Acute Kidney Injury
Conditions
Keywords
Acute Kidney Injury, Cardiopulmonary Bypass, CABG, Cardiac Surgery
Brief summary
This study will assess the safety and efficacy of BCT197 on acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass.
Interventions
DRUGBCT197 Part A
open label single dose administration of 10mg BCT197, 2 hours prior to surgery
DRUGPlacebo
Single dose matching placebo administered 2 prior to surgery
DRUGBCT197 Part B
BCT197 50mg single dose administered 2 hours prior to surgery
Sponsors
Novartis
Mereo BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients scheduled for elective cardiac surgery with CPB. Allowable procedures are CABG alone, aortic valve replacement or repair alone, mitral valve replacement or repair alone, CABG with aortic valve replacement or repair, and CABG with mitral valve replacement or repair. Patients with repeat surgery for any of the procedures can be included. * Patients must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) 18 kg/m2 * Have an eGFR ≥ 30 and ≤ 60 mL/min/1.73 m2 to participate in Part A, or an eGFR \> 60 mL/min/1.73 m2 to participate in Part B. Upon completion of Part A, patients with eGFR ≥ 30 mL/min/1.73 m2 may participate in Part B, with dose administered as per the dosing table
Exclusion criteria
* left ventricular ejection fraction, in the last 6 months, ≥30% * Active systemic infection or uncontrolled diabetes mellitus with a glucose ≥250 mg% at the screening assessment * Pregnant or nursing (lactating) women, * Female subjects must either: have been surgically sterilized or hysterectomized at least 6 months prior to study participation, or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to study participation. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow- up hormone level assessment is she considered not of child bearing potential, Surgical sterilization procedures or hysterectomy must be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF, OR be postmenopausal. Female subjects are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms). Female subjects 60 years of age or younger must confirm menopause by the demonstration of a plasma FSH level in the postmenopausal range according to the lab normal range. Documentation of a prior plasma FSH level is acceptable * History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of drug abuse as indicated by the laboratory assays conducted during screening or baseline * New cancer diagnosis with planned chemotherapy and/or radiation therapy, or cancer requiring ongoing chemotherapy and/or radiation therapy at the time of screening Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Function Measured at 48 Hours Post Cardiac Surgery With Cardiopulmonary Bypass Pump. | 48 hours | Median percent change from baseline in estimated Glomerular Filtration Rate (eGFR) at 48 hours postdose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Measurements of Drug in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass Pump. Pharmacokinetics Will be Measured Using Cmax | 4 days | Max serum concentration reached (ng/mL) |
Countries
Israel, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label - BCT197 BCT197 Part A | 8 |
| Randomized Double-blind BCT197 BCT197 Part B: Randomized Double-blind BCT197 | 42 |
| Randomized Double-blind BCT 197 Placebo Placebo: Placebo capsules | 41 |
| Total | 91 |
Baseline characteristics
| Characteristic | Open Label - BCT197 | Randomized Double-blind BCT197 | Randomized Double-blind BCT 197 Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 16 Participants | 14 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 26 Participants | 27 Participants | 57 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 8 Participants | 41 Participants | 40 Participants | 89 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 2 Participants | 33 Participants | 31 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 37 / 42 | 38 / 41 |
| serious Total, serious adverse events | 1 / 8 | 13 / 42 | 7 / 41 |
Outcome results
Primary
Renal Function Measured at 48 Hours Post Cardiac Surgery With Cardiopulmonary Bypass Pump.
Median percent change from baseline in estimated Glomerular Filtration Rate (eGFR) at 48 hours postdose.
Time frame: 48 hours
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label - BCT197 | Renal Function Measured at 48 Hours Post Cardiac Surgery With Cardiopulmonary Bypass Pump. | 8.68 Median percentage change |
| Randomized Double-blind BCT197 | Renal Function Measured at 48 Hours Post Cardiac Surgery With Cardiopulmonary Bypass Pump. | 77 Median percentage change |
| Randomized Double-blind BCT 197 Placebo | Renal Function Measured at 48 Hours Post Cardiac Surgery With Cardiopulmonary Bypass Pump. | 85.81 Median percentage change |
Secondary
Pharmacokinetic Measurements of Drug in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass Pump. Pharmacokinetics Will be Measured Using Cmax
Max serum concentration reached (ng/mL)
Time frame: 4 days
Population: PK Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label - BCT197 | Pharmacokinetic Measurements of Drug in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass Pump. Pharmacokinetics Will be Measured Using Cmax | 64.5 ng/mL | Standard Deviation 33.1 |
| Randomized Double-blind BCT197 | Pharmacokinetic Measurements of Drug in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass Pump. Pharmacokinetics Will be Measured Using Cmax | 206 ng/mL | Standard Deviation 64.4 |