timeFrame: Week 0, week 26, week 52
measure: Change in Body Weight (%)
timeFrame: Week 0, week 26, week 52
measure: Change in Body Mass Index (BMI)
timeFrame: Week 0, week 26, week 52
measure: Change in Waist Circumference
timeFrame: Week 0, week 26, week 52
measure: Change in Fasting Total Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Change in Fasting Low-density Lipoprotein (LDL) - Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Change in Fasting High-density Lipoprotein (HDL) - Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Change in Fasting Very-low Density Lipoprotein (VLDL) - Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Change in Fasting Triglyceride (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Participants Who Achieve HbA1c Below 7% (53 mmol/Mol), American Diabetes Association Target (Yes/No)
timeFrame: Week 26, week 52
measure: Participants Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target (Yes/No)
timeFrame: Week 26, week 52
measure: Participants Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/No)
timeFrame: Week 26, week 52
measure: Participants Who Achieve HbA1c Reduction More Than or Equal to 1% (10.9 mmol/Mol) and Weight Loss More Than or Equal to 3% (Yes/No)
timeFrame: Week 26, week 52
measure: Participants Who Achieve Weight Loss More Than or Equal to 5% (Yes/No).
timeFrame: Week 26, week 52
measure: Participants Who Achieve Weight Loss More Than or Equal to 10% (Yes/No)
timeFrame: Week 26, week 52
measure: Time to Additional Anti-diabetic Medication
timeFrame: Weeks 0-52
measure: Time to Rescue Medication
timeFrame: Weeks 0-52
measure: Change in Amylase (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Change in Lipase (Ratio to Baseline)
timeFrame: Week 0, week 26, week 52
measure: Change in Pulse Rate
timeFrame: Week 0, week 26, week 52
measure: Change in Blood Pressure
timeFrame: Week 0, week 26, week 52
measure: Change in ECG Evaluation
timeFrame: Week 0, week 26, week 52
measure: Change in Physical Examination
timeFrame: Week -2, week 26, week 52
measure: Change in Eye Examination Category
timeFrame: Week -2, week 52
measure: Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-57
measure: Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-57
measure: Change in SF-36v2 (Acute Version) Health Survey Scores: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)
timeFrame: Week 0, week 26, week 52
measure: Diabetes Therapy-Related Quality of Life (DTR-QoL): Total Score and Scores for the 4 Domains
timeFrame: week 0, week 26, week 52
Other outcomes:
Locations:
city: Adachi-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Annaka-shi, Gunma
country: Japan
facility: Novo Nordisk Investigational Site
city: Arakawa-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Chiba-shi, Chiba
country: Japan
facility: Novo Nordisk Investigational Site
city: Chuo-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukushima
country: Japan
facility: Novo Nordisk Investigational Site
city: Gunma
country: Japan
facility: Novo Nordisk Investigational Site
city: Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Iruma-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Kashiwara-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Kawagoe-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kawaguchi-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kumamoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Kurashiki-shi, Okayama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kyoto-shi, Kyoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Mitaka-shi, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Mito-shi, Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Miyazaki
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Ota-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Sendai-shi, Miyagi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shimotsuke-shi, Tochigi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shinagawa-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Shizuoka-shi, Shizuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Suita-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Toshima-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Yamato-shi, Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Ishii H, Hansen BB, Langer J, Horio H. Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial. Diabetes Ther. 2021 Feb;12(2):613-623. doi: 10.1007/s13300-020-00985-w. Epub 2021 Jan 18.
citation: Yabe D, Nakamura J, Kaneto H, Deenadayalan S, Navarria A, Gislum M, Inagaki N; PIONEER 10 Investigators. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020 May;8(5):392-406. doi: 10.1016/S2213-8587(20)30074-7.
citation: Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
citation: Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13.
citation: Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.