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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 January 2021
• Main ID: NCT03018028
• Date of registration: 06/01/2017
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: 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
• Scientific title: Dose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes
• Date of first enrolment: January 10, 2017
• Target sample size: 243
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03018028
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Japan

Key inclusion & exclusion 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, a-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



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Diabetes

Diabetes Mellitus, Type 2

Intervention(s)

Drug: Semaglutide

Drug: Liraglutide

Drug: Placebo

Primary Outcome(s)

Change in HbA1c (Week 26) [Time Frame: Week 0, week 26]

Secondary Outcome(s)

Change in ECG Evaluation [Time Frame: Week 0, week 26, week 52]

Change in Total Cholesterol (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) [Time Frame: Week 0 - 57]

Anti-semaglutide Neutralising Antibodies (Yes/no) [Time Frame: Week 0 - 57]

Change in Amylase (Ratio to Baseine) [Time Frame: Week 0, week 26, week 52]

Change in Blood Pressure [Time Frame: Week 0, week 26, week 52]

Change in Body Weight (%) [Time Frame: Week 0, week 26 and week 52]

Change in Body Weight (kg) [Time Frame: Week 0, week 26, week 52]

Change in Eye Examination Category [Time Frame: Week -8, Week 52]

Change in Fasting C-peptide (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile [Time Frame: Week 0, week 26, week 52]

Change in Triglycerides (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes [Time Frame: Week 0 - 57]

Change in Fasting Pro-insulin (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in Fasting Pro-insulin/Insulin Ratio (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) [Time Frame: Week 0 - 57]

Change From Baseline in DTR-QOL: Sub-domains [Time Frame: Week 0, week 26, week 52]

Change in Mean Postprandial Increment Over All Meals in SMPG [Time Frame: Week 0, week 26 and week 52]

Change in VLDL Cholesterol (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in LDL Cholesterol (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in Lipase (Ratio to Baseine) [Time Frame: Week 0, week 26, week 52]

Change From Baseline in DTR-QOL: Total Score [Time Frame: Week 0, week 26, week 52]

Change in Body Mass Index [Time Frame: Week 0, week 26 and week 52]

Change in Fasting Glucagon (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in Fasting Plasma Glucose [Time Frame: Week 0, week 26, week 52]

Change in SF-36: Sub-domains [Time Frame: Week 0, week 26, week 52]

Participants Who Achieved HbA1c Reduction Above or Equal to 1% (10.9 mmol/Mol) and Weight Loss Above or Equal to 3% [Time Frame: Week 26 and week 52]

Anti-semaglutide Binding Antibodies (Yes/no) [Time Frame: Week 0 - 57]

Change in Fasting Insulin (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Time to Rescue Medication [Time Frame: Weeks 0 - 52]

Change in Physical Examination [Time Frame: Baseline (Week -8), week 26, week 52]

Participants Who Achieved Weight Loss Above or Equal to 5% (Yes/No) [Time Frame: Week 26 and week 52]

Change in SF-36: Physical Component Summary (PCS) [Time Frame: Week 0, week 26, week 52]

Number of Treatment-emergent Adverse Events (TEAEs) [Time Frame: Weeks 0 - 57]

Change in HbA1c (Week 52) [Time Frame: Week 0, week 52]

Change in HDL Cholesterol (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/No) [Time Frame: Week 26 and week 52]

Change in Insulin Resistance (HOMA-IR) (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in Pulse Rate [Time Frame: Week 0, week 26, week 52]

Participants Who Achieved Weight Loss Above or Equal to 10% (Yes/No) [Time Frame: Week 26 and week 52]

Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes [Time Frame: Weeks 0 - 57]

Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol) ADA Target (Yes/no) [Time Frame: Week 26 and week 52]

Participants Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol), AACE Target (Yes/No) [Time Frame: Week 26 and week 52]

Anti-semaglutide Binding Antibody Levels [Time Frame: Weeks 0-57]

Change in Beta-cell Function (HOMA-B) (Ratio to Baseline) [Time Frame: Week 0, week 26 and week 52]

Change in SF-36: Mental Component Summary (MCS) [Time Frame: Week 0, week 26, week 52]

Change in Waist Circumference [Time Frame: Week 0, week 26 and week 52]

Semaglutide Plasma Concentration [Time Frame: Week 26 and week 52]

Time to Additional Anti-diabetic Medication [Time Frame: Weeks 0 - 52]

Secondary ID(s)

JapicCTI-173489

NN9924-4281

U1111-1181-4048

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03018028