Dose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes

NCT ID: NCT03018028

Last Updated: 2021-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-10
• Study Completion Date: 2018-08-15

Brief Summary

This trial is conducted in Asia. The aim of this trial is to investigate the dose-response relationship of once-daily dosing of three dose levels (3, 7 and 14 mg) of oral semaglutide versus placebo as monotherapy on glycaemic control in Japanese subjects with type 2 diabetes mellitus

Conditions

Diabetes; Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Oral semaglutide 3 mg

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Oral administration once daily

Oral semaglutide 7 mg

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Oral administration once daily

Oral semaglutide 14 mg

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Oral administration once daily

Oral placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral administration once daily

Liraglutide 0.9 mg

Group Type: ACTIVE_COMPARATOR

Liraglutide

Intervention Type: DRUG

Subcutaneous (s.c., under the skin) injection once daily

Interventions

Semaglutide

Oral administration once daily

Intervention Type: DRUG

Placebo

Oral administration once daily

Intervention Type: DRUG

Liraglutide

Subcutaneous (s.c., under the skin) injection once daily

Intervention Type: DRUG

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 30 days prior to day of screening
• HbA1c 6.5%-9.5% (48-80 mmol/mol) (both inclusive) for subjects treated with oral antidiabetic drug as monotherapy and 7.0%-10.0% (53-86 mmol/mol) (both inclusive) for subjects treated with diet and exercise therapy alone
• Treatment for at least 30 days prior to day of screening with;- stable daily dose of oral anti-diabetic drug as monotherapy (allowed oral anti-diabetic drugs are: metformin, sulphonylurea, glinide, α-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor and sodium-glucose cotransporter-2 inhibitor) at a half-maximum approved dose or below according to Japanese labelling in addition to diet and exercise therapy. or - diet and exercise therapy alone

• 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)
• Initiation of anti-diabetic medication between the day of screening and the day of randomisation

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 and 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 within the past 180 days prior to the day of screening and randomisation
• Subject 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 agonist (GLP-1 RA), once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor or thiazolidinedione in a period of 90 days before the day of screening

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novo Nordisk Investigational Site

Akita-shi, Akita, , Japan

Novo Nordisk Investigational Site

Arakawa-ku, Tokyo, , Japan

Novo Nordisk Investigational Site

Ebina-shi, Kanagawa, , Japan

Novo Nordisk Investigational Site

Gunma, , Japan

Novo Nordisk Investigational Site

Kanagawa, , Japan

Novo Nordisk Investigational Site

Minato-ku, Tokyo, , Japan

Novo Nordisk Investigational Site

Naka, , Japan

Novo Nordisk Investigational Site

Osaka-shi, Osaka, , Japan

Novo Nordisk Investigational Site

Ota-ku, Tokyo, , Japan

Novo Nordisk Investigational Site

Saga-shi, Saga, , Japan

Novo Nordisk Investigational Site

Sendai-shi, Miyagi, , Japan

Novo Nordisk Investigational Site

Suita-shi, Osaka, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Countries

Japan

References

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.

Reference Type: DERIVED

PMID: 32998732 (View on PubMed)

Yamada Y, Katagiri H, Hamamoto Y, Deenadayalan S, Navarria A, Nishijima K, Seino Y; PIONEER 9 investigators. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020 May;8(5):377-391. doi: 10.1016/S2213-8587(20)30075-9.

Reference Type: DERIVED

PMID: 32333875 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32267058 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31903692 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1181-4048

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-173489

Identifier Type: OTHER

Identifier Source: secondary_id

NN9924-4281

Identifier Type: -

Identifier Source: org_study_id