Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study With A 78-Week Extension To Evaluate The Efficacy And Safety Of Ertugliflozin In Subjects With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy
Summary
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EudraCT number |
2013-003290-95 |
Trial protocol |
HU SK CZ PL RO |
Global end of trial date |
03 Aug 2017
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Results information
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Results version number |
v1 |
This version publication date |
03 Aug 2018
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First version publication date |
03 Aug 2018
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-8835-007/B1521017
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02033889 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Aug 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Aug 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus and
inadequate glycemic control on metformin monotherapy. The primary study hypothesis is that at
Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for ertugliflozin is equal or above that for placebo.
The trial included a 1-week screening period, a variable interval for metformin titration (if needed), and at least an 8-week metformin stable dose period when participants discontinued and remained off any previous allowable background diabetes therapy (except for metformin), and a 2-week single-blind placebo run-in period prior to randomization, and a 26-week, double-blind, placebo-controlled treatment period followed by a 78-week double-blind, extension period.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
The following additional measures defined for this individual study were in place for
the protection of trial subjects: Glycemic rescue therapy with open-label glimepiride and basal
insulin was initiated in participants with glucose values exceeding protocol-specified values. Dosing and titration of open-label glimepiride rescue therapy were at the discretion of the Investigator. After the 26-week treatment period, participants randomized to the placebo arm received blinded glimepiride, if their fingerstick fasting glucose was ≥110 mg/dL.
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Background therapy |
The trial included a variable interval for metformin titration (if needed), and at least an 8-week metformin stable dose period when subjects discontinued and remained off any previous allowable background diabetes therapy (except for metformin). Participants received metformin ≥1500 mg/day, orally, once a day, through-out the remainder of trial. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Dec 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 11
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Country: Number of subjects enrolled |
Czech Republic: 15
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Country: Number of subjects enrolled |
Hong Kong: 36
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Country: Number of subjects enrolled |
Hungary: 60
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Country: Number of subjects enrolled |
Israel: 16
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Country: Number of subjects enrolled |
Mexico: 21
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Country: Number of subjects enrolled |
Poland: 16
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Country: Number of subjects enrolled |
Romania: 59
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Country: Number of subjects enrolled |
Russian Federation: 22
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Country: Number of subjects enrolled |
Slovakia: 50
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Country: Number of subjects enrolled |
South Africa: 111
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Country: Number of subjects enrolled |
Taiwan: 33
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
United States: 169
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Worldwide total number of subjects |
621
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EEA total number of subjects |
202
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
523
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From 65 to 84 years |
98
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85 years and over |
0
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Recruitment
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Recruitment details |
1535 participants were screened and 621 participants were randomized at clinical trial sites in 14 countries. | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Male and female participants 18 years of age at the time of the initial Screening Visit with a diagnosis of Type 2 diabetes mellitus (T2DM) in accordance with American Diabetes Association (ADA) guidelines were eligible to participate in this trial. | ||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Subject | ||||||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo/Glimepiride | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo to ertugliflozin
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Investigational medicinal product code |
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Other name |
Placebo
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo to ertugliflozin, (1 placebo ertugliflozin 5 mg tablet and/or 1 placebo ertugliflozin 10 mg tablet), orally once daily from Day 1 to Week 104.
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Investigational medicinal product name |
Glimepiride
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Investigational medicinal product code |
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Other name |
Amaryl; GLIMPID; GLIMY
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Glimepiride (Open-label) was used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) up to 26 weeks. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride was used in the 78-week extension period in participants who were not rescued with open-label glimepiride up to 26 weeks and who had a fingerstick fasting plasma glucose ≥110 mg/dL. Dosing and titration of blinded glimepiride was at the discretion of the investigator.
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Investigational medicinal product name |
Basal insulin
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Insulin glargine; Insulin Detemir; NPH Insulin; Insulin Degludec
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.
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Investigational medicinal product name |
Placebo to glimepiride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo to glimepiride was used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period and who had a fingerstick fasting plasma glucose ≥110 mg/dL. Dosing and titration of placebo to glimepiride was at the discretion of the investigator.
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
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Other name |
Glucophage XR; Carbophage SR Riomet; Fortamet Glumetza Obimet; Gluformin Dianben; Diabex Diaformin Siofor; Metfogamma
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Metformin ≥1500 mg/day, orally, once a day
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Arm title
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Ertugliflozin 5 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ertugliflozin
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Investigational medicinal product code |
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Other name |
MK-8835
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ertugliflozin 5 mg orally (1 ertugliflozin 5 mg tablet), once daily from Day 1 to Week 104.
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Investigational medicinal product name |
Placebo to ertugliflozin
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Investigational medicinal product code |
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Other name |
Placebo
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo to ertugliflozin, (1 placebo ertugliflozin 10 mg tablet), orally once daily from Day 1 to Week 104.
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Investigational medicinal product name |
Glimepiride
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Amaryl; GLIMPID; GLIMY
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Glimepiride (Open-label) was used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) up to 26 weeks. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride was used in the 78-week extension period in participants who were not rescued with open-label glimepiride up to 26 weeks and who had a fingerstick fasting plasma glucose ≥110 mg/dL. Dosing and titration of blinded glimepiride was at the discretion of the investigator.
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Investigational medicinal product name |
Basal insulin
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Insulin glargine; Insulin Detemir; NPH insulin; Degludec
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.
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Investigational medicinal product name |
Placebo to glimepiride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo to glimepiride was used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period and who had a fingerstick fasting plasma glucose ≥110 mg/dL. Dosing and titration of placebo to glimepiride was at the discretion of the investigator.
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
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Other name |
Glucophage XR; Carbophage SR Riomet; Fortamet Glumetza Obimet; Gluformin Dianben Diabex; Diaformin Siofor; Metfogamma
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Metformin ≥1500 mg/day, orally, once a day
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Arm title
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Ertugliflozin 15 mg | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ertugliflozin
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Investigational medicinal product code |
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Other name |
MK-8835
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ertugliflozin 15 mg orally (1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet), once daily from Day 1 to Week 104.
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Investigational medicinal product name |
Glimepiride
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Amaryl; GLIMPID; GLIMY
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Pharmaceutical forms |
Tablet
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||||||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Glimepiride (Open-label) was used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) up to 26 weeks. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride was used in the 78-week extension period in participants who were not rescued with open-label glimepiride up to 26 weeks and who had a fingerstick fasting plasma glucose ≥110 mg/dL. Dosing and titration of blinded glimepiride was at the discretion of the investigator.
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Investigational medicinal product name |
Basal insulin
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||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Insulin glargine; Insulin Detemir; NPH insulin; Degludec
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||||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated.
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Investigational medicinal product name |
Placebo to glimepiride
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
|
||||||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Placebo to glimepiride was used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period and who had a fingerstick fasting plasma glucose ≥110 mg/dL. Dosing and titration of placebo to glimepiride was at the discretion of the investigator.
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Glucophage XR; Carbophage SR Riomet; Fortamet Glumetza Obimet; Gluformin Dianben Diabex; Diaformin Siofor; Metfogamma
|
||||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
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Dosage and administration details |
Metformin ≥1500 mg/day, orally, once a day
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Glimepiride
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ertugliflozin 5 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ertugliflozin 15 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo/Glimepiride
|
||
Reporting group description |
Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||
Reporting group title |
Ertugliflozin 5 mg
|
||
Reporting group description |
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||
Reporting group title |
Ertugliflozin 15 mg
|
||
Reporting group description |
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met glycemic rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. |
|
|||||||||||||||||
End point title |
Change from Baseline in A1C at Week 26 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had at least one measurement of the respective endpoint at any time up to Week 26 of the trial, including baseline and post-baseline time points.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on Constrained Longitudinal Data Analysis (cLDA) model with fixed effects for treatment, time, prior anti hyperglycemic medication (Metformin monotherapy or Metformin + another anti-hyperglycemic agent, AHA), baseline eGFR (continuous), menopausal status. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-0.88
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.05 | ||||||||||||||||
upper limit |
-0.71 | ||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on Constrained Longitudinal Data Analysis (cLDA) model with fixed effects for treatment, time, prior anti hyperglycemic medication (Metformin monotherapy or Metformin + another anti-hyperglycemic agent, AHA), baseline eGFR (continuous), menopausal status. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-0.7
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.87 | ||||||||||||||||
upper limit |
-0.53 |
|
|||||||||||||||||
End point title |
Percentage of Participants Experiencing An Adverse Event (AE) (Including Rescue Approach) | ||||||||||||||||
End point 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. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment. The analysis population included all participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Up to Week 106
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Statistical analysis description |
Miettinen & Nurminen method was used to construct the 95% CI
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Point estimate |
-5.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-14 | ||||||||||||||||
upper limit |
3 | ||||||||||||||||
Statistical analysis title |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Statistical analysis description |
Miettinen & Nurminen method was used to construct the 95% CI
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Point estimate |
-0.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-8.7 | ||||||||||||||||
upper limit |
7.8 |
|
|||||||||||||||||
End point title |
Percentage of Participants Discontinuing Study Treatment Due to an AE (Including Rescue Approach) | ||||||||||||||||
End point 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. Per protocol, participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or basal insulin according to Investigator judgment. The analysis population included all participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Up to Week 104
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Statistical analysis description |
Miettinen & Nurminen method was used to construct the 95% CI
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Point estimate |
1.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-2.1 | ||||||||||||||||
upper limit |
5.4 | ||||||||||||||||
Statistical analysis title |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Statistical analysis description |
Miettinen & Nurminen method was used to construct the 95% CI
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in % vs Placebo/Glimepiride | ||||||||||||||||
Point estimate |
1
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-2.5 | ||||||||||||||||
upper limit |
4.7 |
|
|||||||||||||||||
End point title |
Change from Baseline in Fasting Plasma Glucose at Week 26 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 26 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 26 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at or after baseline.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-38.25
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-44.5 | ||||||||||||||||
upper limit |
-31.99 | ||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-26.69
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-32.9 | ||||||||||||||||
upper limit |
-20.48 |
|
|||||||||||||||||
End point title |
Change from Baseline in Body Weight at Week 26 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
The change in body weight from baseline reflects the Week 26 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at or after baseline.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-1.6
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-2.16 | ||||||||||||||||
upper limit |
-1.03 | ||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-1.67
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-2.24 | ||||||||||||||||
upper limit |
-1.11 |
|
|||||||||||||||||
End point title |
Percentage of Participants with an A1C of <7% (53 mmol/mol) at Week 26 (Logistic Regression using Multiple Imputation: Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had at least one measurement of the respective endpoint at any time up to Week 26 of the trial, including baseline and post baseline time points.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Adjusted Odds Ratio Relative to Placebo | ||||||||||||||||
Statistical analysis description |
Adjusted odds ratio based on a logistic regression model fitted with fixed effects for treatment, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), menopausal status, covariates for baseline A1C and baseline eGFR (continuous). Missing data imputed using the cLDA model fitted with fixed effects as in the primary analysis.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Parameter type |
Adjusted Odds Ratio Relative to Placebo | ||||||||||||||||
Point estimate |
4.48
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.64 | ||||||||||||||||
upper limit |
7.62 | ||||||||||||||||
Statistical analysis title |
Adjusted Odds Ratio Relative to Placebo | ||||||||||||||||
Statistical analysis description |
Adjusted odds ratio based on a logistic regression model fitted with fixed effects for treatment, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), menopausal status, covariates for baseline A1C and baseline eGFR (continuous). Missing data imputed using the cLDA model fitted with fixed effects as in the primary analysis.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Parameter type |
Adjusted Odds Ratio Relative to Placebo | ||||||||||||||||
Point estimate |
3.03
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.81 | ||||||||||||||||
upper limit |
5.06 |
|
|||||||||||||||||
End point title |
Change from Baseline in Sitting Systolic Blood Pressure at Week 26 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
This change from baseline reflects the Week 26 sitting systolic blood pressure (SBP) minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at or after baseline.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was
treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
413
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-4.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-6.81 | ||||||||||||||||
upper limit |
-2.19 | ||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.002 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-3.68
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-5.96 | ||||||||||||||||
upper limit |
-1.39 |
|
|||||||||||||||||
End point title |
Change from Baseline in Sitting Diastolic Blood Pressure at Week 26 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
This change from baseline reflects the Week 26 sitting diastolic blood pressure (DBP) minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who took at least one dose of study medication and had at least one assessment of the respective endpoint at or after baseline.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was
treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
413
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-2.42
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-3.86 | ||||||||||||||||
upper limit |
-0.98 | ||||||||||||||||
Statistical analysis title |
Difference in Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on the cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was
treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.013 | ||||||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||||||
Parameter type |
Difference in Least Squares Means | ||||||||||||||||
Point estimate |
-1.82
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-3.24 | ||||||||||||||||
upper limit |
-0.39 |
|
|||||||||||||||||
End point title |
Percentage of Participants with an A1C of <6.5% (48 mmol/mol) at Week 26 (Logistic Regression using Multiple Imputation: Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had at least one measurement of the respective endpoint at any time up to Week 26 of the trial, including baseline and post baseline time points.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Adjusted Odds Ratio | ||||||||||||||||
Statistical analysis description |
Adjusted odds ratio based on a logistic regression model fitted with fixed effects for treatment, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), menopausal status, covariates for baseline A1C and baseline eGFR (continuous). Missing data imputed using the cLDA model fitted with fixed effects as in the primary analysis.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Parameter type |
Adjusted Odds Ratio | ||||||||||||||||
Point estimate |
5.41
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
2.1 | ||||||||||||||||
upper limit |
13.9 | ||||||||||||||||
Statistical analysis title |
Adjusted Odds Ratio | ||||||||||||||||
Statistical analysis description |
Adjusted odds ratio based on a logistic regression model fitted with fixed effects for treatment, prior antihyperglycemic medication (metformin monotherapy or metformin + another AHA), menopausal status, covariates for baseline A1C and baseline eGFR (continuous). Missing data imputed using the cLDA model fitted with fixed effects as in the primary analysis.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.023 | ||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||
Parameter type |
Adjusted Odds Ratio | ||||||||||||||||
Point estimate |
3.1
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
1.17 | ||||||||||||||||
upper limit |
8.22 |
|
|||||||||||||||||
End point title |
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 26 | ||||||||||||||||
End point description |
Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. The analysis population included all participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in % vs Placebo | ||||||||||||||||
Statistical analysis description |
Miettinen & Nurminen method was used to construct both the 95% CI and derive p-value for the difference between the proportions (i.e. percentages).
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Miettinen & Nurminen method | ||||||||||||||||
Parameter type |
Difference in % vs Placebo | ||||||||||||||||
Point estimate |
-16.2
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-22.2 | ||||||||||||||||
upper limit |
-11.2 | ||||||||||||||||
Statistical analysis title |
Difference in % vs Placebo | ||||||||||||||||
Statistical analysis description |
Miettinen & Nurminen method was used to construct both the 95% CI and derive p-value for the difference between the proportions (i.e. percentages).
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
Miettinen & Nurminen method. | ||||||||||||||||
Parameter type |
Difference in % vs Placebo | ||||||||||||||||
Point estimate |
-14.8
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-20.9 | ||||||||||||||||
upper limit |
-9.4 |
|
|||||||||||||||||||||
End point title |
Time to Glycemic Rescue Therapy at Week 26 | ||||||||||||||||||||
End point description |
Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. The analysis population included all participants who received at least one dose of investigational product.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 26
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Log Rank | ||||||||||||||||||||
Statistical analysis description |
Based on the Log-Rank Test for the comparison to Placebo.
|
||||||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
414
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
Logrank | ||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
Statistical analysis title |
Log Rank | ||||||||||||||||||||
Statistical analysis description |
Based on the Log-Rank Test for the comparison to Placebo.
|
||||||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||||||
Number of subjects included in analysis |
416
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
|||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||
Method |
Logrank | ||||||||||||||||||||
Confidence interval |
|
|||||||||||||||||
End point title |
Change from Baseline in A1C at Week 52 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 52 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Fasting Plasma Glucose at Week 52 (Excluding Rescue Therapy) | ||||||||||||||||
End point description |
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with an A1C of <7% (53 mmol/mol) at Week 52 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with an A1C of <6.5% (48 mmol/mol) at Week 52 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 52 | ||||||||||||||||
End point description |
Per protocol, participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. The analysis population included all participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Body Weight at Week 52 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
The change in body weight from baseline reflects the Week 52 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Sitting Systolic Blood Pressure at Week 52 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
This change from baseline reflects the Week 52 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Sitting Diastolic Blood Pressure at Week 52 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
This change from baseline reflects the Week 52 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in A1C at Week 104 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 104 A1C minus the Week 0 A1C. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who had received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Fasting Plasma Glucose at Week 104 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
Blood glucose was measured on a fasting basis. Blood was drawn at predose on Day 1 and after 104 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 104 minus FPG at Week 0). Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with an A1C of <7% (53 mmol/mol) at Week 104 (Excluding Rescue approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants with an A1C of <6.5% (48 mmol/mol) at Week 104 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage of Participants Receiving Glycemic Rescue Therapy up to Week 104 | ||||||||||||||||
End point description |
Per protocol participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. The analysis population included all randomized participants who received at least one dose of investigational product.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Body Weight at Week 104 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
The change in body weight from baseline reflects the Week 104 body weight minus the Week 0 body weight. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Sitting Systolic Blood Pressure at Week 104 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
This change from baseline reflects the Week 104 sitting SBP minus the Week 0 sitting SBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change from Baseline in Sitting Diastolic Blood Pressure at Week 104 (Excluding Rescue Approach) | ||||||||||||||||
End point description |
This change from baseline reflects the Week 104 sitting DBP minus the Week 0 sitting DBP. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Ertugliflozin Plasma Concentrations (ng/mL): Summary Statistics Over Time (Excluding Rescue Approach) | ||||||||||||||||||||||||||||||||||||||||
End point description |
Pharmacokinetic samples were collected at approximately 24 hours following the prior day’s dose and before administration of the current day’s dose. The lower limit of quantitation (LLOQ) was 0.500 mg/mL. Participants who met pre-specified glycemic criteria were rescued with oral tablets of open-label glimepiride or basal insulin injected subcutaneously, and dosed according to Investigator judgment. Per protocol, this data set excludes data for any participant after the initiation of glycemic rescue therapy. A value of 9999 indicates that data for this field was not available as it was below the lower limit of quantification for these assays. The analysis population included all participants as treated (including those with all concentrations below the lower limit of quantification) and was included in the calculation of the summary statistics. Numbers of participants with non-missing concentrations at the respective time points are displayed.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose and/or 60 minutes post-dose on Weeks 6, 12, 18, and 30
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 26 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
391
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.23
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
97% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.83 | ||||||||||||||||
upper limit |
0.37 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
380
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.1
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.71 | ||||||||||||||||
upper limit |
0.5 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 26 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the femoral neck was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
391
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.3
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.38 | ||||||||||||||||
upper limit |
0.99 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
381
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.7
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0 | ||||||||||||||||
upper limit |
1.39 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 26 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the total hip was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
381
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.27
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.15 | ||||||||||||||||
upper limit |
0.68 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
391
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.08
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.33 | ||||||||||||||||
upper limit |
0.48 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 26 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the distal forearm was assessed by DXA at Week 0 and Week 26. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
390
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.21
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.78 | ||||||||||||||||
upper limit |
0.35 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
379
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.19
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.76 | ||||||||||||||||
upper limit |
0.39 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker Carboxy-Terminal Cross-Linking Telopeptides of Type I Collagen (CTX) at Week 26 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 26.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker Procollagen Type I N-terminal Propeptide (P1NP) at Week 26 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 26.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker Parathyroid Hormone (PTH) at Week 26 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 26.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 26
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 52 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
380
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
|||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.17
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.53 | ||||||||||||||||
upper limit |
0.88 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
393
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.18
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
97% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.88 | ||||||||||||||||
upper limit |
0.51 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 52 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the femoral neck was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
393
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.2
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.51 | ||||||||||||||||
upper limit |
0.91 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
381
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.25
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.48 | ||||||||||||||||
upper limit |
0.98 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 52 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the total hip was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
381
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.5
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.95 | ||||||||||||||||
upper limit |
-0.04 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
393
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.22
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.66 | ||||||||||||||||
upper limit |
0.23 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 52 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the distal forearm was assessed by DXA at Week 0 and Week 52. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
379
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.06
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.61 | ||||||||||||||||
upper limit |
0.72 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
390
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.15
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.78 | ||||||||||||||||
upper limit |
0.49 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker CTX at Week 52 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker P1NP at Week 52 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker PTH at Week 52 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 52.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 104 as Measured by DXA at the Lumbar Spine (L1-L4) Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
393
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.28
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
97% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.06 | ||||||||||||||||
upper limit |
0.5 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
380
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.23
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.01 | ||||||||||||||||
upper limit |
0.56 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 104 as Measured by DXA at the Femoral Neck Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the femoral neck was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
381
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.27
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.58 | ||||||||||||||||
upper limit |
1.13 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
393
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.12
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.7 | ||||||||||||||||
upper limit |
0.93 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in BMD at Week 104 as Measured by DXA at the Total Hip Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the total hip was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
381
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.84
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.44 | ||||||||||||||||
upper limit |
-0.24 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
393
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the least Squares Means | ||||||||||||||||
Point estimate |
-0.54
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-1.12 | ||||||||||||||||
upper limit |
0.05 |
|
|||||||||||||||||
End point title |
Percent Change from BMD at Week 104 as Measured by DXA at the Distal Forearm Using Raw Data (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
BMD at the distal forearm was assessed by DXA at Week 0 and Week 104. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had a measurement at baseline and at least one post-baseline measurement.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 5 mg
|
||||||||||||||||
Number of subjects included in analysis |
390
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
0.18
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.5 | ||||||||||||||||
upper limit |
0.85 | ||||||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||||||
Statistical analysis description |
Based on cLDA model with fixed effects for treatment, time, prior antihyperglycemic medication (Metformin monotherapy or Metformin + another AHA), baseline eGFR (continuous), menopausal status, and the interaction of time by treatment. Time was treated as a categorical variable.
|
||||||||||||||||
Comparison groups |
Placebo/Glimepiride v Ertugliflozin 15 mg
|
||||||||||||||||
Number of subjects included in analysis |
379
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
other | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Difference in the Least Squares Means | ||||||||||||||||
Point estimate |
-0.06
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.77 | ||||||||||||||||
upper limit |
0.65 |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker CTX at Week 104 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
CTX is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker P1NP at Week 104 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
P1NP is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percent Change from Baseline in Bone Biomarker PTH at Week 104 (Excluding Bone Rescue Approach) | ||||||||||||||||
End point description |
PTH is a biochemical marker of bone resorption. Participants who exhibited a significant reduction in BMD according to the protocol defined criteria completed an unscheduled DXA scan and, if required, received bone-active therapy. This table excludes measurements obtained after initiation of bone rescue medications. The analysis population included all randomized participants who received at least one dose of investigational product and had measurements of the respective endpoint at both baseline and Week 104.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Up to Week 106
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Adverse event reporting additional description |
Participants who met pre-specified glycemic criteria were rescued with open-label glimepiride or insulin glargine according to Investigator judgment. The analysis population was all participants who received at least one dose of investigational product.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Placebo/Glimepiride
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Reporting group description |
Placebo to ertugliflozin, orally once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received blinded glimepiride. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ertugliflozin 15 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ertugliflozin 5 mg
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Reporting group description |
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Up to 26 weeks, participants meeting glycemic rescue criteria were rescued with open-label glimepiride, and if they met rescue criteria again, and they were on maximal tolerated doses of glimepiride, they received basal insulin. After Week 26, non-rescued participants who had a fasting finger-stick glucose ≥110 mg/dL received glimepiride/placebo. If a participant met glycemic rescue criteria after 26 weeks, and they were on maximal tolerated dose of glimepiride, then rescue with basal insulin was initiated. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |