Multiple Dose Trial Examining Dose Range, Escalation and Efficacy of Oral Semaglutide in Subjects With Type 2 Diabetes

This trial is conducted globally. The aim of the trial is to examine the dose range, escalation and efficacy of oral semaglutide in subjects with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: semaglutide; Drug: semaglutide; Drug: oral placebo

• Study Type: Interventional
• Enrollment (Actual): 632
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Saint Stefan, Austria, 8511
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1130
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1030
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1010
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1060
    • Novo Nordisk Investigational Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Novo Nordisk Investigational Site
• Canada
  • New Brunswick
    • Bathurst, New Brunswick, Canada, E2A 4Z9
      • Novo Nordisk Investigational Site
    • Moncton, New Brunswick, Canada, E1G 1A7
      • Novo Nordisk Investigational Site
  • Ontario
    • Burlington, Ontario, Canada, L7R 1E2
      • Novo Nordisk Investigational Site
    • Stayner, Ontario, Canada, L0M 1S0
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M9W 4L6
      • Novo Nordisk Investigational Site
  • Quebec
    • Pointe-Claire, Quebec, Canada, H9R 3J1
      • Novo Nordisk Investigational Site
• Denmark
  • Aalborg, Denmark, 9100
    • Novo Nordisk Investigational Site
  • Esbjerg, Denmark, 6700
    • Novo Nordisk Investigational Site
  • Hellerup, Denmark, 2900
    • Novo Nordisk Investigational Site
  • Hillerød, Denmark, 3400
    • Novo Nordisk Investigational Site
  • Svendborg, Denmark, 5700
    • Novo Nordisk Investigational Site
  • Århus C, Denmark, 8000
    • Novo Nordisk Investigational Site
• Germany
  • Elsterwerda, Germany, 04910
    • Novo Nordisk Investigational Site
  • Falkensee, Germany, 14612
    • Novo Nordisk Investigational Site
  • Friedrichsthal, Germany, 66299
    • Novo Nordisk Investigational Site
  • Hamburg, Germany, 22607
    • Novo Nordisk Investigational Site
  • Münster, Germany, 48145
    • Novo Nordisk Investigational Site
  • Saint Ingbert-Oberwürzbach, Germany, 66386
    • Novo Nordisk Investigational Site
  • Speyer, Germany, 67346
    • Novo Nordisk Investigational Site
• Israel
  • Beer Sheva, Israel, 84101
    • Novo Nordisk Investigational Site
  • Haifa, Israel, 31096
    • Novo Nordisk Investigational Site
  • Herzliya, Israel, 46851
    • Novo Nordisk Investigational Site
  • Holon, Israel, 58100
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91120
    • Novo Nordisk Investigational Site
  • Kfar Saba, Israel, 44281
    • Novo Nordisk Investigational Site
  • Rishon Le Zion, Israel, 75650
    • Novo Nordisk Investigational Site
• Italy
  • Milano, Italy, 20132
    • Novo Nordisk Investigational Site
  • Padova, Italy, 35128
    • Novo Nordisk Investigational Site
  • Roma, Italy, 00161
    • Novo Nordisk Investigational Site
  • Roma, Italy, 00133
    • Novo Nordisk Investigational Site
  • Verona, Italy, 37126
    • Novo Nordisk Investigational Site
• Malaysia
  • Ipoh, Malaysia, 30450
    • Novo Nordisk Investigational Site
  • Kota Bharu, Malaysia, 15586
    • Novo Nordisk Investigational Site
  • Penang, Malaysia, 10450
    • Novo Nordisk Investigational Site
  • Seri Manjung, Malaysia, 32040
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Novo Nordisk Investigational Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1829
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 2090
      • Novo Nordisk Investigational Site
• Spain
  • Almería, Spain, 04001
    • Novo Nordisk Investigational Site
  • Sabadell, Spain, 08208
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41010
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41003
    • Novo Nordisk Investigational Site
  • Valencia, Spain, 46026
    • Novo Nordisk Investigational Site
• Sweden
  • Karlstad, Sweden, 651 85
    • Novo Nordisk Investigational Site
  • Linköping, Sweden, 582 16
    • Novo Nordisk Investigational Site
  • Oskarshamn, Sweden, 572 28
    • Novo Nordisk Investigational Site
  • Örebro, Sweden, 701 85
    • Novo Nordisk Investigational Site
• United Kingdom
  • Belfast, United Kingdom, BT16 1RH
    • Novo Nordisk Investigational Site
  • Bexhill-on-Sea, United Kingdom, TN39 4SP
    • Novo Nordisk Investigational Site
  • Chester, United Kingdom, CH2 1UL
    • Novo Nordisk Investigational Site
  • Chesterfield, Derbyshire, United Kingdom, S40 4AA
    • Novo Nordisk Investigational Site
  • Crewe, United Kingdom, CW5 5NX
    • Novo Nordisk Investigational Site
  • Hinckley, United Kingdom, LE10 2SE
    • Novo Nordisk Investigational Site
  • Leicester, United Kingdom, LE5 4PW
    • Novo Nordisk Investigational Site
  • London, United Kingdom, W6 7HY
    • Novo Nordisk Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Novo Nordisk Investigational Site
  • California
    • Chula Vista, California, United States, 91911
      • Novo Nordisk Investigational Site
    • Long Beach, California, United States, 90806
      • Novo Nordisk Investigational Site
    • Poway, California, United States, 92064
      • Novo Nordisk Investigational Site
    • Santa Ana, California, United States, 92705
      • Novo Nordisk Investigational Site
    • Spring Valley, California, United States, 91978
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80904
      • Novo Nordisk Investigational Site
    • Denver, Colorado, United States, 80220
      • Novo Nordisk Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33014
      • Novo Nordisk Investigational Site
    • Plantation, Florida, United States, 33324
      • Novo Nordisk Investigational Site
    • South Miami, Florida, United States, 33143
      • Novo Nordisk Investigational Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Novo Nordisk Investigational Site
    • Conyers, Georgia, United States, 30094-5965
      • Novo Nordisk Investigational Site
  • Illinois
    • Addison, Illinois, United States, 60101
      • Novo Nordisk Investigational Site
    • Chicago, Illinois, United States, 60634
      • Novo Nordisk Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Novo Nordisk Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Novo Nordisk Investigational Site
    • Las Vegas, Nevada, United States, 89109
      • Novo Nordisk Investigational Site
  • New York
    • New York, New York, United States, 10001
      • Novo Nordisk Investigational Site
    • New York, New York, United States, 10032
      • Novo Nordisk Investigational Site
    • Rochester, New York, United States, 14609
      • Novo Nordisk Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Novo Nordisk Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Novo Nordisk Investigational Site
    • Salisbury, North Carolina, United States, 28144
      • Novo Nordisk Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Jersey Shore, Pennsylvania, United States, 17740
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19147
      • Novo Nordisk Investigational Site
  • South Carolina
    • Moncks Corner, South Carolina, United States, 29461
      • Novo Nordisk Investigational Site
  • Tennessee
    • Humboldt, Tennessee, United States, 38343
      • Novo Nordisk Investigational Site
    • Spring Hill, Tennessee, United States, 37174
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78209
      • Novo Nordisk Investigational Site
    • Sugar Land, Texas, United States, 77478
      • Novo Nordisk Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Novo Nordisk Investigational Site
  • Washington
    • Wenatchee, Washington, United States, 98801-2028
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI above or equal to 25 and below or equal to 40 kg/m^2
• Subjects diagnosed with T2D (Type 2 diabetes) treated with diet and exercise and/or who have been on a stable dose of metformin for at least 30 days prior to screening
• HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive)

Exclusion Criteria:

• Subjects on selected oral medication with a narrow therapeutic window, such as warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline and anticonvulsants
• History of chronic pancreatitis or idiopathic acute pancreatitis
• Chronic malabsorption, regardless of aetiology
• History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease
• Treatment with glucose lowering agent(s) other than metformin as stated in the inclusion criteria in a period of 90 days before the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1:Semaglutide tablets : 2.5 mg; 2.5 mg for 26 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Experimental: 2:Semaglutide tablets: 2.5 mg/5 mg; 2.5 mg for 4 weeks, then 5.0 mg for 22 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Experimental: 3:Semaglutide tablets: 5.0 mg/10 mg; 5.0 mg for 4 weeks, then 10 mg for 22 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Experimental: 4:Semaglutide tablets:5.0 mg/10 mg/20 mg; 5.0 mg for 4 weeks, then 10 mg for 4 weeks, then 20 mg for 18 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Experimental: 5:Semaglutide tablets:5.0 mg/10 mg/20 mg/40 mg; 5.0 mg for 4 weeks, then 10 mg for 4 weeks, then 20 mg for 4 weeks, then 40 mg for 14 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Experimental: 6:Semaglutide tablets:5.0 mg/10 mg/20 mg/40 mg; 5.0 mg for 8 weeks, then 10 mg for 8 weeks, then 20 mg for 8 weeks, then 40 mg for 2 weeks All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Experimental: 7:Semaglutide tablets: 5.0 mg/10 mg/20 mg/40 mg; 5.0 mg for 2 weeks, then 10 mg for 2 weeks, then 20 mg for 2 weeks, then 40 mg for 20 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen
Placebo Comparator: 8:Placebo tablets; All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: oral placebo; Once-daily oral administration as tablets.
Active Comparator: 9:Semaglutide injections :0.25 mg/0.50 mg/1.0 mg; 0.25 mg for 4 weeks, then 0.50 mg for 4 weeks, then 1.0 mg for 18 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone.	Drug: semaglutide; Once-daily oral administration as tablets.; Drug: semaglutide; Once-weekly,injected s.c./subcutaneously (under the skin) using a pen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin)	Change from baseline (week 0) in HbA1c was evaluated at week 26. The endpoint was evaluated 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.	Week 0, week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol)	Participants who achieved HbA1c <7.0%, was evaluated at week 26. The endpoint was evaluated 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.	After 26 weeks of treatment
Change in Body Weight	Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated 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.	Week 0, Week 26
Change in Waist Circumference	Change from baseline (week 0) in waist circumference was evaluated at week 26. The endpoint was evaluated 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.	Week 0, week 26
Change in Body Mass Index (BMI)	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. The endpoint was evaluated 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.	Week 0, week 26
Number of Treatment Emergent Adverse Events (TEAEs) Recorded	TEAEs were recorded during weeks 0-31 (26 weeks treatment period+5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Weeks 0-31
Number of Confirmed Hypoglycaemic Episodes Recorded	Treatment-emergent confirmed hypoglycaemic episodes were recorded during weeks 0-31 (26 weeks treatment period + 5 weeks 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. Confirmed hypoglycaemic episode is an episode that is severe according to the American Diabetes Association (ADA) classification or plasma glucose value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia.	Weeks 0-31

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2017 Oct 17;318(15):1460-1470. doi: 10.1001/jama.2017.14752.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2013
• Primary Completion (Actual): December 11, 2014
• Study Completion (Actual): December 11, 2014

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: August 13, 2013
• First Posted (Estimate): August 15, 2013

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 14, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NN9924-3790; 2012-004994-16 (EudraCT Number); U1111-1136-4716 (Other Identifier: WHO)