Trial Outcomes & Findings for A Dose Ranging Phase IIa Study of 6 Hour Intravenous Dosages of CXL-1427 in Patients Hospitalized With Heart Failure (NCT NCT02157506)

Last Updated: 2019-07-31

Results Overview

A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

70 participants

Primary outcome timeframe

30 days following the initiation of treatment

Results posted on

2019-07-31

Participant Flow

A total of 70 participants were enrolled of which only 46 participants received treatment. 24 were not treated due to screen failures, 3 of the 24 were randomized but not dosed due to other reasons.

Participant milestones

Participant milestones
Measure	Placebo Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Overall Study STARTED	12	6	9	12	7
Overall Study COMPLETED	12	5	8	12	7
Overall Study NOT COMPLETED	0	1	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Overall Study Adverse Event	0	1	0	0	0
Overall Study Lost to Follow-up	0	0	1	0	0

Baseline Characteristics

A Dose Ranging Phase IIa Study of 6 Hour Intravenous Dosages of CXL-1427 in Patients Hospitalized With Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.	Total n=46 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 9.25 • n=39 Participants	63.5 years STANDARD_DEVIATION 3.51 • n=41 Participants	61.1 years STANDARD_DEVIATION 11.36 • n=35 Participants	61.6 years STANDARD_DEVIATION 10.26 • n=31 Participants	48.3 years STANDARD_DEVIATION 17.49 • n=146 Participants	60.0 years STANDARD_DEVIATION 11.10 • n=19 Participants
Sex: Female, Male Female	2 Participants n=39 Participants	2 Participants n=41 Participants	1 Participants n=35 Participants	0 Participants n=31 Participants	2 Participants n=146 Participants	7 Participants n=19 Participants
Sex: Female, Male Male	10 Participants n=39 Participants	4 Participants n=41 Participants	8 Participants n=35 Participants	12 Participants n=31 Participants	5 Participants n=146 Participants	39 Participants n=19 Participants

PRIMARY outcome

Timeframe: 30 days following the initiation of treatment

Population: The safety analysis set consists of all randomized participants who received all or part of the infusion of the study drug.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Number of Participants With Treatment-Emergent Adverse Events At least one Severe TEAE	0 Participants	4 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one Drug-related severe TEAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one Serious TEAE	1 Participants	3 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one Drug-related fatal TEAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one TEAE leading to drug interruption	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one TEAE leading to drug discontinuation	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one Drug-related serious TEAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one Fatal TEAE	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events At least one TEAE	3 Participants	5 Participants	5 Participants	7 Participants	3 Participants

PRIMARY outcome

Timeframe: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion

Population: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.

The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion	-0.17 mm Hg Standard Deviation 2.35	-3.00 mm Hg Standard Deviation 3.06	-5.06 mm Hg Standard Deviation 3.93	-4.42 mm Hg Standard Deviation 4.00	-4.75 mm Hg Standard Deviation 3.50

PRIMARY outcome

Timeframe: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation

Population: Modified Intent-To-Treat Analysis Set: all randomized patients who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.

Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion	-0.21 mm Hg Standard Deviation 3.35	-3.69 mm Hg Standard Deviation 2.55	-4.17 mm Hg Standard Deviation 4.02	-2.67 mm Hg Standard Deviation 3.63	-3.17 mm Hg Standard Deviation 1.82

PRIMARY outcome

Timeframe: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation

Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick)	7.95 Percentage of change Standard Deviation 16.15	0.53 Percentage of change Standard Deviation 18.12	13.41 Percentage of change Standard Deviation 23.53	9.59 Percentage of change Standard Deviation 11.91	-9.58 Percentage of change Standard Deviation 18.02

SECONDARY outcome

Timeframe: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation

Pulmonary artery systolic pressure (PAS) was measured by an indwelling PA catheter. The effects of CXL-1427 on time-averaged PAS during the course of the infusion are presented

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion	-0.73 mm Hg Standard Deviation 3.73	-6.42 mm Hg Standard Deviation 2.59	-5.98 mm Hg Standard Deviation 5.31	-6.26 mm Hg Standard Deviation 5.09	-4.24 mm Hg Standard Deviation 5.24

SECONDARY outcome

Timeframe: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation

The effects of CXL-1427 on time-averaged RAP during the course of the infusion are presented

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion	-0.03 mm Hg Standard Deviation 2.61	-1.92 mm Hg Standard Deviation 2.91	-2.08 mm Hg Standard Deviation 3.10	-2.17 mm Hg Standard Deviation 2.42	-4.60 mm Hg Standard Deviation 3.23

SECONDARY outcome

Timeframe: Baseline, Hour 24 after infusion, Follow-up visit 1

Mean arterial pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion	-1.11 mm Hg Standard Deviation 5.01	-5.84 mm Hg Standard Deviation 4.46	-4.75 mm Hg Standard Deviation 10.93	-7.16 mm Hg Standard Deviation 7.67	-6.69 mm Hg Standard Deviation 5.67

SECONDARY outcome

Timeframe: Baseline, Hour 24 after infusion, Follow-up visit 1

Mean Time-Averaged Change from Baseline in Systolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion	-3.15 mm Hg Standard Deviation 5.53	-8.69 mm Hg Standard Deviation 4.43	-2.41 mm Hg Standard Deviation 12.57	-6.81 mm Hg Standard Deviation 9.54	-4.64 mm Hg Standard Deviation 4.04

SECONDARY outcome

Timeframe: Baseline, Hour 24 after infusion, Follow-up visit 1

Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion	-0.09 mm Hg Standard Deviation 8.30	-4.42 mm Hg Standard Deviation 5.22	-5.93 mm Hg Standard Deviation 11.07	-7.33 mm Hg Standard Deviation 8.51	-7.71 mm Hg Standard Deviation 8.03

SECONDARY outcome

Timeframe: Baseline, Hour 24 after infusion, Follow-up visit 1

Mean Time-Averaged Change from Baseline in Heart Rate during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3μg/kg/Min n=6 Participants Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5μg/kg/Min n=9 Participants Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7μg/kg/Min n=12 Participants Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12μg/kg/Min n=7 Participants Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion	-0.79 Beats/min Standard Deviation 6.34	1.06 Beats/min Standard Deviation 3.74	-3.09 Beats/min Standard Deviation 6.84	1.00 Beats/min Standard Deviation 7.08	-4.52 Beats/min Standard Deviation 16.92

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

CXL-1427 3 μg/kg/Min

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

CXL-1427 5 μg/kg/Min

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

CXL-1427 7 μg/kg/Min

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

CXL-1427 12 μg/kg/Min

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=12 participants at risk Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3 μg/kg/Min n=6 participants at risk Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5 μg/kg/Min n=9 participants at risk Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7 μg/kg/Min n=12 participants at risk Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12 μg/kg/Min n=7 participants at risk Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Cardiac disorders Atrial flutter	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Atrioventricular block complete	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	14.3% 1/7 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Cardiac failure	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	11.1% 1/9 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Infections and infestations Rhinovirus infection	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Renal and urinary disorders Renal failure	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Skin and subcutaneous tissue disorders Toxic epidermal necrolysis	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.

Other adverse events

Other adverse events
Measure	Placebo n=12 participants at risk Subjects received matching placebo intravenous (IV) infusion.	CXL-1427 3 μg/kg/Min n=6 participants at risk Subjects received CXL-1427 3 microgram per kilogram per minute (μg/kg/min) IV infusion as 90 milliliter (mL) of dosing solution at a rate of 15 milliliter per hour (mL/hour) for six hours.	CXL-1427 5 μg/kg/Min n=9 participants at risk Subjects received CXL-1427 5 μg/kg/min IV infusion as 90 mL of dosing solution at a rate of 15 mL/hour for six hours.	CXL-1427 7 μg/kg/Min n=12 participants at risk Subjects received CXL-1427 7 μg/kg/min IV infusion as 150 mL of dosing solution at a rate of 25 mL/hour for six hours.	CXL-1427 12 μg/kg/Min n=7 participants at risk Subjects received CXL-1427 12 μg/kg/min IV infusion as 180 mL of dosing solution at a rate of 30 mL/hour for six hours.
Cardiac disorders Atrial flutter	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Atrioventricular block complete	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	14.3% 1/7 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Cardiac failure	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	11.1% 1/9 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	11.1% 1/9 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Cardiorenal syndrome	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	11.1% 1/9 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Low cardiac output syndrome	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	14.3% 1/7 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Tachycardia	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Cardiac disorders Ventricular tachycardia	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
General disorders Catheter site haemorrhage	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
General disorders Chest pain	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	11.1% 1/9 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Infections and infestations Rhinovirus infection	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Infections and infestations Urinary tract infection	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Investigations Blood creatinine increased	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Nervous system disorders Dizziness	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Nervous system disorders Headache	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 2/12 • Number of events 2 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	14.3% 1/7 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Nervous system disorders Syncope	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	14.3% 1/7 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Psychiatric disorders Psychotic disorder	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Renal and urinary disorders Renal failure	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Skin and subcutaneous tissue disorders Toxic epidermal necrolysis	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	16.7% 1/6 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/9 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/7 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.
Vascular disorders Hypotension	8.3% 1/12 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/6 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	33.3% 3/9 • Number of events 3 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	0.00% 0/12 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.	14.3% 1/7 • Number of events 1 • All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.

Additional Information

EU Study Start-Up Unit

Bristol-Myers Squibb International Corporation

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER