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NCT01986855

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)

Completed Phase 3 Results posted Last updated 10 September 2018
What this trial tests

Phase 3 trial testing Ertugliflozin 5 mg in Type 2 Diabetes Mellitus in 468 participants. Completed in 28 September 2016.

Timeline
2 December 2013
Primary endpoint
28 September 2016
28 September 2016

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment468
Start date2 December 2013
Primary completion28 September 2016
Estimated completion28 September 2016

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

25 and older, any sex, with Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in A1C at Week 26 - Excluding Rescue Approach Primary · Baseline and Week 26

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.

GroupValue95% CI
Ertugliflozin 5 mg-0.29-0.44 – -0.14
Ertugliflozin 15 mg-0.41-0.56 – -0.27
Placebo-0.26-0.41 – -0.11
Percentage of Participants Who Experienced an Adverse Event (AE) Primary · Up to 54 weeks

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.

GroupValue95% CI
Ertugliflozin 5 mg84.8
Ertugliflozin 15 mg74.2
Placebo81.2
Percentage of Participants Who Discontinued Study Treatment Due to an AE Primary · Up to 52 weeks

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.

GroupValue95% CI
Ertugliflozin 5 mg8.2
Ertugliflozin 15 mg3.9
Placebo5.2
Change From Baseline in A1C at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach Secondary · Baseline and Week 26

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.

GroupValue95% CI
Ertugliflozin 5 mg-0.31-0.49 – -0.13
Ertugliflozin 15 mg-0.37-0.56 – -0.18
Placebo-0.28-0.47 – -0.08
Change From Baseline in Body Weight at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach Secondary · Baseline and Week 26

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.

GroupValue95% CI
Ertugliflozin 5 mg-1.31-1.86 – -0.76
Ertugliflozin 15 mg-1.39-1.97 – -0.81
Placebo0.46-0.13 – 1.04
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 Secondary · Baseline and Week 26

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.

GroupValue95% CI
Ertugliflozin 5 mg-2.33-4.98 – 0.33
Ertugliflozin 15 mg-4.36-7.11 – -1.62
Placebo-0.90-3.73 – 1.92
Change From Baseline in FPG at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach Secondary · Baseline and Week 26

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.

GroupValue95% CI
Ertugliflozin 5 mg-11.76-21.07 – -2.45
Ertugliflozin 15 mg-20.47-30.20 – -10.73
Placebo-4.95-15.03 – 5.13
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 Secondary · Week 26

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.

GroupValue95% CI
Ertugliflozin 5 mg16.2
Ertugliflozin 15 mg11.3
Placebo12.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 54 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 24/154 (16%)
Deaths:
Ertugliflozin 5 mg
Serious: 26/158 (16%)
Deaths:
Ertugliflozin 15 mg
Serious: 30/155 (19%)
Deaths:

Serious adverse events (83 terms)

ReactionSystemPlaceboErtugliflozin 5 mgErtugliflozin 15 mg
Angina pectorisCardiac disorders
Acute myocardial infarctionCardiac disorders
CellulitisInfections and infestations
Coronary artery diseaseCardiac disorders
Coronary artery stenosisCardiac disorders
Myocardial ischaemiaCardiac disorders
Abdominal painGastrointestinal disorders
Sudden deathGeneral disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
Ischaemic strokeNervous system disorders
Acute kidney injuryRenal and urinary disorders
Lymph node haemorrhageBlood and lymphatic system disorders
Angina unstableCardiac disorders
Atrial fibrillationCardiac disorders
BradycardiaCardiac disorders
Bundle branch block leftCardiac disorders
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
Cardiogenic shockCardiac disorders
Sinus node dysfunctionCardiac disorders
Retinal detachmentEye disorders
Cyclic vomiting syndromeGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
Peritoneal haemorrhageGastrointestinal disorders
Other adverse events (8 terms — click to expand)

ReactionSystemPlaceboErtugliflozin 5 mgErtugliflozin 15 mg
HypoglycaemiaMetabolism and nutrition disorders
Urinary tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
NasopharyngitisInfections and infestations
DizzinessNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
BronchitisInfections and infestations

Most-reported serious reactions: Angina pectoris, Acute myocardial infarction, Cellulitis, Coronary artery disease, Coronary artery stenosis, Myocardial ischaemia, Abdominal pain, Sudden death.

Data from ClinicalTrials.gov NCT01986855 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. SLC transporters as therapeutic targets: emerging opportunities.
    Lin L, Yee SW, Kim RB, Giacomini KM. · · 2015 · cited 653× · PMID 26111766 · DOI 10.1038/nrd4626
  2. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes.
    Nauck MA. · · 2014 · cited 227× · PMID 25246775 · DOI 10.2147/dddt.s50773
  3. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis.
    Li HL, Lip GYH, Feng Q, Fei Y, et al · · 2021 · cited 127× · PMID 33962654 · DOI 10.1186/s12933-021-01293-8
  4. Ertugliflozin in Patients with Stage 3 Chronic Kidney Disease and Type 2 Diabetes Mellitus: The VERTIS RENAL Randomized Study.
    Grunberger G, Camp S, Johnson J, Huyck S, et al · · 2018 · cited 114× · PMID 29159457 · DOI 10.1007/s13300-017-0337-5
  5. Sodium-Glucose Co-Transporter Inhibitors and Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
    Pandey AK, Okaj I, Kaur H, Belley-Cote EP, et al · · 2021 · cited 100× · PMID 34459238 · DOI 10.1161/jaha.121.022222
  6. The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus.
    Sahasrabudhe V, Terra SG, Hickman A, Saur D, et al · · 2017 · cited 36× · PMID 28703316 · DOI 10.1002/jcph.955
  7. Protective Effects of Sodium-Glucose Transporter 2 Inhibitors on Atrial Fibrillation and Atrial Flutter: A Systematic Review and Meta- Analysis of Randomized Placebo-Controlled Trials.
    Li D, Liu Y, Hidru TH, Yang X, et al · · 2021 · cited 34× · PMID 33815278 · DOI 10.3389/fendo.2021.619586
  8. Markers of Kidney Injury, Inflammation, and Fibrosis Associated With Ertugliflozin in Patients With CKD and Diabetes.
    Liu H, Sridhar VS, Lovblom LE, Lytvyn Y, et al · · 2021 · cited 32× · PMID 34386658 · DOI 10.1016/j.ekir.2021.05.022

Verify or expand the search:

Other trials of Ertugliflozin 5 mg

Trials testing the same drug.

Other recruiting trials for Type 2 Diabetes Mellitus

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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