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A Study of Once-Daily NNC0090-2746 in Participants With Type 2 Diabetes Inadequately Controlled With Metformin

Primary Purpose

Diabetes, Diabetes Mellitus Type 2

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Liraglutide
Metformin
Placebo
NNC0090-2746
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants aged 18 to 70 years, inclusive
  • Active diagnosis of T2D for greater than or equal to (>/=) 3 months
  • For females of childbearing potential and males with female partners of childbearing potential, agreement to use highly effective contraceptive measures
  • Treated with a stable dose of metformin for at least 8 weeks prior to randomization, and expected to remain at the same stable dose throughout study participation
  • Hemoglobin A1c (HbA1c) >/= 7.2% and less than or equal to (</=) 10.5%
  • Fasting plasma glucose (FPG) less than (<) 250 milligrams per deciliter (mg/dL)
  • C-peptide greater than (>) 1.5 nanograms per milliliter (ng/mL)
  • Body mass index (BMI) >/= 27 kilograms per meter-squared (kg/m^2) and </= 44 kg/m^2
  • Stable weight (+/- 5%) within 12 weeks prior to Screening
  • Willing and able to maintain existing diet and exercise habits throughout the study
  • Capable of performing SC self-injections on a daily basis during the study

Exclusion Criteria:

  • Females who are pregnant or lactating
  • History of type 1 diabetes (T1D), diabetes resulting from pancreatic injury, or secondary forms of diabetes such as Cushing's Syndrome or acromegaly
  • History of acute metabolic complications such as diabetic ketoacidosis or state of hyperosmolar hyperglycemia
  • History of clinically significant diabetic complications such as diabetic proliferative retinopathy or severe diabetic neuropathy (requiring treatment with antidepressants or opioids)
  • History of severe hypoglycemia within 6 months prior to Screening
  • History of chronic gastrointestinal (GI) conditions that could impede gastric emptying or potentially affect the interpretation of the study data
  • History of weight loss surgery or weight loss procedure involving the GI tract, such as gastric bypass, gastric stapling, or gastric banding
  • History of an eating disorder (e.g., bulimia, anorexia)
  • History of malignancy (except treated basal or squamous cell skin cancer) within 5 years prior to Screening
  • Personal or family history of medullary thyroid carcinoma
  • History of multiple endocrine neoplasia syndrome type 2
  • History of chronic or acute pancreatitis or hemochromatosis
  • History of significant cardiovascular disease (such as congestive heart failure New York Heart Association Class II to IV, myocardial infarction within the previous 6 months, coronary disease, or uncontrolled hypertension)
  • History of clinically significant renal or liver disease
  • History of hypersensitivity or previous intolerance to incretin or glucagon analogues
  • Elevations in lipase or amylase levels at Screening > 1.5 times the upper limit of normal (ULN) and considered clinically significant by the investigator
  • Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAG), or hepatitis C antibody test at Screening
  • Receipt of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to Screening, or active enrollment in another investigational medication or device study
  • Any condition, disorder, or abnormal laboratory test findings at screening that, in the judgment of the investigator, would interfere with the participant's ability to comply with all study requirements, or would require the administration of a treatment during the study that could potentially affect the interpretation of the study data, or would place the participant at unacceptable risk by his/her participation in the study

Sites / Locations

  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Active Comparator

Arm Label

Treatment Period: Placebo QD

Treatment Period: NNC0090-2746 QD

Treatment Period: Liraglutide QD

Arm Description

Participants will receive daily SC placebo injections during the 12-week, double-blind treatment period.

Participants will receive daily 1.8-mg SC injections of NNC0090-2746 during the 12-week, double-blind treatment period.

Participants will receive open-label liraglutide via SC injection during the 12-week treatment period. The dose scheme will be as follows: 0.6 milligrams (mg) each day during Week 1, followed by 1.2 mg each day during Week 2, and 1.8 mg each day from Weeks 3 to 12.

Outcomes

Primary Outcome Measures

Change in HbA1c

Secondary Outcome Measures

Change in body weight
Percent change in body weight
Change in fasting plasma glucose (FPG)
Change in post-prandial plasma glucose level
Change in post-prandial insulin level
Change in post-prandial C-peptide level
Change in beta-cell function
According to the Homeostasis Model Assessment (HOMA) score
Incidence of treatment-emergent adverse events
Change in percent HbA1c

Full Information

First Posted
July 30, 2014
Last Updated
July 20, 2020
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT02205528
Brief Title
A Study of Once-Daily NNC0090-2746 in Participants With Type 2 Diabetes Inadequately Controlled With Metformin
Official Title
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Phase 2a Study With an Open-Label Active Group to Assess the Efficacy and Safety of Once-Daily NNC0090-2746 in Type 2 Diabetic Patients Inadequately Controlled With Metformin
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
August 18, 2014 (Actual)
Primary Completion Date
September 15, 2015 (Actual)
Study Completion Date
September 15, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

5. Study Description

Brief Summary
This trial is conducted in the United States of America (USA). The aim of the trial is to investigate the efficacy, safety, and tolerability of once-daily subcutaneous (SC) injections of NNC0090-2746 for 12 weeks, as an adjunct to metformin, in participants with T2D.

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 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
108 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Period: Placebo QD
Arm Type
Placebo Comparator
Arm Description
Participants will receive daily SC placebo injections during the 12-week, double-blind treatment period.
Arm Title
Treatment Period: NNC0090-2746 QD
Arm Type
Experimental
Arm Description
Participants will receive daily 1.8-mg SC injections of NNC0090-2746 during the 12-week, double-blind treatment period.
Arm Title
Treatment Period: Liraglutide QD
Arm Type
Active Comparator
Arm Description
Participants will receive open-label liraglutide via SC injection during the 12-week treatment period. The dose scheme will be as follows: 0.6 milligrams (mg) each day during Week 1, followed by 1.2 mg each day during Week 2, and 1.8 mg each day from Weeks 3 to 12.
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Intervention Description
Liraglutide will be self-administered daily via SC injection according to manufacturer specifications.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin hydrochloride immediate- or extended-release oral tablets will be supplied by the participant or investigational site as standard-of-care treatment beginning at least 8 weeks prior to randomization and throughout the 12-week treatment period. Metformin will also be continued during the 4-week follow-up. Dose selection will be based upon manufacturer specifications.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to NNC0090-2746 will be self-administered daily via SC injection.
Intervention Type
Drug
Intervention Name(s)
NNC0090-2746
Intervention Description
NNC0090-2746 solution will be self-administered in daily doses of 1.8 mg via SC injection.
Primary Outcome Measure Information:
Title
Change in HbA1c
Time Frame
Day 1; Week 8
Secondary Outcome Measure Information:
Title
Change in body weight
Time Frame
Day 1; Week 8; Week 12
Title
Percent change in body weight
Time Frame
Day 1; Week 8; Week 12
Title
Change in fasting plasma glucose (FPG)
Time Frame
Day 1; Week 12
Title
Change in post-prandial plasma glucose level
Time Frame
Day -7; Week 12
Title
Change in post-prandial insulin level
Time Frame
Day -7; Week 12
Title
Change in post-prandial C-peptide level
Time Frame
Day -7; Week 12
Title
Change in beta-cell function
Description
According to the Homeostasis Model Assessment (HOMA) score
Time Frame
Day 1; Week 12
Title
Incidence of treatment-emergent adverse events
Time Frame
Day 1; Week 18
Title
Change in percent HbA1c
Time Frame
Day 1; Week 12

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants aged 18 to 70 years, inclusive Active diagnosis of T2D for greater than or equal to (>/=) 3 months For females of childbearing potential and males with female partners of childbearing potential, agreement to use highly effective contraceptive measures Treated with a stable dose of metformin for at least 8 weeks prior to randomization, and expected to remain at the same stable dose throughout study participation Hemoglobin A1c (HbA1c) >/= 7.2% and less than or equal to (</=) 10.5% Fasting plasma glucose (FPG) less than (<) 250 milligrams per deciliter (mg/dL) C-peptide greater than (>) 1.5 nanograms per milliliter (ng/mL) Body mass index (BMI) >/= 27 kilograms per meter-squared (kg/m^2) and </= 44 kg/m^2 Stable weight (+/- 5%) within 12 weeks prior to Screening Willing and able to maintain existing diet and exercise habits throughout the study Capable of performing SC self-injections on a daily basis during the study Exclusion Criteria: Females who are pregnant or lactating History of type 1 diabetes (T1D), diabetes resulting from pancreatic injury, or secondary forms of diabetes such as Cushing's Syndrome or acromegaly History of acute metabolic complications such as diabetic ketoacidosis or state of hyperosmolar hyperglycemia History of clinically significant diabetic complications such as diabetic proliferative retinopathy or severe diabetic neuropathy (requiring treatment with antidepressants or opioids) History of severe hypoglycemia within 6 months prior to Screening History of chronic gastrointestinal (GI) conditions that could impede gastric emptying or potentially affect the interpretation of the study data History of weight loss surgery or weight loss procedure involving the GI tract, such as gastric bypass, gastric stapling, or gastric banding History of an eating disorder (e.g., bulimia, anorexia) History of malignancy (except treated basal or squamous cell skin cancer) within 5 years prior to Screening Personal or family history of medullary thyroid carcinoma History of multiple endocrine neoplasia syndrome type 2 History of chronic or acute pancreatitis or hemochromatosis History of significant cardiovascular disease (such as congestive heart failure New York Heart Association Class II to IV, myocardial infarction within the previous 6 months, coronary disease, or uncontrolled hypertension) History of clinically significant renal or liver disease History of hypersensitivity or previous intolerance to incretin or glucagon analogues Elevations in lipase or amylase levels at Screening > 1.5 times the upper limit of normal (ULN) and considered clinically significant by the investigator Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAG), or hepatitis C antibody test at Screening Receipt of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to Screening, or active enrollment in another investigational medication or device study Any condition, disorder, or abnormal laboratory test findings at screening that, in the judgment of the investigator, would interfere with the participant's ability to comply with all study requirements, or would require the administration of a treatment during the study that could potentially affect the interpretation of the study data, or would place the participant at unacceptable risk by his/her participation in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR,1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Chino
State/Province
California
ZIP/Postal Code
91710
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Hawaiian Gardens
State/Province
California
ZIP/Postal Code
90716
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
Spring Valley
State/Province
California
ZIP/Postal Code
91978
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Sanford
State/Province
Florida
ZIP/Postal Code
32771
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
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Oxon Hill
State/Province
Maryland
ZIP/Postal Code
20745
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45227
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97404
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78404
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Manassas
State/Province
Virginia
ZIP/Postal Code
20110
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28768173
Citation
Frias JP, Bastyr EJ 3rd, Vignati L, Tschop MH, Schmitt C, Owen K, Christensen RH, DiMarchi RD. The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes. Cell Metab. 2017 Aug 1;26(2):343-352.e2. doi: 10.1016/j.cmet.2017.07.011.
Results Reference
result

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A Study of Once-Daily NNC0090-2746 in Participants With Type 2 Diabetes Inadequately Controlled With Metformin

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