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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
This is a randomized, double-blind, double-dummy, placebo-controlled, cross over design trial with empagliflozin compared to placebo that is added to open-label ramipril.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A | Experimental | Empagliflozin followed by a wash-out followed by empagliflozin matching placebo on a background of open label ramipril. |
|
| Sequence B | Experimental | Empagliflozin matching placebo followed a wash-out followed by empagliflozin on a background of open label ramipril. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin | Drug | Empagliflozin will be taken once daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Glomerular Filtration Rate (GFR) Under Euglycaemic Conditions After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril. | 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. | At week 4 and at week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toronto General Hospital | Toronto | Ontario | M5G 2N2 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35862082 | Derived | Lytvyn Y, Kimura K, Peter N, Lai V, Tse J, Cham L, Perkins BA, Soleymanlou N, Cherney DZI. Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition. Circulation. 2022 Aug 9;146(6):450-462. doi: 10.1161/CIRCULATIONAHA.122.059150. Epub 2022 Jul 11. |
| Label | URL |
|---|---|
| Related Info | View source |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
| |||||||||||||
| Wash-out Period |
| |||||||||||||
| Treatment Period 2 |
|
Full Analysis Set (FAS): The FAS consists of all patients who were randomised, treated with at least one dose of empagliflozin/placebo and provided randomisation baseline (visit 8) and at least one post-randomisation glomerular filtration rate (GFR) measurement.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Glomerular Filtration Rate (GFR) Under Euglycaemic Conditions After 4 Weeks of Treatment With Either Empagliflozin Added to Ramipril or Placebo Added to Ramipril. | 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. | Hyperfilterers: Patients before ramipril monotherapy with GFR ≥ 135 mL/min/1.73m², as measured at screening (visit 4). | Posted | Mean | Standard Deviation | milliliter (mL) /minutes (min) /1.73m² | At week 4 and at week 12 |
|
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 25 mg Empagliflozin | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intestinal obstruction | Gastrointestinal disorders | 22.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Centre | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 3, 2018 | Jul 1, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 9, 2019 | Jul 1, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C570240 | empagliflozin |
| D017257 | Ramipril |
| ID | Term |
|---|---|
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo (matching empagliflozin) |
| Drug |
Placebo will be taken once daily |
|
| ramipril | Drug | Ramipril will be taken once or twice daily |
|
| At week 4 and at week 12. |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Glomerular filtration rate (GFR) at baseline | Mean | Standard Deviation | milliliter (mL) /minutes (min) /1.73m² |
|
| OG001 | Placebo | 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. |
|
|
| Secondary | 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 | 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. | Hyperfilterers: Patients before ramipril monotherapy with GFR ≥ 135 mL/min/1.73m², as measured at screening (visit 4). | Posted | Count of Participants | Participants | At week 4 and at week 12. |
|
|
|
| 0 |
| 31 |
| 0 |
| 31 |
| 15 |
| 31 |
| EG001 | Placebo | 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. | 0 | 30 | 2 | 30 | 13 | 30 |
| Testicular rupture | Injury, poisoning and procedural complications | 22.0 | Systematic Assessment |
|
| Thirst | General disorders | 22.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | 22.0 | Systematic Assessment |
|
| Ketosis | Metabolism and nutrition disorders | 22.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | 22.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | 22.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | 22.0 | Systematic Assessment |
|
Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days.
BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |