Trial Outcomes & Findings for A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001) (NCT NCT01986855)

NCT ID: NCT01986855

Last Updated: 2018-09-10

Results Overview

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

468 participants

Primary outcome timeframe

Baseline and Week 26

Results posted on

2018-09-10

Participant Flow

The trial was conducted in 13 countries, including 171 trial centers; 1709 participants were screened and 468 were randomized.

Eligible participants began a ≥10-week metformin wash-off during which participant's antihyperglycemic agents (AHAs) could be adjusted. All participants entered a 2-week placebo run-in period.

Participant milestones

Participant milestones
Measure	Ertugliflozin 5 mg Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Overall Study STARTED	158	156	154
Overall Study Treated	158	155	154
Overall Study COMPLETED	145	142	143
Overall Study NOT COMPLETED	13	14	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Ertugliflozin 5 mg Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Overall Study Adverse Event	1	0	0
Overall Study Death	3	4	4
Overall Study Lost to Follow-up	2	1	0
Overall Study Screen Failure	0	1	0
Overall Study Participant Moved	0	0	2
Overall Study Withdrawal by Subject	7	8	5

Baseline Characteristics

Participants with baseline data for A1C.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ertugliflozin 5 mg n=158 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=155 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=154 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks	Total n=467 Participants Total of all reporting groups
Age, Continuous	66.7 Years STANDARD_DEVIATION 8.3 • n=158 Participants	67.5 Years STANDARD_DEVIATION 8.5 • n=155 Participants	67.5 Years STANDARD_DEVIATION 8.9 • n=154 Participants	67.3 Years STANDARD_DEVIATION 8.6 • n=467 Participants
Sex: Female, Male Female	74 Participants n=158 Participants	80 Participants n=155 Participants	82 Participants n=154 Participants	236 Participants n=467 Participants
Sex: Female, Male Male	84 Participants n=158 Participants	75 Participants n=155 Participants	72 Participants n=154 Participants	231 Participants n=467 Participants
Baseline Hemoglobin A1C (A1C)	8.20 Percentage STANDARD_DEVIATION 1.02 • n=154 Participants • Participants with baseline data for A1C.	8.17 Percentage STANDARD_DEVIATION 0.87 • n=151 Participants • Participants with baseline data for A1C.	8.08 Percentage STANDARD_DEVIATION 0.89 • n=152 Participants • Participants with baseline data for A1C.	8.15 Percentage STANDARD_DEVIATION 0.93 • n=457 Participants • Participants with baseline data for A1C.
Baseline Weight	89.4 Kilograms STANDARD_DEVIATION 22.5 • n=158 Participants	85.8 Kilograms STANDARD_DEVIATION 17.4 • n=155 Participants	90.4 Kilograms STANDARD_DEVIATION 18.9 • n=154 Participants	88.5 Kilograms STANDARD_DEVIATION 19.8 • n=467 Participants
Baseline Fasting Plasma Glucose (FPG)	160.9 mg/dL STANDARD_DEVIATION 56.4 • n=157 Participants • Participants with baseline data for FPG.	157.5 mg/dL STANDARD_DEVIATION 47.8 • n=155 Participants • Participants with baseline data for FPG.	156.9 mg/dL STANDARD_DEVIATION 56.4 • n=154 Participants • Participants with baseline data for FPG.	158.5 mg/dL STANDARD_DEVIATION 53.6 • n=466 Participants • Participants with baseline data for FPG.
Baseline Estimated glomerular filtration rate (eGFR) ≥30 to <45	52 Participants n=158 Participants	53 Participants n=155 Participants	54 Participants n=154 Participants	159 Participants n=467 Participants
Baseline Estimated glomerular filtration rate (eGFR) ≥45 to <60	106 Participants n=158 Participants	102 Participants n=155 Participants	100 Participants n=154 Participants	308 Participants n=467 Participants
Stratification Factor: Insulin at randomization No	69 Participants n=158 Participants	68 Participants n=155 Participants	66 Participants n=154 Participants	203 Participants n=467 Participants
Stratification Factor: Insulin at randomization Yes	89 Participants n=158 Participants	87 Participants n=155 Participants	88 Participants n=154 Participants	264 Participants n=467 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants who took at least 1 dose of study treatment and had at least 1 assessment at or after baseline for the change from baseline at Week 26 A1C endpoint.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=158 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=155 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=154 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Change From Baseline in A1C at Week 26 - Excluding Rescue Approach	-0.29 Percentage Interval -0.44 to -0.14	-0.41 Percentage Interval -0.56 to -0.27	-0.26 Percentage Interval -0.41 to -0.11

PRIMARY outcome

Timeframe: Up to 54 weeks

Population: The analysis population included all randomized participants who received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=158 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=155 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=154 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Percentage of Participants Who Experienced an Adverse Event (AE)	84.8 Percentage of participants	74.2 Percentage of participants	81.2 Percentage of participants

PRIMARY outcome

Timeframe: Up to 52 weeks

Population: The analysis population included all randomized participants who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=158 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=155 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=154 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Percentage of Participants Who Discontinued Study Treatment Due to an AE	8.2 Percentage of participants	3.9 Percentage of participants	5.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants with a Baseline eGFR of ≥45 to \<60 mL/min/1.73m\^2 and who took at least 1 dose of study treatment and had at least 1 assessment at or after baseline for the change from baseline at Week 26 A1C endpoint.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=105 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=97 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=99 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Change From Baseline in A1C at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach	-0.31 Percentage Interval -0.49 to -0.13	-0.37 Percentage Interval -0.56 to -0.18	-0.28 Percentage Interval -0.47 to -0.08

SECONDARY outcome

Timeframe: Baseline and Week 26

This change from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=105 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=97 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=99 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Change From Baseline in Body Weight at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach	-1.31 Kilograms Interval -1.86 to -0.76	-1.39 Kilograms Interval -1.97 to -0.81	0.46 Kilograms Interval -0.13 to 1.04

SECONDARY outcome

Timeframe: Baseline and Week 26

This change from baseline reflects the Week 26 sitting systolic blood pressure minus the Week 0 sitting systolic blood pressure. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=105 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=97 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=99 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Change From Baseline in Sitting Systolic Blood Pressure at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach	-2.33 mmHg Interval -4.98 to 0.33	-4.36 mmHg Interval -7.11 to -1.62	-0.90 mmHg Interval -3.73 to 1.92

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The analysis population included all randomized participants with a Baseline eGFR ≥45 to \<60 mL/min/1.73m\^2 and who took at least 1 dose of study treatment and had at least 1 assessment at or after baseline for the change from baseline at Week 26 FPG endpoint.

This change from baseline reflects the Week 26 FPG minus the Week 0 FPG. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=105 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=97 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=99 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Change From Baseline in FPG at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach	-11.76 mg/dL Interval -21.07 to -2.45	-20.47 mg/dL Interval -30.2 to -10.73	-4.95 mg/dL Interval -15.03 to 5.13

SECONDARY outcome

Timeframe: Week 26

Population: The analysis population included all randomized participants with a Baseline eGFR ≥45 to \<60 mL/min/1.73m\^2 and who took at least 1 dose of study treatment and had at least 1 assessment at Week 26 for the percentage of participants with an A1C \<7% at Week 26 endpoint.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=105 Participants Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=97 Participants Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks	Placebo n=99 Participants Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks
Percentage of Participants With A1C <7.0% (<53 mmol/Mol) at Week 26 - Baseline eGFR ≥45 to <60 mL/Min/1.73m^2 Stratum - Excluding Rescue Approach	16.2 Percentage of participants	11.3 Percentage of participants	12.1 Percentage of participants

Adverse Events

Placebo

Serious events: 24 serious events

Other events: 68 other events

Deaths: 0 deaths

Ertugliflozin 5 mg

Serious events: 26 serious events

Other events: 82 other events

Deaths: 0 deaths

Ertugliflozin 15 mg

Serious events: 30 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=154 participants at risk Placebo, oral, tablet, 5-mg or 5-mg and 10-mg tablet once daily for 52 weeks	Ertugliflozin 5 mg n=158 participants at risk Ertugliflozin, oral, 5-mg tablet once daily for 52 weeks. Participants also received a 10-mg matching placebo tablet once daily for 52 weeks.	Ertugliflozin 15 mg n=155 participants at risk Ertugliflozin, oral, 5-mg and 10-mg tablet once daily for 52 weeks
Gastrointestinal disorders Diarrhoea	5.8% 9/154 • Number of events 9 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	6.3% 10/158 • Number of events 10 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	2.6% 4/155 • Number of events 4 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Infections and infestations Bronchitis	3.9% 6/154 • Number of events 7 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	5.1% 8/158 • Number of events 8 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	1.3% 2/155 • Number of events 2 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Infections and infestations Nasopharyngitis	4.5% 7/154 • Number of events 8 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	5.7% 9/158 • Number of events 10 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	3.9% 6/155 • Number of events 6 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Infections and infestations Upper respiratory tract infection	4.5% 7/154 • Number of events 8 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	5.7% 9/158 • Number of events 9 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	7.1% 11/155 • Number of events 12 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Infections and infestations Urinary tract infection	9.7% 15/154 • Number of events 20 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	5.7% 9/158 • Number of events 11 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	7.7% 12/155 • Number of events 13 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Metabolism and nutrition disorders Hypoglycaemia	29.2% 45/154 • Number of events 216 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	31.0% 49/158 • Number of events 423 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	20.6% 32/155 • Number of events 281 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Nervous system disorders Dizziness	0.65% 1/154 • Number of events 1 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	5.7% 9/158 • Number of events 10 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	1.3% 2/155 • Number of events 2 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Respiratory, thoracic and mediastinal disorders Cough	1.3% 2/154 • Number of events 2 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	5.7% 9/158 • Number of events 9 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	1.9% 3/155 • Number of events 3 • Up to 54 weeks An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER