Trial Outcomes & Findings for A Study of CLR325 in Chronic Stable Heart Failure Patients. (NCT NCT02696967)

Last Updated: 2021-01-05

Results Overview

Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that CLR325 is safe for the treatment of chronic stable heart-failure patients through the monitoring of relevant clinical and laboratory safety parameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Day 1 to 28

Results posted on

2021-01-05

Participant Flow

This study was conducted in 11 centers in 5 countries: Belgium (1), Germany (2), Netherlands (1), Singapore (1) and USA (6).

Patients were assigned to one of the 2 treatment arms in fixed randomization ratio (CLR325: Placebo): * Cohort 1: Single dose of CLR325 2.5 mcg/kg/min (i.v.) or placebo (i.v.) * Cohort 2: Single dose of CLR325 0.25 mcg/kg/min (i.v.) or placebo (i.v.) * Cohort 3: Single dose of CLR325 8 mcg/kg/min (i.v.) or placebo (i.v.)

Participant milestones

Participant milestones
Measure	CLR325 0.25 mcg/kg/Min Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Overall Study STARTED	4	6	6	10
Overall Study Pharmacokinetic (PK) Analysis Set	4	6	4	0
Overall Study COMPLETED	4	6	6	10
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of CLR325 in Chronic Stable Heart Failure Patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo n=10 Participants Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.	Total n=26 Participants Total of all reporting groups
Age, Continuous	56.5 Years STANDARD_DEVIATION 3.1 • n=5 Participants	55.2 Years STANDARD_DEVIATION 13.0 • n=7 Participants	63.5 Years STANDARD_DEVIATION 11.8 • n=5 Participants	54.2 Years STANDARD_DEVIATION 9.2 • n=4 Participants	56.9 Years STANDARD_DEVIATION 10.4 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants	23 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants	19 Participants n=21 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to 28

Population: The Safety population, which consisted of all patients who had been exposed to at least one infusion of study drug or placebo, was considered.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo n=10 Participants Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Number of Patients With Adverse Events, Serious Adverse Events and Death On-treatment Adverse Event (AEs)	1 Participants	2 Participants	4 Participants	7 Participants
Number of Patients With Adverse Events, Serious Adverse Events and Death On-treatment Serious Adverse Event (SAEs)	0 Participants	2 Participants	2 Participants	0 Participants
Number of Patients With Adverse Events, Serious Adverse Events and Death On-treatment Deaths	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, and 18 hours post start of CLR325 infusion on Day 1

Population: Participants from the Pharmacokinetic (PK) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PK concentration measurement, with data available for analysis were considered.

AUC0-18hr is the area under the plasma concentration-time curve from time zero to 18 hours after the start of CLR325 infusion. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to 18 Hours (AUC0-18hr) CLR 325	1220 ng*hr/mL Geometric Coefficient of Variation 10.4	18500 ng*hr/mL Geometric Coefficient of Variation 31.6	79700 ng*hr/mL Geometric Coefficient of Variation 32.5	—
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to 18 Hours (AUC0-18hr) CQJ295	NA ng*hr/mL Geometric Coefficient of Variation NA N/A: Not Estimable (CQJ295 concentration below lower limit of quantification (LLOQ))	623 ng*hr/mL Geometric Coefficient of Variation 102.3	5560 ng*hr/mL Geometric Coefficient of Variation 46.7	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

AUC0-28hr is the area under the plasma concentration-time curve from time zero to 28 hours after the start of CLR325 infusion. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From From Time Zero to 28 Hours (AUC0-28hrs) CLR325	1460 ng*hr/mL Geometric Coefficient of Variation 12.8	21500 ng*hr/mL Geometric Coefficient of Variation 32.9	100000 ng*hr/mL Geometric Coefficient of Variation 28.2	—
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From From Time Zero to 28 Hours (AUC0-28hrs) CQJ295	NA ng*hr/mL Geometric Coefficient of Variation NA N/A: Not Estimable (CQJ295 concentration below lower limit of quantification (LLOQ))	838 ng*hr/mL Geometric Coefficient of Variation 106.2	8390 ng*hr/mL Geometric Coefficient of Variation 43.5	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

AUCinf is the area under the plasma concentration-time curve from time zero to infinity. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=2 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) CLR325	1510 ng*hr/mL Geometric Coefficient of Variation 4.7	21900 ng*hr/mL Geometric Coefficient of Variation 34.0	103000 ng*hr/mL Geometric Coefficient of Variation 26.1	—
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) CQJ295	—	843 ng*hr/mL Geometric Coefficient of Variation 49.9	9660 ng*hr/mL Geometric Coefficient of Variation 38.5	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

AUClast is the area under the plasma concentration-time curve from time zero to the last measurable concentration sampling time. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) CLR325	1450 ng*hr/mL Geometric Coefficient of Variation 13.0	21500 ng*hr/mL Geometric Coefficient of Variation 32.9	100000 ng*hr/mL Geometric Coefficient of Variation 28.2	—
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) CQJ295	3.10 ng*hr/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	836 ng*hr/mL Geometric Coefficient of Variation 107.1	8380 ng*hr/mL Geometric Coefficient of Variation 43.6	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

CL is the systemic (or total body) clearance from plasma following CLR325 infusion. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325: Clearance From Plasma (CL) Following Drug Administration	15200 mL/hr Geometric Coefficient of Variation 6.1	13200 mL/hr Geometric Coefficient of Variation 54.9	7460 mL/hr Geometric Coefficient of Variation 15.4	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

Cmax,ss is the observed maximum plasma concentration following drug administration at steady state. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) CLR325	103 ng/mL Geometric Coefficient of Variation 11.2	1370 ng/mL Geometric Coefficient of Variation 36.0	6080 ng/mL Geometric Coefficient of Variation 38.4	—
Pharmacokinetic of CLR325 and CQJ295: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss) CQJ295	NA ng/mL Geometric Coefficient of Variation NA N/A: Not Estimable (CQJ295 concentration below lower limit of quantification (LLOQ))	54.2 ng/mL Geometric Coefficient of Variation 91.0	468 ng/mL Geometric Coefficient of Variation 54.0	—

SECONDARY outcome

Timeframe: 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

T\^1/2 is the elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=2 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Terminal Elimination Half-life (T1/2) CLR325	1.86 hr Standard Deviation 0.197	2.99 hr Standard Deviation 0.520	2.96 hr Standard Deviation 0.992	—
Pharmacokinetic of CLR325 and CQJ295: Terminal Elimination Half-life (T1/2) CQJ295	—	3.12 hr Standard Deviation 0.275	5.73 hr Standard Deviation 3.38	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

Tmax is the time to reach maximum plasma concentration after single dose administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Time to Reach the Maximum Concentration After Drug Administration (TMax) CLR325	14.0 hr Interval 4.93 to 18.0	12.0 hr Interval 8.05 to 12.1	14.9 hr Interval 8.08 to 17.9	—
Pharmacokinetic of CLR325 and CQJ295: Time to Reach the Maximum Concentration After Drug Administration (TMax) CQJ295	0 hr Interval 0.0 to 5.03	15.1 hr Interval 7.92 to 18.1	17.9 hr Interval 8.33 to 18.1	—

SECONDARY outcome

Timeframe: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

Vss is the volume of distribution at steady state following intravenous administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325: Volume of Distribution at Steady State Following Intravenous Administration (Vss)	51600 mL Geometric Coefficient of Variation 19.6	32500 mL Geometric Coefficient of Variation 47.6	28000 mL Geometric Coefficient of Variation 33.3	—

SECONDARY outcome

Timeframe: 0-28 hours on Day 1

Ae 0-28 hours is the amount of drug (or defined metabolite) excreted into the urine from time zero to 28 hours after the start of CLR325 infusion. The urine PK parameters were measured using an non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Amount of Drug (or Defined Metabolite) Excreted Into the Urine From Time (Ae 0-28 Hours) CLR325	NA ng Geometric Coefficient of Variation NA N/A: Not Estimable (CLR325 concentration below lower limit of quantification (LLOQ))	19500000 ng Geometric Coefficient of Variation 125.2	41300000 ng Geometric Coefficient of Variation 253.3	—
Pharmacokinetic of CLR325 and CQJ295: Amount of Drug (or Defined Metabolite) Excreted Into the Urine From Time (Ae 0-28 Hours) CQJ295	NA ng Geometric Coefficient of Variation NA N/A: Not Estimable (CQJ295 concentration below lower limit of quantification (LLOQ))	7620000 ng Geometric Coefficient of Variation 27.2	4040000 ng Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—

SECONDARY outcome

Timeframe: 0-28 hours on Day 1

CLr is the renal clearance from urine following CLR325 infusion. The urine PK parameters were measured using an non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Pharmacokinetic of CLR325 and CQJ295: Renal Clearance From Plasma (CLr) Following Drug Administration CQJ295	NA mL/hr Geometric Coefficient of Variation NA N/A: Not Estimable (CQJ295 concentration below lower limit of quantification (LLOQ))	5620 mL/hr Geometric Coefficient of Variation 71.7	258 mL/hr Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—
Pharmacokinetic of CLR325 and CQJ295: Renal Clearance From Plasma (CLr) Following Drug Administration CLR325	NA mL/hr Geometric Coefficient of Variation NA N/A: Not Estimable (CLR325 concentration below lower limit of quantification (LLOQ))	904 mL/hr Geometric Coefficient of Variation 199.4	411 mL/hr Geometric Coefficient of Variation 395.1	—

SECONDARY outcome

Timeframe: Baseline (BL), Day 10 (D10) and Day 28 (D28)

Population: The Safety population, which consisted of all patients who had been exposed to at least one infusion of study drug or placebo, was considered. Only subjest with or without anitbody detected were included in the analysis.

Anti-CLR325 anti-apelin antibodies in serum were analyzed predose, Day 10 and Day 28 to determine the immunogenicity of an 18-hour i.v. infusion of CLR325 in heart failure patients.

Outcome measures

Outcome measures
Measure	CLR325 0.25 mcg/kg/Min n=4 Participants Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=6 Participants Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo n=10 Participants Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum BL anti-Apelin antibody · Antibody detected = Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum BL anti-Apelin antibody · Antibody detected = No	1 Participants	1 Participants	1 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum BL anti-CLR325 antibody · Antibody detected = Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum BL anti-CLR325 antibody · Antibody detected = No	4 Participants	5 Participants	5 Participants	10 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D10 anti-Apelin antibody · Antibody detected = Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D10 anti-Apelin antibody · Antibody detected = No	0 Participants	0 Participants	1 Participants	1 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D10 anti-CLR325 antibody · Antibody detected = Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D10 anti-CLR325 antibody · Antibody detected = No	3 Participants	4 Participants	6 Participants	7 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D28 anti-Apelin antibody · Antibody detected = Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D28 anti-Apelin antibody · Antibody detected = No	1 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D28 anti-CLR325 antibody · Antibody detected = Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum D28 anti-CLR325 antibody · Antibody detected = No	3 Participants	5 Participants	5 Participants	9 Participants

Adverse Events

CLR325 0.25 mcg/kg/Min

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

CLR325 2.5 mcg/kg/Min

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

CLR325 8 mcg/kg/Min

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CLR325 0.25 mcg/kg/Min n=4 participants at risk Patients randomized to this arm received single dose of CLR325 0.25 mcg/kg/min (i.v.) in double blind manner.	CLR325 2.5 mcg/kg/Min n=6 participants at risk Patients randomized to this arm received single dose of CLR325 2.5 mcg/kg/min (i.v.) in double blind manner.	CLR325 8 mcg/kg/Min n=6 participants at risk Patients randomized to this arm received single dose of CLR325 8 mcg/kg/min (i.v.) in double blind manner.	Placebo n=10 participants at risk Patients randomized to this arm received single dose of Placebo (i.v.) in double blind manner.
Cardiac disorders Acute myocardial infarction	0.00% 0/4 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	16.7% 1/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/10 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.
Cardiac disorders Cardiac failure congestive	0.00% 0/4 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	16.7% 1/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/10 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.
Infections and infestations Bronchitis	0.00% 0/4 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	16.7% 1/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	16.7% 1/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/10 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.
Investigations Hepatic enzyme increased	0.00% 0/4 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	16.7% 1/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/10 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.
Psychiatric disorders Delirium	0.00% 0/4 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	16.7% 1/6 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.	0.00% 0/10 • Adverse Events were collected from first dose of study treatment until end of study treatment plus 30 days post-treatment, up to maximum duration of 1 month. All randomized patients received a single i.v. infusion of CLR325 or placebo for approximately 18 hours. Any sign or symptom that occurs during the study treatment and 30 days post-treatment follow up.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER