Dose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes (PIONEER 9)

Novo Nordisk

Status and phase: Completed; Phase 3

Conditions: Diabetes; Diabetes Mellitus, Type 2

Treatments: Drug: Semaglutide; Drug: Placebo; Drug: Liraglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03018028

U1111-1181-4048 (Other Identifier)

JapicCTI-173489 (Other Identifier)

NN9924-4281

Details and patient eligibility

About

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

Enrollment: 243 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

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
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 60 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 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)
• Initiation of anti-diabetic medication between the day of screening and the day of randomisation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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243 participants in 5 patient groups, including a placebo group

Oral semaglutide 3 mg

Experimental group

Treatment:

Drug: Semaglutide

Oral semaglutide 7 mg

Experimental group

Treatment:

Drug: Semaglutide

Oral semaglutide 14 mg

Experimental group

Treatment:

Drug: Semaglutide

Oral placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Liraglutide 0.9 mg

Active Comparator group

Treatment:

Drug: Liraglutide