A Study of the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise (MK-8835-003, VERTIS MONO)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01958671
Collaborator
Pfizer (Industry)
461
3
33.6
Study Details
Study Description
Brief Summary
This trial will evaluate the efficacy and safety of ertugliflozin monotherapy in the treatment of participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on diet and exercise. This trial consists of a run-in period of 3 to 11 weeks, a 26-week placebo-controlled treatment period (Phase A), and a 26-week active treatment period (Phase B). The primary hypotheses of the trial are that at Week 26, the mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo and the mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
461 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-blind, Placebo-controlled, 26-week Multicenter Study With a 26-Week Extension to Evaluate the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise
Actual Study Start Date
:
Oct 9, 2013
Actual Primary Completion Date
:
Jul 28, 2016
Actual Study Completion Date
:
Jul 28, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ertugliflozin 5 mg/Ertugliflozin 5 mg Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
Drug: Ertugliflozin 5 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
Drug: Placebo to Ertugliflozin
One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening for 2 weeks and 1000 mg (2 tablets 500 mg) in the morning and 1000 mg (2 tablets 500 mg) in the evening, thereafter.
Other Names:
Drug: Placebo to Metformin
1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter.
Drug: Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.
|
| Experimental: Ertugliflozin 15 mg/Ertugliflozin 15 mg Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
Drug: Ertugliflozin 5 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
Drug: Ertugliflozin 10 mg
One tablet taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Other Names:
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening for 2 weeks and 1000 mg (2 tablets 500 mg) in the morning and 1000 mg (2 tablets 500 mg) in the evening, thereafter.
Other Names:
Drug: Placebo to Metformin
1 tablet in the morning and 1 tablet in the evening for 2 weeks, 2 tablets in the morning and 1 tablet in the evening for 2 weeks and 2 tablets in the morning and 2 tablets in the evening, thereafter.
Drug: Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.
|
| Other: Placebo/Metformin Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
Drug: Placebo to Ertugliflozin
One placebo tablet matching the ertugliflozin 5 mg tablet and/or 1 placebo tablet matching the ertugliflozin 10 mg tablet per day taken orally the same time in the morning from Day 1 through Week 52 (Phase A and Phase B).
Drug: Metformin
500 mg (1 tablet) in the morning and 500 mg (1 tablet) in the evening for 2 weeks, 1000 mg (2 tablets 500 mg) in the morning and 500 mg (1 tablet) in the evening for 2 weeks and 1000 mg (2 tablets 500 mg) in the morning and 1000 mg (2 tablets 500 mg) in the evening, thereafter.
Other Names:
Drug: Glimepiride
Dosing and titration of glimepiride as rescue therapy was determined by the investigator.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline In A1C at Week 26 [Baseline and Week 26]
A1C is measured as percent. The change from baseline is the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
- Percentage of Participants Experiencing An Adverse Event (AE) [Up to 54 weeks (including 2 weeks following last dose)]
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
- Percentage of Participants Discontinuing Study Treatment Due to an AE [Up to 52 weeks]
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
Secondary Outcome Measures
- Change From Baseline in FPG at Week 26 [Baseline and Week 26]
The change from baseline is the Week 26 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of glycemic rescue therapy.
- Change From Baseline in Body Weight at Week 26 [Baseline and Week 26]
The change from baseline is the Week 26 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy.
- Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26 [Week 26]
A1C is measured as percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
- Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level [Baseline]
Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the Mixed Meal Tolerance Test (MMTT). Change from baseline in 2-hr PPG level at Week 26 data are presented in the following outcome measure.
- Change From Baseline in 2-hr PPG at Week 26 [Baseline and Week 26]
The change from baseline is the Week 26 2-hr PPG minus the Week 0 2-hr PPG. Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the MMTT. Data presented exclude data following the initiation of rescue therapy.
- Baseline Sitting Systolic Blood Pressure (SBP) [Baseline]
Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in SBP at Week 26 data are presented in the following outcome measure.
- Change From Baseline in SBP at Week 26 [Baseline and Week 26]
The change from baseline is the Week 26 SBP minus the Week 0 SBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.
- Baseline Sitting Diastolic Blood Pressure (DBP) [Baseline]
Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in DBP at Week 26 data are presented in the following outcome measure.
- Change From Baseline in DBP at Week 26 [Baseline and Week 26]
The change from baseline is the Week 26 DBP minus the Week 0 DBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of T2DM in accordance to American Diabetes Association guidelines
-
Participants with no prior allowable oral anti-hyperglycemic agents (AHA) for at least 8 weeks prior to study participation or participants on a single allowable oral AHA at the start of study participation
-
Participants on a single allowable AHA must be willing to discontinue this medication at the Screening Visit (S2) and remain off this medication for the duration of the trial. Allowable oral AHAs for discontinuation are metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides or alpha-glucosidase inhibitors.
Exclusion Criteria:
-
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 clinically significant electrocardiogram abnormality
-
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
-
A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor or metformin
-
On a blood pressure or lipid altering medication that have not been on a stable dose for at least 4 weeks prior to study participation
-
A surgical procedure within 4 weeks prior to study participation or planned major surgery during the trial
-
Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
-
Pregnant or breast-feeding, or is expecting to conceive during the trial, including 14 days following the last dose of study drug
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
- Pfizer
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01958671
Other Study ID Numbers:
- 8835-003
- 2013-002519-90
- B1521022
First Posted:
Oct 9, 2013
Last Update Posted:
Sep 29, 2017
Last Verified:
Jul 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin |
|---|---|---|---|
| Arm/Group Description | Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
| Period Title: Overall Study | |||
| STARTED | 156 | 152 | 153 |
| COMPLETED | 137 | 128 | 121 |
| NOT COMPLETED | 19 | 24 | 32 |
Baseline Characteristics
| Arm/Group Title | Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin | Total |
|---|---|---|---|---|
| Arm/Group Description | Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Total of all reporting groups |
| Overall Participants | 156 | 152 | 153 | 461 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
56.8
(11.4)
|
56.2
(10.8)
|
56.1
(10.9)
|
56.4
(11.0)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
67
42.9%
|
62
40.8%
|
71
46.4%
|
200
43.4%
|
| Male |
89
57.1%
|
90
59.2%
|
82
53.6%
|
261
56.6%
|
| Hemoglobin A1c (A1C) (Percent) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Percent] |
8.16
(0.88)
|
8.35
(1.12)
|
8.11
(0.92)
|
8.21
(0.98)
|
| Fasting plasma glucose (FPG) (mg/dL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mg/dL] |
180.9
(48.5)
|
179.1
(48.2)
|
180.2
(45.8)
|
180.1
(47.4)
|
| Estimated glomerular filtration rate (eGFR) (mL/min/1.75m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [mL/min/1.75m^2] |
88.5
(18.4)
|
88.3
(18.0)
|
86.2
(19.4)
|
87.7
(18.6)
|
| Body weight (Kilograms) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Kilograms] |
94.0
(25.4)
|
90.6
(18.3)
|
94.2
(25.2)
|
92.9
(23.2)
|
Outcome Measures
| Title | Change From Baseline In A1C at Week 26 |
|---|---|
| Description | A1C is measured as percent. The change from baseline is the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy. |
| Time Frame | Baseline and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline A1C measurement or at least 1 post-randomization A1C measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks. | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 156 | 151 | 153 |
| Least Squares Mean (95% Confidence Interval) [Percent] |
-0.79
|
-0.96
|
0.20
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.99 | |
| Confidence Interval |
(2-Sided) 95% -1.22 to -0.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.16 | |
| Confidence Interval |
(2-Sided) 95% -1.39 to -0.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Experiencing An Adverse Event (AE) |
|---|---|
| Description | An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy. |
| Time Frame | Up to 54 weeks (including 2 weeks following last dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants were classified according to randomized treatment. |
| Arm/Group Title | Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin |
|---|---|---|---|
| Arm/Group Description | Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
| Measure Participants | 156 | 152 | 153 |
| Number [Percentage of participants] |
64.1
41.1%
|
62.5
41.1%
|
66.7
43.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | -2.6 | |
| Confidence Interval |
(2-Sided) 95% -13.1 to 8.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Based on Miettinen & Nurminen method. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | -4.2 | |
| Confidence Interval |
(2-Sided) 95% -14.8 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Based on Miettinen & Nurminen method. | |
| Title | Percentage of Participants Discontinuing Study Treatment Due to an AE |
|---|---|
| Description | An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy. |
| Time Frame | Up to 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants were classified according to randomized treatment. |
| Arm/Group Title | Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin |
|---|---|---|---|
| Arm/Group Description | Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. |
| Measure Participants | 156 | 152 | 153 |
| Number [Percentage of participants] |
4.5
2.9%
|
3.9
2.6%
|
6.5
4.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -7.7 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Based on Miettinen & Nurminen method. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | -2.6 | |
| Confidence Interval |
(2-Sided) 95% -8.2 to 2.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Based on Miettinen & Nurminen method. | |
| Title | Change From Baseline in FPG at Week 26 |
|---|---|
| Description | The change from baseline is the Week 26 FPG minus the Week 0 FPG. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of glycemic rescue therapy. |
| Time Frame | Baseline and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline FPG measurement or at least 1 post-randomization FPG measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 155 | 152 | 153 |
| Least Squares Mean (95% Confidence Interval) [mg/dL] |
-33.96
|
-43.44
|
0.57
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -34.53 | |
| Confidence Interval |
(2-Sided) 95% -42.76 to -26.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -44.01 | |
| Confidence Interval |
(2-Sided) 95% -52.28 to -35.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Body Weight at Week 26 |
|---|---|
| Description | The change from baseline is the Week 26 body weight minus the Week 0 body weight. Data presented exclude data following the initiation of rescue therapy. |
| Time Frame | Baseline and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline body weight measurement or at least 1 post-randomization body weight measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks. | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 156 | 152 | 153 |
| Least Squares Mean (95% Confidence Interval) [Kilograms] |
-3.18
|
-3.58
|
-1.42
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.76 | |
| Confidence Interval |
(2-Sided) 95% -2.57 to -0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -2.16 | |
| Confidence Interval |
(2-Sided) 95% -2.98 to -1.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26 |
|---|---|
| Description | A1C is measured as percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy. |
| Time Frame | Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline A1C measurement or at least 1 post-randomization A1C measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 156 | 151 | 153 |
| Number [Percentage of participants] |
28.2
18.1%
|
35.8
23.6%
|
13.1
8.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Fixed effects for treatment, prior antihyperglycemic medication, covariates for baseline A1C and baseline eGFR. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.59 | |
| Confidence Interval |
(2-Sided) 95% 1.85 to 6.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | Fixed effects for treatment, prior antihyperglycemic medication, covariates for baseline A1C and baseline | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 6.77 | |
| Confidence Interval |
(2-Sided) 95% 3.46 to 13.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level |
|---|---|
| Description | Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the Mixed Meal Tolerance Test (MMTT). Change from baseline in 2-hr PPG level at Week 26 data are presented in the following outcome measure. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who had a baseline 2-hr PPG measurement. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks. | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 145 | 141 | 150 |
| Mean (Standard Deviation) [mg/dL] |
260.32
(76.110)
|
262.91
(78.189)
|
256.21
(76.917)
|
| Title | Change From Baseline in 2-hr PPG at Week 26 |
|---|---|
| Description | The change from baseline is the Week 26 2-hr PPG minus the Week 0 2-hr PPG. Laboratory measurements were performed 120 minutes following the start of the administration of the meal for the MMTT. Data presented exclude data following the initiation of rescue therapy. |
| Time Frame | Baseline and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline 2-hr PPG measurement or at least 1 post-randomization 2-hr PPG measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 153 | 148 | 151 |
| Least Squares Mean (95% Confidence Interval) [mg/dL] |
-64.15
|
-62.45
|
4.88
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -69.03 | |
| Confidence Interval |
(2-Sided) 95% -83.24 to -54.83 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -67.33 | |
| Confidence Interval |
(2-Sided) 95% -81.73 to -52.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Baseline Sitting Systolic Blood Pressure (SBP) |
|---|---|
| Description | Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in SBP at Week 26 data are presented in the following outcome measure. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who had a baseline SBP measurement. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks. | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 155 | 152 | 150 |
| Mean (Standard Deviation) [mmHg] |
130.49
(13.511)
|
129.67
(14.208)
|
129.80
(14.464)
|
| Title | Change From Baseline in SBP at Week 26 |
|---|---|
| Description | The change from baseline is the Week 26 SBP minus the Week 0 SBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy. |
| Time Frame | Baseline and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline SBP measurement or at least 1 post-randomization SBP measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 156 | 152 | 152 |
| Least Squares Mean (95% Confidence Interval) [mmHg] |
-5.54
|
-3.93
|
-2.22
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | Nominal p-value | |
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -3.31 | |
| Confidence Interval |
(2-Sided) 95% -5.98 to -0.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.213 |
| Comments | ||
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.71 | |
| Confidence Interval |
(2-Sided) 95% -4.40 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Baseline Sitting Diastolic Blood Pressure (DBP) |
|---|---|
| Description | Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Change from baseline in DBP at Week 26 data are presented in the following outcome measure. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who had a baseline DBP measurement. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks. | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 155 | 152 | 150 |
| Mean (Standard Deviation) [mmHg] |
78.46
(8.117)
|
78.53
(7.714)
|
78.13
(7.458)
|
| Title | Change From Baseline in DBP at Week 26 |
|---|---|
| Description | The change from baseline is the Week 26 DBP minus the Week 0 DBP. Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. Data presented exclude data following the initiation of rescue therapy. |
| Time Frame | Baseline and Week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consisted of all randomized participants who received at least 1 dose of study treatment and had a baseline DBP measurement or at least 1 post-randomization DBP measurement subsequent to at least 1 dose of study treatment. |
| Arm/Group Title | Ertugliflozin 5 mg | Ertugliflozin 15 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received ertugliflozin 5 mg once daily for 26 weeks. | Participants received ertugliflozin 15 mg once daily for 26 weeks | Participants received placebo to ertugliflozin once daily for 26 weeks. |
| Measure Participants | 156 | 152 | 152 |
| Least Squares Mean (95% Confidence Interval) [mmHg] |
-2.52
|
-1.10
|
-0.72
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 5 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.039 |
| Comments | Nominal p-value | |
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | -1.80 | |
| Confidence Interval |
(2-Sided) 95% -3.51 to -0.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ertugliflozin 15 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.669 |
| Comments | Nominal p-value | |
| Method | Constrained longitudinal data analysis | |
| Comments | Fixed effects for treatment, time, prior anti-hyperglycemic medication, baseline eGFR and the interaction of time by treatment. | |
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.37 | |
| Confidence Interval |
(2-Sided) 95% -2.09 to 1.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 54 weeks (+/- 3 days) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Data presented below include data following the initiation of rescue therapy for the entire study (ie, all data after randomization, with no upper limit on the follow-up window for participants who discontinued study drug). | |||||
| Arm/Group Title | Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin | |||
| Arm/Group Description | Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride. | |||
All Cause Mortality |
||||||
| Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/156 (7.1%) | 6/152 (3.9%) | 8/153 (5.2%) | |||
| Eye disorders | ||||||
| Papilloedema | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Retinal artery occlusion | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Ulcerative keratitis | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Blindness transient | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Pancreatitis | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Infections and infestations | ||||||
| Bacterial infection | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Cellulitis of male external genital organ | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Labyrinthitis | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Periorbital abscess | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Periorbital cellulitis | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Pneumonia | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Sepsis | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Joint injury | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus inadequate control | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Hyperglycaemia | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Intervertebral disc protrusion | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Osteoarthritis | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Breast cancer | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Hepatic cancer metastatic | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Squamous cell carcinoma of lung | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Squamous cell carcinoma of the cervix | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Nervous system disorders | ||||||
| Cerebrovascular accident | 1/156 (0.6%) | 2 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Ruptured cerebral aneurysm | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion spontaneous | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Psychiatric disorders | ||||||
| Bipolar disorder | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
| Epistaxis | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Haemoptysis | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Pneumothorax | 0/156 (0%) | 0 | 1/152 (0.7%) | 1 | 0/153 (0%) | 0 |
| Pulmonary embolism | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/156 (0%) | 0 | 0/152 (0%) | 0 | 1/153 (0.7%) | 1 |
| Hypertension | 1/156 (0.6%) | 1 | 0/152 (0%) | 0 | 0/153 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Ertugliflozin 5 mg/Ertugliflozin 5 mg | Ertugliflozin 15 mg/Ertugliflozin 15 mg | Placebo/Metformin | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 50/156 (32.1%) | 48/152 (31.6%) | 68/153 (44.4%) | |||
| Gastrointestinal disorders | ||||||
| Constipation | 11/156 (7.1%) | 11 | 2/152 (1.3%) | 2 | 4/153 (2.6%) | 4 |
| Diarrhoea | 8/156 (5.1%) | 10 | 5/152 (3.3%) | 5 | 23/153 (15%) | 26 |
| Nausea | 4/156 (2.6%) | 4 | 3/152 (2%) | 4 | 12/153 (7.8%) | 14 |
| Infections and infestations | ||||||
| Bronchitis | 5/156 (3.2%) | 5 | 1/152 (0.7%) | 1 | 8/153 (5.2%) | 9 |
| Nasopharyngitis | 8/156 (5.1%) | 8 | 11/152 (7.2%) | 12 | 6/153 (3.9%) | 7 |
| Upper respiratory tract infection | 9/156 (5.8%) | 10 | 10/152 (6.6%) | 11 | 9/153 (5.9%) | 15 |
| Urinary tract infection | 13/156 (8.3%) | 15 | 10/152 (6.6%) | 14 | 19/153 (12.4%) | 30 |
| Vulvovaginal mycotic infection | 12/156 (7.7%) | 17 | 8/152 (5.3%) | 11 | 2/153 (1.3%) | 2 |
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 2/156 (1.3%) | 4 | 6/152 (3.9%) | 14 | 10/153 (6.5%) | 23 |
| Nervous system disorders | ||||||
| Headache | 6/156 (3.8%) | 10 | 7/152 (4.6%) | 9 | 9/153 (5.9%) | 9 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Sponsor at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01958671
Other Study ID Numbers:
- 8835-003
- 2013-002519-90
- B1521022
First Posted:
Oct 9, 2013
Last Update Posted:
Sep 29, 2017
Last Verified:
Jul 1, 2017