Back to resultsA Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ertugliflozin 5 mg
Placebo 5 mg
Ertugliflozin 10 mg
Placebo 10 mg
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Type 2 diabetes mellitus in accordance with American Diabetes Association guidelines
- Have Stage 3 chronic kidney disease
- On stable diabetes therapy (diet/exercise therapy alone or anti-hyperglycemic agents [AHA] monotherapy or combination therapy) for at least 6 weeks prior to study participation OR on metformin (with or without diet/exercise therapy or other AHA therapy) and is willing to undergo a 10-week metformin wash-off period
- Have an estimated glomerular filtration rate (eGFR) of ≥30 to <60 mL/min/1.73m^2
- Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2
- Male, postmenopausal female or surgically sterile female
- If a female of reproductive potential, agrees to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug.
Exclusion Criteria:
- History of type 1 diabetes mellitus or a history of ketoacidosis
- History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug - or chemical-induced, and post-organ transplant)
- History of nephrotic range proteinuria with hypoalbuminemia and edema
- History of rapidly progressive glomerulonephritis, lupus nephritis, renal or systemic vasculitis, renal artery stenosis with renovascular hypertension, or ischemic nephropathy
- History of familial renal glucosuria
- History of renal dialysis or renal transplant or renal disease requiring treatment with any immunosuppressive agent
- A known hypersensitivity or intolerance to any (sodium-glucose co-transporter 2) SGLT2 inhibitor
- On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable
- Has undergone bariatric surgery within the past 12 months
- Has been treated with rosiglitazone or other SGLT2 inhibitors within 12 weeks of study participation
- Has active, obstructive uropathy or indwelling urinary catheter
- History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation
- A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
- Known history of Human Immunodeficiency Virus (HIV)
- Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
- A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease
- Has any clinically significant malabsorption condition
- If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation
- Has been previously randomized in a study with ertugliflozin
- Has participated in other studies involving an investigational drug within 30 days prior or during study participation
- Has undergone a surgical procedure within 6 weeks prior to or during study participation
- Has a positive urine pregnancy test
- Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication
- Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication
- Excessive consumption of alcoholic beverages or binge drinking
- Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Ertugliflozin (5 mg)
Ertugliflozin (15 mg)
Placebo
Arm Description
Ertugliflozin, 5 mg, oral, one 5 mg ertugliflozin tablet and one placebo tablet, once daily for 52 weeks
Ertugliflozin, 15 mg, oral, one 5 mg and one 10 mg tablet, once daily for 52 weeks
Matching placebo
Outcomes
Primary Outcome Measures
Change From Baseline in A1C at Week 26 - Excluding Rescue Approach
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Secondary Outcome Measures
Change From Baseline in A1C at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Change From Baseline in Body Weight at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
This change from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
This change from baseline reflects the Week 26 sitting systolic blood pressure minus the Week 0 sitting systolic blood pressure. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Change From Baseline in FPG at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
This change from baseline reflects the Week 26 FPG minus the Week 0 FPG. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Percentage of Participants With A1C <7.0% (<53 mmol/Mol) at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Full Information
NCT ID
NCT01986855
First Posted
November 12, 2013
Last Updated
August 10, 2018
Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT01986855
Brief Title
A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)
Official Title
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Background Antihyperglycemic Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
December 2, 2013 (Actual)
Primary Completion Date
September 28, 2016 (Actual)
Study Completion Date
September 28, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
Collaborators
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The duration of this trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary objective of this trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared to the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
Detailed Description
Participants who meet protocol-defined glycemic rescue criteria will be permitted to have an adjustment in the dose(s) of background antihyperglycemic agent (AHA) therapy or addition of new AHA therapy as directed by their investigator until the participant no longer meets the rescue criteria.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
468 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ertugliflozin (5 mg)
Arm Type
Experimental
Arm Description
Ertugliflozin, 5 mg, oral, one 5 mg ertugliflozin tablet and one placebo tablet, once daily for 52 weeks
Arm Title
Ertugliflozin (15 mg)
Arm Type
Experimental
Arm Description
Ertugliflozin, 15 mg, oral, one 5 mg and one 10 mg tablet, once daily for 52 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin 5 mg
Other Intervention Name(s)
MK-8835, PF-04971729
Intervention Description
Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo 5 mg
Intervention Description
Placebo to ertugliflozin, oral, tablet, 5 mg tablet once daily for 52 weeks
Intervention Type
Drug
Intervention Name(s)
Ertugliflozin 10 mg
Other Intervention Name(s)
MK-8835, PF-04971729
Intervention Description
Ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo 10 mg
Intervention Description
Placebo to ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks
Primary Outcome Measure Information:
Title
Change From Baseline in A1C at Week 26 - Excluding Rescue Approach
Description
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Time Frame
Baseline and Week 26
Title
Percentage of Participants Who Experienced an Adverse Event (AE)
Description
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame
Up to 54 weeks
Title
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Description
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time Frame
Up to 52 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in A1C at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
Description
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Body Weight at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
Description
This change from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
Description
This change from baseline reflects the Week 26 sitting systolic blood pressure minus the Week 0 sitting systolic blood pressure. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Time Frame
Baseline and Week 26
Title
Change From Baseline in FPG at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
Description
This change from baseline reflects the Week 26 FPG minus the Week 0 FPG. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Time Frame
Baseline and Week 26
Title
Percentage of Participants With A1C <7.0% (<53 mmol/Mol) at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach
Description
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.
Time Frame
Week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Type 2 diabetes mellitus in accordance with American Diabetes Association guidelines
Have Stage 3 chronic kidney disease
On stable diabetes therapy (diet/exercise therapy alone or anti-hyperglycemic agents [AHA] monotherapy or combination therapy) for at least 6 weeks prior to study participation OR on metformin (with or without diet/exercise therapy or other AHA therapy) and is willing to undergo a 10-week metformin wash-off period
Have an estimated glomerular filtration rate (eGFR) of ≥30 to <60 mL/min/1.73m^2
Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2
Male, postmenopausal female or surgically sterile female
If a female of reproductive potential, agrees to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug.
Exclusion Criteria:
History of type 1 diabetes mellitus or a history of ketoacidosis
History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug - or chemical-induced, and post-organ transplant)
History of nephrotic range proteinuria with hypoalbuminemia and edema
History of rapidly progressive glomerulonephritis, lupus nephritis, renal or systemic vasculitis, renal artery stenosis with renovascular hypertension, or ischemic nephropathy
History of familial renal glucosuria
History of renal dialysis or renal transplant or renal disease requiring treatment with any immunosuppressive agent
A known hypersensitivity or intolerance to any (sodium-glucose co-transporter 2) SGLT2 inhibitor
On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable
Has undergone bariatric surgery within the past 12 months
Has been treated with rosiglitazone or other SGLT2 inhibitors within 12 weeks of study participation
Has active, obstructive uropathy or indwelling urinary catheter
History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation
A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
Known history of Human Immunodeficiency Virus (HIV)
Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease
Has any clinically significant malabsorption condition
If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation
Has been previously randomized in a study with ertugliflozin
Has participated in other studies involving an investigational drug within 30 days prior or during study participation
Has undergone a surgical procedure within 6 weeks prior to or during study participation
Has a positive urine pregnancy test
Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication
Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication
Excessive consumption of alcoholic beverages or binge drinking
Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
29159457
Citation
Grunberger G, Camp S, Johnson J, Huyck S, Terra SG, Mancuso JP, Jiang ZW, Golm G, Engel SS, Lauring B. Ertugliflozin in Patients with Stage 3 Chronic Kidney Disease and Type 2 Diabetes Mellitus: The VERTIS RENAL Randomized Study. Diabetes Ther. 2018 Feb;9(1):49-66. doi: 10.1007/s13300-017-0337-5. Epub 2017 Nov 20.
Results Reference
result
PubMed Identifier
34213819
Citation
Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
Results Reference
derived
PubMed Identifier
32648108
Citation
Gallo S, Calle RA, Terra SG, Pong A, Tarasenko L, Raji A. Effects of Ertugliflozin on Liver Enzymes in Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis of Phase 3 Trials. Diabetes Ther. 2020 Aug;11(8):1849-1860. doi: 10.1007/s13300-020-00867-1. Epub 2020 Jul 9.
Results Reference
derived
PubMed Identifier
32372382
Citation
Patel S, Hickman A, Frederich R, Johnson S, Huyck S, Mancuso JP, Gantz I, Terra SG. Safety of Ertugliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Seven Phase 3 Randomized Controlled Trials. Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.
Results Reference
derived
PubMed Identifier
32324082
Citation
Liu J, Tarasenko L, Pong A, Huyck S, Wu L, Patel S, Hickman A, Mancuso JP, Gantz I, Terra SG. Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Aug;36(8):1277-1284. doi: 10.1080/03007995.2020.1760228. Epub 2020 May 13.
Results Reference
derived
PubMed Identifier
32324065
Citation
Liu J, Tarasenko L, Pong A, Huyck S, Patel S, Hickman A, Mancuso JP, Ellison MC, Gantz I, Terra SG. Efficacy and safety of ertugliflozin in Hispanic/Latino patients with type 2 diabetes mellitus. Curr Med Res Opin. 2020 Jul;36(7):1097-1106. doi: 10.1080/03007995.2020.1760227. Epub 2020 May 13.
Results Reference
derived
PubMed Identifier
31797522
Citation
Liu J, Patel S, Cater NB, Wu L, Huyck S, Terra SG, Hickman A, Darekar A, Pong A, Gantz I. Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2020 Apr;22(4):574-582. doi: 10.1111/dom.13931. Epub 2020 Jan 3.
Results Reference
derived
Learn more about this trial
A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)
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