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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001945-42 | EudraCT Number |
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This was a mechanistic study in patients with coronary artery disease on the effects of Serelaxin on micro- and macrovascular function.
double blind, randomized, parallel group, placebo controlled study
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Serelaxin | Experimental | Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours |
|
| Placebo | Placebo Comparator | Placebo was administered by intravenous infusion for 48 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Serelaxin | Drug | Serelaxin solution diluted in 5% glucose volume/volume (v/v) solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | Global MPRI (Myocardial Perfusion Reserve Index) is defined as ratio between mean global myocardial blood flow values at rest and during adenosine stress with Mid Perfusion Reserve Index or Midl PRI (Mid Perfusion Reserve Index) which is defined as ratio between mid myocardial blood flow values at rest and during adenosine stress | baseline to Day 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Aortic Distensibility Measured by MRI | Measurements of arterial stiffness from cardiac MRI - Mean (SD) [n] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device. (mmHg-1) | At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Clydebank | West Dumbartonshire | G81 4HX | United Kingdom | ||
| Novartis Investigative Site |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Of the 58 participants in the safety analysis set, 56 completed the treatment and follow-up period as planned (i.e. Day 30 and Day 180).
Out of the total 63 participants screened, 62 were randomized. 4 of the randomized participants did not receive study drug, and 58 did receive study drug
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| ID | Title | Description |
|---|---|---|
| FG000 | Serelaxin | Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours |
| FG001 | Placebo | Placebo was administered by intravenous infusion for 48 hours |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Serelaxin | Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours |
| BG001 | Placebo | Placebo was administered by intravenous infusion for 48 hours |
| 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 | Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points | Global MPRI (Myocardial Perfusion Reserve Index) is defined as ratio between mean global myocardial blood flow values at rest and during adenosine stress with Mid Perfusion Reserve Index or Midl PRI (Mid Perfusion Reserve Index) which is defined as ratio between mid myocardial blood flow values at rest and during adenosine stress | The Pharmacodynamic (PD) analysis set included all patients with available PD data who received any study drug and experienced no protocol deviations with relevant impact on PD data. Participants who did not receive study drug as per study protocol, i.e. a reduced infusion rate, were excluded from this analysis | Posted | Mean | 95% Confidence Interval | ratio | baseline to Day 3 |
|
Day 180
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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 | Serelaxin | Serelaxin |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Disclosure Office | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C577649 | serelaxin protein, human |
| D012065 | Relaxin |
| ID | Term |
|---|---|
| D003339 | Corpus Luteum Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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double blind, randomized, parallel group, placebo controlled study
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| Placebo | Other | 5% v/v glucose solution |
|
| Change From Baseline in Aortic Velocity |
Summary table for measurements of arterial velocity from cardiac MRI - Mean (SD) [n] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device |
| At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion |
| Change From Baseline in Augmentation Index Measured From Sphygmocor Device | Summary of values and change from baseline in augmentation index by time and treatment The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion |
| Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included The augmentation index is a ratio calculated from the blood pressure waveform, it is a measure of wave reflection and arterial stiffness. Augmentation index is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion |
| Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | Pulse wave velocity was assessed by the SphygmoCor device | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion |
| Serum Concentration of Serelaxin | Summary statistics of serelaxin serum PK concentrations Blood samples were taken to measure serelaxin concentration | Day1, Day 2, Day 3 and Day 30 after the start of infusion |
| Serum Concentration of Antibodies to Serelaxin | Frequency and percentage of anti-Serelaxin antibodies Blood samples were taken to measure antibodies to serelaxin concentration at Pre-dose on Day 1, and at Day 30 after the start of the 48h drug infusion | From pre-dose on Day 1 until Day 30 after the start of drug infusion |
| Systemic Clearance of Serelaxin | Systemic clearance was estimated using the rate of serelaxin infusion and the steady state concentration | From pre-dose on Day 1 until 48h after the start of drug infusion |
| Edinburgh |
| EHN 2XU |
| United Kingdom |
| Novartis Investigative Site | Leicester | LE3 9QP | United Kingdom |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours
| OG001 | Placebo | Placebo was administered by intravenous infusion for 48 hours |
|
|
|
| Secondary | Change From Baseline in Aortic Distensibility Measured by MRI | Measurements of arterial stiffness from cardiac MRI - Mean (SD) [n] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device. (mmHg-1) | PD Analysis Set | Posted | Mean | Standard Deviation | mmHg-1 | At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion |
|
|
|
| Secondary | Change From Baseline in Aortic Velocity | Summary table for measurements of arterial velocity from cardiac MRI - Mean (SD) [n] Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device | PD Analysis Set | Posted | Mean | Standard Deviation | cm/s | At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion |
|
|
|
| Secondary | Change From Baseline in Augmentation Index Measured From Sphygmocor Device | Summary of values and change from baseline in augmentation index by time and treatment The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance | PD Analysis Set For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included | Posted | Mean | Standard Deviation | ratio | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion |
|
|
|
| Secondary | Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance | The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included The augmentation index is a ratio calculated from the blood pressure waveform, it is a measure of wave reflection and arterial stiffness. Augmentation index is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave | PD Analysis Set | Posted | Mean | 95% Confidence Interval | ratio | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion |
|
|
|
| Secondary | Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis | Pulse wave velocity was assessed by the SphygmoCor device | The Pharmacodynamic (PD) analysis set included all patients with available PD data who received any study drug and experienced no protocol deviations with relevant impact on PD data. Any patients who had a reduced flow rate of infusion were excluded from this analysis | Posted | Mean | Standard Deviation | meters/second | Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion |
|
|
|
| Secondary | Serum Concentration of Serelaxin | Summary statistics of serelaxin serum PK concentrations Blood samples were taken to measure serelaxin concentration | Pharmacokinetic Analysis Set The PK analysis set includes all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no protocol deviations with relevant impact on PK data | Posted | Mean | Standard Deviation | pg/mL | Day1, Day 2, Day 3 and Day 30 after the start of infusion |
|
|
|
| Secondary | Serum Concentration of Antibodies to Serelaxin | Frequency and percentage of anti-Serelaxin antibodies Blood samples were taken to measure antibodies to serelaxin concentration at Pre-dose on Day 1, and at Day 30 after the start of the 48h drug infusion | Safety Analysis Set | Posted | Number | percentage of participants | From pre-dose on Day 1 until Day 30 after the start of drug infusion |
|
|
|
| Secondary | Systemic Clearance of Serelaxin | Systemic clearance was estimated using the rate of serelaxin infusion and the steady state concentration | Pharmacokinetic Analysis Set The PK analysis set includes all participants with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug and experienced no protocol deviations with relevant impact on PK data | Posted | Mean | Standard Deviation | mL/hr/kg | From pre-dose on Day 1 until 48h after the start of drug infusion |
|
|
|
| 5 |
| 30 |
| 16 |
| 30 |
| EG001 | Placebo | Placebo | 7 | 28 | 18 | 28 |
| Angina pectoris | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Angina unstable | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Type IV hypersensitivity reaction | Immune system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Cardiac procedure complication | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Vascular procedure complication | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Extrasystoles | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (19.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (19.0) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA (19.0) | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Electrocardiogram Q wave abnormal | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Glomerular filtration rate decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| QRS axis abnormal | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (19.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (19.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (19.0) | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Throat tightness | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
| Peripheral coldness | Vascular disorders | MedDRA (19.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D036361 | Peptide Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| Ascending Aorta Distensibility, Day 47 |
|
|
| Descending Aorta Distensibility, Day 0 |
|
|
| Descending Aorta Distensibility, Day 47 |
|
|
| Peak Flow Velocity (cm/s), Day 47 (n=23, 25) |
|
|
| DAY 1, 6h (n=24,26) |
|
|
| DAY 2, 24h (n=24,25) |
|
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| DAY 3, 47h (n=23,25) |
|
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| DAY 3, 50h (n=22, 24) |
|
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| DAY 3, 54h (n=22,25) |
|
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| DAY 30 (n=25, 26) |
|
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| DAY 180 (n=24,25) end of study |
|
|
| DAY 1, 6h (n=24,26) |
|
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| DAY 2, 24h (n=24,25) |
|
|
| DAY 3, 47h (n=23,25) |
|
|
| DAY 3, 50h (n=22, 24) |
|
|
| DAY 3, 54h (n=22,25) |
|
|
| DAY 30 (n=25, 26) |
|
|
| DAY 180 (n=24,25) end of study |
|
|
| DAY 2, 24hrs (n=19,24) |
|
|
| DAY 3, 47hrs (n=22,23) |
|
|
| DAY 30, 0hrs (n=23, 24) |
|
|
| DAY 3, 47hrs (n=23,25) |
|
|
| DAY 180 EOS (n=23,24) |
|
|
|
| DAY 3, 48hrs (n=22) |
|
|
| DAY 3, 50 hrs (n=21) |
|
|
| DAY 3, 54hrs, (n=22) |
|
|
| DAY 30 (n=30) |
|
|
| DAY 30 NEGATIVE |
|
| DAY 30 POSITIVE |
|