Trial Outcomes & Findings for Empagliflozin and ACEi- Effects on Hyperfiltration: BETWEEN Study (NCT NCT02632747)
NCT ID: NCT02632747
Last Updated: 2020-07-24
Results Overview
Glomerular filtration rate (GFR) under euglycaemic conditions after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
At week 4 and at week 12
Results posted on
2020-07-24
Participant Flow
A randomized, double-blinded, placebo-controlled, crossover trial to compare the effect of empagliflozin versus placebo when added to ramipril on reducing glomerular hyperfiltration in patients with type 1 Diabetes mellitus (T1D), Type 2 Diabetes (T2D), or obesity.
Participants who successfully completed the 4 weeks open-label ramipril run-in period and meet all of the inclusion, and non of the exclusion criteria were randomized into the trial, with no stratification to one of two sequences.
Participant milestones
| Measure |
Sequence A: 25 mg Empagliflozin / Placebo
During dosing Period 1, participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose for 4 weeks added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg ramipril or to their maximum tolerated dose. This was followed by a 4-week wash-out period with background treatment of open-label ramipril administered orally as capsule once or twice daily as prescribed by the investigator,and then followed by 4 weeks of dosing period 2 of 1 tablet matching placebo administered once daily as single oral dose added to open-label Ramipril.
|
Sequence B: Placebo / 25 mg Empagliflozin
During dosing Period 1, participants were administered 1 tablet of matching placebo once daily as single oral dose for 4 weeks added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg ramipril or to their maximum tolerated dose. This was followed by a 4-week wash-out period with background treatment of open-label ramipril administered orally as capsule once or twice daily as prescribed by the investigator,and then followed by 4 weeks of dosing period 2 of 1 tablet of 25 mg empagliflozin administered once daily as single oral dose added to open-label Ramipril.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
16
|
15
|
|
Treatment Period 1
COMPLETED
|
16
|
15
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Wash-out Period
STARTED
|
16
|
15
|
|
Wash-out Period
COMPLETED
|
15
|
15
|
|
Wash-out Period
NOT COMPLETED
|
1
|
0
|
|
Treatment Period 2
STARTED
|
15
|
15
|
|
Treatment Period 2
COMPLETED
|
15
|
15
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence A: 25 mg Empagliflozin / Placebo
During dosing Period 1, participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose for 4 weeks added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg ramipril or to their maximum tolerated dose. This was followed by a 4-week wash-out period with background treatment of open-label ramipril administered orally as capsule once or twice daily as prescribed by the investigator,and then followed by 4 weeks of dosing period 2 of 1 tablet matching placebo administered once daily as single oral dose added to open-label Ramipril.
|
Sequence B: Placebo / 25 mg Empagliflozin
During dosing Period 1, participants were administered 1 tablet of matching placebo once daily as single oral dose for 4 weeks added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg ramipril or to their maximum tolerated dose. This was followed by a 4-week wash-out period with background treatment of open-label ramipril administered orally as capsule once or twice daily as prescribed by the investigator,and then followed by 4 weeks of dosing period 2 of 1 tablet of 25 mg empagliflozin administered once daily as single oral dose added to open-label Ramipril.
|
|---|---|---|
|
Wash-out Period
Adverse Event
|
1
|
0
|
Baseline Characteristics
Empagliflozin and ACEi- Effects on Hyperfiltration: BETWEEN Study
Baseline characteristics by cohort
| Measure |
Sequence A: 25 mg Empagliflozin / Placebo
n=16 Participants
During dosing Period 1, participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose for 4 weeks added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg ramipril or to their maximum tolerated dose. This was followed by a 4-week wash-out period with background treatment of open-label ramipril administered orally as capsule once or twice daily as prescribed by the investigator,and then followed by 4 weeks of dosing period 2 of 1 tablet matching placebo administered once daily as single oral dose added to open-label Ramipril.
|
Sequence B: Placebo / 25 mg Empagliflozin
n=14 Participants
During dosing Period 1, participants were administered 1 tablet of matching placebo once daily as single oral dose for 4 weeks added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg ramipril or to their maximum tolerated dose. This was followed by a 4-week wash-out period with background treatment of open-label ramipril administered orally as capsule once or twice daily as prescribed by the investigator,and then followed by 4 weeks of dosing period 2 of 1 tablet of 25 mg empagliflozin administered once daily as single oral dose added to open-label Ramipril.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.5 Years
STANDARD_DEVIATION 4.2 • n=5 Participants
|
27.0 Years
STANDARD_DEVIATION 5.0 • n=7 Participants
|
26.7 Years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Glomerular filtration rate (GFR) at baseline
|
113.6 milliliter (mL) /minutes (min) /1.73m²
STANDARD_DEVIATION 9.4 • n=5 Participants
|
115.7 milliliter (mL) /minutes (min) /1.73m²
STANDARD_DEVIATION 14.0 • n=7 Participants
|
114.6 milliliter (mL) /minutes (min) /1.73m²
STANDARD_DEVIATION 11.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: At week 4 and at week 12Population: Hyperfilterers: Patients before ramipril monotherapy with GFR ≥ 135 mL/min/1.73m², as measured at screening (visit 4).
Glomerular filtration rate (GFR) under euglycaemic conditions after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.
Outcome measures
| Measure |
25 mg Empagliflozin
n=2 Participants
Participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
Placebo
n=2 Participants
Participants were administered 1 tablet of matching placebo administered once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
|---|---|---|
|
Glomerular Filtration Rate (GFR) Under Euglycaemic Conditions After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril.
|
124.0 milliliter (mL) /minutes (min) /1.73m²
Standard Deviation 10.61
|
132.5 milliliter (mL) /minutes (min) /1.73m²
Standard Deviation 7.78
|
SECONDARY outcome
Timeframe: At week 4 and at week 12.Population: Hyperfilterers: Patients before ramipril monotherapy with GFR ≥ 135 mL/min/1.73m², as measured at screening (visit 4).
Filtration status (Glomerular Filtration Rate (GFR) \< 120 mL/min/1.73m²) after 4 weeks of treatment with either empagliflozin added to ramipril or placebo added to ramipril. Filtration status is defined as whether a patient has normal Filtration status (GFR \< mL/min/1.73m², "yes") or not (GFR ≥ mL/min/1.73m², "no"). The pre-specified statistical analysis was not conducted, because data are too sparse in the subgroup of hyperfilterers.
Outcome measures
| Measure |
25 mg Empagliflozin
n=2 Participants
Participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
Placebo
n=2 Participants
Participants were administered 1 tablet of matching placebo administered once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
|---|---|---|
|
Filtration Status (Glomerular Filtration Rate (GFR) < 120 mL/Min/1.73m², Yes/no) After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril
Yes
|
1 Participants
|
0 Participants
|
|
Filtration Status (Glomerular Filtration Rate (GFR) < 120 mL/Min/1.73m², Yes/no) After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril
No
|
1 Participants
|
2 Participants
|
Adverse Events
25 mg Empagliflozin
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
25 mg Empagliflozin
n=31 participants at risk
Participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
Placebo
n=30 participants at risk
Participants were administered 1 tablet of matching placebo administered once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
|---|---|---|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
3.3%
1/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
Injury, poisoning and procedural complications
Testicular rupture
|
0.00%
0/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
3.3%
1/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
Other adverse events
| Measure |
25 mg Empagliflozin
n=31 participants at risk
Participants were administered 1 tablet of 25 milligram (mg) empagliflozin once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
Placebo
n=30 participants at risk
Participants were administered 1 tablet of matching placebo administered once daily as single oral dose, added to open-label Ramipril, where participants had been dose escalated from 1.25, 5, 7.5, or 10 mg, up to 10 mg Ramipril or to their maximum tolerated dose.
|
|---|---|---|
|
General disorders
Fatigue
|
9.7%
3/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
0.00%
0/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
General disorders
Thirst
|
6.5%
2/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
0.00%
0/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
Infections and infestations
Nasopharyngitis
|
9.7%
3/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
23.3%
7/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
Metabolism and nutrition disorders
Ketosis
|
19.4%
6/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
3.3%
1/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
Nervous system disorders
Dizziness
|
6.5%
2/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
3.3%
1/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
Nervous system disorders
Headache
|
9.7%
3/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
10.0%
3/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/31 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
10.0%
3/30 • From drug administration until 7 days after the last dose of treatment, up to 91 days.
Treated Set (TS): All participants who were randomized and treated with at least one dose of double-blind study medication (empagliflozin, placebo).
|
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
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- Publication restrictions are in place
Restriction type: OTHER