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)

NCT01986855 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 8835-0012013-003587-31B1521016
• Study Type: interventional
• Target: 468
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline and Week 26

• 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.

  Up to 54 weeks

• 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.

  Up to 52 weeks

Secondary Outcomes (5)

• Change From Baseline in A1C at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach

  Baseline and Week 26

• Change From Baseline in Body Weight at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach

  Baseline and Week 26

• 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

  Baseline and Week 26

• Change From Baseline in FPG at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach

  Baseline and Week 26

• 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

  Week 26

Study Arms (3)

Ertugliflozin (5 mg)

EXPERIMENTAL

Ertugliflozin, 5 mg, oral, one 5 mg ertugliflozin tablet and one placebo tablet, once daily for 52 weeks

Drug: Ertugliflozin 5 mg; Drug: Placebo 10 mg

Ertugliflozin (15 mg)

EXPERIMENTAL

Ertugliflozin, 15 mg, oral, one 5 mg and one 10 mg tablet, once daily for 52 weeks

Drug: Ertugliflozin 10 mg

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo 5 mg; Drug: Placebo 10 mg

Interventions

Ertugliflozin 5 mg DRUG

Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks

Also known as: MK-8835, PF-04971729

Ertugliflozin (5 mg)

Placebo 5 mg DRUG

Placebo to ertugliflozin, oral, tablet, 5 mg tablet once daily for 52 weeks

Placebo

Ertugliflozin 10 mg DRUG

Ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks

Also known as: MK-8835, PF-04971729

Ertugliflozin (15 mg)

Placebo 10 mg DRUG

Placebo to ertugliflozin, oral, tablet, 10 mg tablet once daily for 52 weeks

Ertugliflozin (5 mg); Placebo

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Pfizer: collaborator

Related Publications (8)

• 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.

  PMID: 29159457 RESULT

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

• 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.

  PMID: 34213819 DERIVED

• 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.

  PMID: 32648108 DERIVED

• 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.

  PMID: 32372382 DERIVED

• 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.

  PMID: 32324082 DERIVED

• 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.

  PMID: 32324065 DERIVED

• 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.

  PMID: 31797522 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

After unblinding, analysis of retained plasma samples revealed unreported metformin use by \~17% of participants. Neither dose nor frequency of the protocol-prohibited metformin use is known. This potentially confounds glycemic analyses.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: November 19, 2013
• Study Start: December 2, 2013
• Primary Completion: September 28, 2016
• Study Completion: September 28, 2016
• Last Updated: September 10, 2018
• Results First Posted: October 4, 2017

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share