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Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin (PIONEER 8)

Primary Purpose

Diabetes, Diabetes Mellitus, Type 2

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

semaglutide

placebo

About this trial

This is an interventional treatment trial for Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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. - Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age above or equal to 20 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus 90 days or more prior to the day of screening. - HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive). - Stable treatment with one of the following insulin regimens (minimum 10 IU/day) 90 or more days prior to the day of screening. Maximum 20% change in total daily dose is acceptable: (1) Basal insulin alone or (2) Basal and bolus insulin in any combination or (3) Premixed insulin including combinations of soluble insulins 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 measure as required by local regulation or practice). For Greece only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence. For Japan only: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives. For Canada only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence - 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 (MI), stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation. - 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 defined as estimated Glomerular Filtration Rate (eGFR) less than 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term change of insulin treatment for acute illness for a total of 14 days or less. - Known hypoglycaemic unawareness according to Clarke's questionnaire. - 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 carcinoma in situ). - Subjects with alanine aminotransferase (ALT) more than 2.5 x upper normal limit (UNL).

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Semaglutide 3 mg

Semaglutide 3 mg + 7 mg

Semaglutide 3 mg + 7 mg + 14 mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change in HbA1c (Week 26)

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any.

Secondary Outcome Measures

Change in Body Weight (Week 26)

Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also evaluated based on data from the on-treatment without rescue medication observation period. It started at the date of first dose of trial product and excluded the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in HbA1c (Week 52)

Change from baseline (week 0) in HbA1c to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Body Weight (kg) (Week 52)

Change from baseline (week 0) in body weight to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Fasting Plasma Glucose (FPG)

Change from baseline (week 0) in FPG to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile

Change from baseline (week 0) in self-measured plasma glucose (SMPG) mean 7-point profile to week 26 and week 52. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in SMPG Mean Postprandial Increment Over All Meals

Change from baseline (week 0) in SMPG mean postprandial increment over all meals to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Body Weight (Percentage)

Relative change from baseline (week 0) in body weight (%) was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Body Mass Index

Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26 and 52. BMI was calculated based on body weight and height based on the formula: BMI kg/m^2 = body weight (kg)/(Height (m) x Height (m)). Data based on in-trial observation period is presented. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Waist Circumference

Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Total Cholesterol - Ratio to Baseline

Change from baseline in total cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in LDL Cholesterol - Ratio to Baseline

Change from baseline in LDL cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in HDL Cholesterol - Ratio to Baseline

Change from baseline (week 0) in HDL cholesterol (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Triglycerides - Ratio to Baseline

Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in Total Daily Insulin Dose

Change from baseline in total daily insulin dose to week 26 and week 52 is presented. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Participants Who Achieve: HbA1c < 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)

Number of particpants achieving HbA1c < 7.0 % (53 mmol/mol) according to American Diabetes Association (ADA) target, at week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Participants Who Achieve: HbA1c ≤ 6.5% (48 mmol/Mol) (AACE Target) (Yes/no)

Number of participants achieving HbA1c ≤ 6.5% (48 mmol/mol) according to American Association of Clinical Endocrinologists (AACE) target, at week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Participants Who Achieve Body Weight Loss ≥5% (Yes/no)

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Participants Who Achieve Body Weight Loss ≥10% (Yes/no)

Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiatiion of of rescue medication and/or premature trial product discontinuation, if any.

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26 and 52 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time to Additional Anti-diabetic Medication

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication was defined as use of new anti-diabetic medication for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time to Rescue Medication

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication was defined as use of new anti-diabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 1) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Change in Amylase - Ratio to Baseline

Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Lipase - Ratio to Baseline

Change from baseline (week 0) in lipase (units/litre (U/L)) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication

Change in Pulse Rate

Change from baseline (week 0) in pulse rate was evaluated at weeks 26 and 52 Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in SBP and DBP

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26 and 52 Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in ECG Evaluation

Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26 and 52. Change from baseline results are presented as shift in findings (normal; abnormal and not clinically significant (NCS); abnormal and clinically significant (CS)) from week 0 to week 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Physical Examination

Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2) and weeks 52 presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.

Change in Eye Examination Category

Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Semaglutide Plasma Concentrations for Population PK Analyses

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations were measured at week 4, 14, 26, 38 and 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26 and week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction.

Full Information

NCT ID

NCT03021187

First Posted

January 12, 2017

Last Updated

February 14, 2020

Sponsor

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT03021187

Brief Title

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin

Acronym

PIONEER 8

Official Title

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin. A 52-week, Randomised, Double-blind, Placebo-controlled Trial (PIONEER 8 - Insulin add-on)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

February 2, 2017 (Actual)

Primary Completion Date

January 18, 2018 (Actual)

Study Completion Date

August 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This trial is conducted globally. The aim of the trial is to investigate the efficacy and safety of oral semaglutide versus placebo in subjects with Type 2 Diabetes Mellitus treated with insulin. All subjects should continue their pre-trial insulin therapy (basal, basal-bolus or premixed regimen including combinations of soluble insulins) throughout the trial. Subjects treated with metformin in addition to insulin treatment must continue their metformin treatment throughout the entire trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes, Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

731 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Semaglutide 3 mg

Arm Type

Experimental

Arm Title

Semaglutide 3 mg + 7 mg

Arm Type

Experimental

Arm Title

Semaglutide 3 mg + 7 mg + 14 mg

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

semaglutide

Intervention Description

Oral semaglutide administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment

Intervention Type

Drug

Intervention Name(s)

semaglutide

Intervention Description

Oral semaglutide (3 mg followed by 7 mg) administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment

Intervention Type

Drug

Intervention Name(s)

semaglutide

Intervention Description

Oral semaglutide (3 mg followed by 7 mg and finally 14 mg) administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Oral semaglutide placebo administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment

Primary Outcome Measure Information:

Title

Change in HbA1c (Week 26)

Description

Time Frame

Week 0, week 26

Secondary Outcome Measure Information:

Title

Change in Body Weight (Week 26)

Description

Time Frame

Week 0, week 26

Title

Change in HbA1c (Week 52)

Description

Time Frame

Week 0, week 52

Title

Change in Body Weight (kg) (Week 52)

Description

Time Frame

Week 0, week 52

Title

Change in Fasting Plasma Glucose (FPG)

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile

Description

Time Frame

Week 0, week 26, week 52

Title

Change in SMPG Mean Postprandial Increment Over All Meals

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Body Weight (Percentage)

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Body Mass Index

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Waist Circumference

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Total Cholesterol - Ratio to Baseline

Description

Time Frame

Week 0, week 26, week 52

Title

Change in LDL Cholesterol - Ratio to Baseline

Description

Time Frame

Week 0, week 26, week 52

Title

Change in HDL Cholesterol - Ratio to Baseline

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Triglycerides - Ratio to Baseline

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Total Daily Insulin Dose

Description

Time Frame

Week 0, week 26, week 52

Title

Participants Who Achieve: HbA1c < 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)

Description

Time Frame

Week 26, week 52

Title

Participants Who Achieve: HbA1c ≤ 6.5% (48 mmol/Mol) (AACE Target) (Yes/no)

Description

Time Frame

Week 26, week 52

Title

Participants Who Achieve Body Weight Loss ≥5% (Yes/no)

Description

Time Frame

Week 26, week 52

Title

Participants Who Achieve Body Weight Loss ≥10% (Yes/no)

Description

Time Frame

Week 26, week 52

Title

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Description

Time Frame

Week 26, week 52

Title

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Description

Time Frame

Week 26, week 52

Title

Time to Additional Anti-diabetic Medication

Description

Time Frame

Weeks 0-52

Title

Time to Rescue Medication

Description

Time Frame

Weeks 0-52

Title

Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product

Description

Time Frame

Weeks 0-57

Title

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Description

Time Frame

Weeks 0-57

Title

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Description

Time Frame

Weeks 0-57

Title

Change in Amylase - Ratio to Baseline

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Lipase - Ratio to Baseline

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Pulse Rate

Description

Time Frame

Week 0, week 26, week 52

Title

Change in SBP and DBP

Description

Time Frame

Week 0, week 26, week 52

Title

Change in ECG Evaluation

Description

Time Frame

Week 0, week 26, week 52

Title

Change in Physical Examination

Description

Time Frame

Week -2, week 52

Title

Change in Eye Examination Category

Description

Time Frame

Week -2, week 52

Title

Semaglutide Plasma Concentrations for Population PK Analyses

Description

Time Frame

Weeks 0-52

Title

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

Description

Time Frame

Week 0, week 26, week 52

Title

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

Description

Time Frame

Week 0, week 26, week 52

Title

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

Description

Time Frame

Week 0, week 26, week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Facility Information:

Facility Name

Novo Nordisk Investigational Site

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36207

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35211

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Fountain Hills

State/Province

Arizona

ZIP/Postal Code

85268

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Glendale

State/Province

Arizona

ZIP/Postal Code

85308

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Mesa

State/Province

Arizona

ZIP/Postal Code

85213

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85037

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85723-0001

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85741

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Anaheim

State/Province

California

ZIP/Postal Code

92801

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Fresno

State/Province

California

ZIP/Postal Code

93720

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90017

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90057

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Riverside

State/Province

California

ZIP/Postal Code

92506

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Van Nuys

State/Province

California

ZIP/Postal Code

91405

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Vista

State/Province

California

ZIP/Postal Code

92083

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80904

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80246

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33016

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60607

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Franklin

State/Province

Indiana

ZIP/Postal Code

46131

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40503

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Paducah

State/Province

Kentucky

ZIP/Postal Code

42003

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70002

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Natchitoches

State/Province

Louisiana

ZIP/Postal Code

71457-5881

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Hyattsville

State/Province

Maryland

ZIP/Postal Code

20782

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Rockville

State/Province

Maryland

ZIP/Postal Code

20852

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Troy

State/Province

Michigan

ZIP/Postal Code

48098

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Henderson

State/Province

Nevada

ZIP/Postal Code

89052-2649

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89148

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

West Seneca

State/Province

New York

ZIP/Postal Code

14224

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Asheville

State/Province

North Carolina

ZIP/Postal Code

28803

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27517

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45245

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45439

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Beaver

State/Province

Pennsylvania

ZIP/Postal Code

15009

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Lansdale

State/Province

Pennsylvania

ZIP/Postal Code

19446-1002

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Summerville

State/Province

South Carolina

ZIP/Postal Code

29485

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37411

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Kingsport

State/Province

Tennessee

ZIP/Postal Code

37660-4652

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Austin

State/Province

Texas

ZIP/Postal Code

78731

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75251

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-9302

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77090

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Mesquite

State/Province

Texas

ZIP/Postal Code

75149

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Midland

State/Province

Texas

ZIP/Postal Code

79707

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Round Rock

State/Province

Texas

ZIP/Postal Code

78681

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Murray

State/Province

Utah

ZIP/Postal Code

84123

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Winchester

State/Province

Virginia

ZIP/Postal Code

22601

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3E 3P4

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

Moncton

State/Province

New Brunswick

ZIP/Postal Code

E1G 1A7

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

Brampton

State/Province

Ontario

ZIP/Postal Code

L6S 0C6

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

Etobicoke

State/Province

Ontario

ZIP/Postal Code

M9W 1P1

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

London

State/Province

Ontario

ZIP/Postal Code

N6G 2M1

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T 3L9

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

Waterloo

State/Province

Ontario

ZIP/Postal Code

N2J 1C4

Country

Canada

Facility Name

Novo Nordisk Investigational Site

City

Besançon cedex

ZIP/Postal Code

25030

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Bourgoin-jallieu

ZIP/Postal Code

38302

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Brest

ZIP/Postal Code

29200

Country

France

Facility Name

Novo Nordisk Investigational Site

City

LA ROCHE-sur-YON cedex 9

ZIP/Postal Code

85295

Country

France

Facility Name

Novo Nordisk Investigational Site

City

LA ROCHELLE cedex

ZIP/Postal Code

17019

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Le Coudray

ZIP/Postal Code

28630

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Le Creusot

ZIP/Postal Code

71200

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Narbonne

ZIP/Postal Code

11108

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Paris

ZIP/Postal Code

75014

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Saint Herblain

ZIP/Postal Code

44800

Country

France

Facility Name

Novo Nordisk Investigational Site

City

TOULOUSE cedex

ZIP/Postal Code

31054

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Venissieux

ZIP/Postal Code

69200

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Athens

ZIP/Postal Code

GR-11527

Country

Greece

Facility Name

Novo Nordisk Investigational Site

City

Athens

ZIP/Postal Code

GR-17562

Country

Greece

Facility Name

Novo Nordisk Investigational Site

City

Ioannina

ZIP/Postal Code

45500

Country

Greece

Facility Name

Novo Nordisk Investigational Site

City

Larissa

ZIP/Postal Code

GR-41110

Country

Greece

Facility Name

Novo Nordisk Investigational Site

City

Piraeus

ZIP/Postal Code

GR-18536

Country

Greece

Facility Name

Novo Nordisk Investigational Site

City

Thessaloniki

ZIP/Postal Code

GR-54649

Country

Greece

Facility Name

Novo Nordisk Investigational Site

City

Ahmedabad

State/Province

Gujarat

ZIP/Postal Code

380007

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Bangalore

State/Province

Karnataka

ZIP/Postal Code

560 017

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Kozhikode

State/Province

Kerala

ZIP/Postal Code

673017

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Indore

State/Province

Madhya Pradesh

ZIP/Postal Code

452010

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Mumbai

State/Province

Maharashtra

ZIP/Postal Code

400008

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Mumbai

State/Province

Maharashtra

ZIP/Postal Code

400010

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Pune

State/Province

Maharashtra

ZIP/Postal Code

411001

Country

India

Facility Name

Novo Nordisk Investigational Site

City

New Dehli

State/Province

New Delhi

ZIP/Postal Code

110029

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Jaipur

State/Province

Rajasthan

ZIP/Postal Code

302004

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Chennai

State/Province

Tamil Nadu

ZIP/Postal Code

600086

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Kolkata

State/Province

West Bengal

ZIP/Postal Code

700054

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Kolkata

ZIP/Postal Code

700020

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Amagasaki-shi, Hyogo

ZIP/Postal Code

661-0002

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Chuo-ku, Tokyo

ZIP/Postal Code

103-0002

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Ebina-shi, Kanagawa

ZIP/Postal Code

243-0432

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Iruma-shi, Saitama

ZIP/Postal Code

358-0011

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kanagawa

ZIP/Postal Code

247-0055

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kumamoto-shi, Kumamoto

ZIP/Postal Code

860-0811

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kumamoto

ZIP/Postal Code

862-0976

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Miyazaki

ZIP/Postal Code

880-0034

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Naka-shi

ZIP/Postal Code

311 0113

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Osaka

ZIP/Postal Code

569-1045

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Saga-shi, Saga

ZIP/Postal Code

849-0937

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Sapporo-shi

ZIP/Postal Code

062 0007

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Shimotsuke-shi, Tochigi

ZIP/Postal Code

329-0433

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Shizuoka-shi, Shizuoka

ZIP/Postal Code

424-0853

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Suita-shi, Osaka

ZIP/Postal Code

565-0853

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Tokyo

ZIP/Postal Code

103-0027

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Tokyo

ZIP/Postal Code

103-0028

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Tokyo

ZIP/Postal Code

105-8471

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Ube-shi, Yamaguchi

ZIP/Postal Code

755-0046

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Durango

ZIP/Postal Code

34000

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

San Luis Potosi

ZIP/Postal Code

78200

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Bialystok

ZIP/Postal Code

15-404

Country

Poland

Facility Name

Novo Nordisk Investigational Site

City

Lublin

ZIP/Postal Code

20-044

Country

Poland

Facility Name

Novo Nordisk Investigational Site

City

Poznan

ZIP/Postal Code

60-589

Country

Poland

Facility Name

Novo Nordisk Investigational Site

City

Pulawy

ZIP/Postal Code

24-100

Country

Poland

Facility Name

Novo Nordisk Investigational Site

City

Manati

ZIP/Postal Code

00674

Country

Puerto Rico

Facility Name

Novo Nordisk Investigational Site

City

Kazan

ZIP/Postal Code

420073

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Penza

ZIP/Postal Code

440026

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Saint-Petersburg

ZIP/Postal Code

191119

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Saint-Petersburg

ZIP/Postal Code

194354

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

St. Petersburg

ZIP/Postal Code

194354

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Citations:

PubMed Identifier

31530667

Citation

Zinman B, Aroda VR, Buse JB, Cariou B, Harris SB, Hoff ST, Pedersen KB, Tarp-Johansen MJ, Araki E; PIONEER 8 Investigators. Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Diabetes Care. 2019 Dec;42(12):2262-2271. doi: 10.2337/dc19-0898. Epub 2019 Sep 17.

Results Reference

result

PubMed Identifier

33660198

Citation

Pratley RE, Crowley MJ, Gislum M, Hertz CL, Jensen TB, Khunti K, Mosenzon O, Buse JB. Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Diabetes Ther. 2021 Apr;12(4):1099-1116. doi: 10.1007/s13300-020-00994-9. Epub 2021 Mar 4.

Results Reference

derived

PubMed Identifier

32998732

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.

Results Reference

derived

PubMed Identifier

32267058

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.

Results Reference

derived

PubMed Identifier

31903692

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.

Results Reference

derived

Learn more about this trial

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin

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Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin (PIONEER 8)

Diabetes, Diabetes Mellitus, Type 2

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial