Acute Heart FailurePhase 2NCT02002702
Study of Safety, Tolerability and Pharmacokinetics of Serelaxin in Japanese Acute Heart Failure (AHF) Patients
A Phase 2 study testing Serelaxin in people with Acute Heart Failure, run by Novartis Pharmaceuticals at 15 sites in Japan.
Trial summary
This is a multicenter, randomized, double-blind, placebo-controlled study to assess safety, tolerability and pharmacokinetics and to explore efficacy of IV infusion of 10 µg/kg/day and 30 µg/kg/day serelaxin for 48 hours compared to placebo, when added to the standard therapy, in approximately 45 Japanese AHF patients. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Acute Heart Failure
- What is being tested?
- Serelaxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 15 sitesJapan
- Study dates
- Jan 2014to Aug 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any study-specific assessment is performed.
- Male or female ≥20 years of age, with body weight ≥30 kg and ≤160 kg
- Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening:
- Dyspnea at rest or with minimal exertion
- Pulmonary congestion on chest radiograph
- BNP ≥350 pg/mL or NT-proBNP ≥1,400 pg/mL
Show all 10Show fewer
- SBP ≥125 mmHg at the start and at the end of screening
- Able to be randomized within 16 hours from presentation to the hospital, including the emergency department
- Received intravenous (IV) furosemide of at least 40 mg (or equivalent) at any time between presentation (this include outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute heart failure (HF) episode.
- Impaired renal function defined as an estimated glomerular filtration rate (eGFR) between presentation and randomization of ≥ 25 and≤ 75 mL/min/1.73 m2, calculated using the Japanese formula
Who cannot join
- Dyspnea primarily due to non-cardiac causes
- Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
- Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.
- AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate <45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of >130 beats per minute.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Japan15 sites
Novartis Investigative Site
Amagasaki, Hyōgo, 660-8550
Novartis Investigative Site
Fukuoka, Fukuoka, 810-0001
Novartis Investigative Site
Higashiibaraki-gun, Ibaraki, 311-3193
Novartis Investigative Site
Hiroshima, Hiroshima, 730-8518
Novartis Investigative Site
Iizuka, Fukuoka, 820-8505
Novartis Investigative Site
Kanazawa, Ishikawa-ken, 920-8650
Novartis Investigative Site
Kawasaki, Kanagawa, 211-8533
Novartis Investigative Site
Komatsushimachō, Tokushima, 773-8502
Novartis Investigative Site
Osaka, Osaka, 534-0021
Novartis Investigative Site
Sayama, Saitama, 350-1323
Novartis Investigative Site
Sendai, Miyagi, 981-3107
Novartis Investigative Site
Seto, Aichi-ken, 489-8642
Novartis Investigative Site
tabashi City, Tokyo, 173-8610
Novartis Investigative Site
Ueda, Nagano, 386-8610
Novartis Investigative Site
Yokohama, Kanagawa, 231-8682
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Assess the Safety, Tolerability and Pharmacokinetics of Serelaxin When Added to Standard Therapy in Japanese Acute Heart Failure Patients
This is a multicenter, randomized, double-blind, placebo-controlled study to assess safety, tolerability and pharmacokinetics and to explore efficacy of IV infusion of 10 µg/kg/day and 30 µg/kg/day serelaxin for 48 hours compared to placebo, when added to the standard therapy, in approximately 45 Japanese AHF patients.
- Conditions
- Acute Heart Failure
- Being tested
- Serelaxin, Placebo
- Keywords
- Acute heart failure (AHF),, Japanese,, Safety and tolerability, Pharmacokinetics,, Renal Impairment
- Medical subject headings
- Hemophilia A, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SerelaxinDrug
Intravenous infusion
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Serelaxin 10 mcg/kg/Day | Experimental | Participants received 10 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours. Receives: Drug: Serelaxin |
| Serelaxin 30 mcg/kg/Day | Experimental | Participants received 30 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours. Receives: Drug: Serelaxin |
| Placebo | Placebo comparator | Participants received continuous i.v. infusion of placebo matched to serelaxin for 48 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy
AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. AEs leading to discontinuations, or requiring dose adjustment or interruptions and additional therapy were assessed.
Measured: From start of study treatment up to Day 5 (for AEs); From start of study treatment up to Day 14 (for SAEs)
Maximum Plasma Concentration (Cmax) of Serelaxin
Maximum plasma concentration (Cmax) was defined as the peak level of serelaxin, derived from plasma concentration-time data, using a non-compartmental model approach.
Measured: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Weight Adjusted Clearance (CL) of Serelaxin
Weight adjusted clearance (CL) was defined as the total body clearance of serelaxin after drug administration. CL was calculated as nominal infusion rate divided by Css, using a non-compartmental model approach.
Measured: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Concentration at Steady-state (Css) of Serelaxin
Concentration at steady-state (Css) was defined as concentration at the state of equilibrium obtained at the end of a certain number of administrations. Css of serelaxin in plasma was calculated by using a non-compartmental model approach.
Measured: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Secondary outcomes (6)
Change From Baseline in Area Under the Curve (AUC) for Systolic Blood Pressure (SBP) Through 48 Hours of Infusion at Day 5
The area under the curve (AUC) was defined as area under the plasma concentration-time curve from time zero to time of the last time point with measurable concentration, calculated by a trapezoidal method. Systolic blood pressure was measured using a calibrated standard sphygmomanometer after the subject remained in sitting position for 3 minutes at clinic during the visit. Sample collected at: Baseline; 30 \& 60 minutes and then every hour for the first 6 hours of study drug infusion, and then every 3 hours during 48 hours of study drug infusion; every 3 hours until 12 hours following end of infusion, then every 6 hours for 48 hours and then every 24 hours until the earlier of Day 5 or discharge.
AUC for SBP is standardized by dividing by the length of respective time ranges.
Measured: Baseline, 48 hours, Day 5
Change From Baseline in Aldosterone Levels Through Day 14
Aldosterone biomarker was used to assess the effect of serelaxinin on fluid retention. Geometric means of the ratio of post-Baseline values to baseline values of aldosterone was calculated by treatment for the full analysis set.
Measured: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in Cystatin-C Levels Through Day 14
Cystatin-C biomarker was used to assess the effect of serelaxinin on worsening of renal function. Geometric means of the ratio of post-Baseline values to baseline values of Cystatin-C was calculated by treatment for the full analysis set.
Measured: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in High Sensitivity Troponin-T Levels Through Day 14
High sensitivity Troponin-T biomarker was used to assess the effect of serelaxin on myocardial damage. Geometric means of the ratio of post-Baseline values to baseline values of high sensitivity troponin-t was calculated by treatment for the full analysis set.
Measured: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in NT-proBNP Levels Through Day 14
NT-proBNP biomarker was used to assess the effect of serelaxinin on degree of cardiac wall stress and congestion. Geometric means of the ratio of post-Baseline values to baseline values of NT-proBNP was calculated by treatment for the full analysis set.
Measured: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in Neutrophil Gelatinase-asc Lipocalin (NGAL) Levels Through Day 14
Neutrophil gelatinase-asc lipocalin (NGAL) biomarker was used to assess the effect of serelaxin on kidney function. Geometric means of the ratio of post-Baseline values to baseline values of NGAL was calculated by treatment for the full analysis set.
Measured: Baseline, Day 1, Day 2, Day 5, Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2013 (estimated)
- Study startJan 2014
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02002702
- Sponsor's protocol ID
- CRLX030A1201
- Status last verified
- Sep 2015
- First submitted
- 1 Dec 2013
- Last updated
- 12 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Assess the Safety, Tolerability and Pharmacokinetics of Serelaxin When Added to Standard Therapy in Japanese Acute Heart Failure Patients
- ClinicalTrials.gov ID
- NCT02002702
- Acronym / sponsor ID
- CRLX030A1201
- Conditions
- Acute Heart Failure
- Keywords
- Acute heart failure (AHF),, Japanese,, Safety and tolerability, Pharmacokinetics,, Renal Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 6 Dec 2013 (estimated)
- Results
- Posted 12 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, randomized, double-blind, placebo-controlled study to assess safety, tolerability and pharmacokinetics and to explore efficacy of IV infusion of 10 µg/kg/day and 30 µg/kg/day serelaxin for 48 hours compared to placebo, when added to the standard therapy, in approximately 45 Japanese AHF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Serelaxin 10 mcg/kg/Day | Experimental | Drug: SerelaxinParticipants received 10 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours. |
| Serelaxin 30 mcg/kg/Day | Experimental | Drug: SerelaxinParticipants received 30 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received continuous i.v. infusion of placebo matched to serelaxin for 48 hours. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent must be obtained before any study-specific assessment is performed.
- Male or female ≥20 years of age, with body weight ≥30 kg and ≤160 kg
- Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening:
- Dyspnea at rest or with minimal exertion
- Pulmonary congestion on chest radiograph
Key exclusion criteria (4 listed)
- Dyspnea primarily due to non-cardiac causes
- Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
- Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.
- AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate <45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of >130 beats per minute.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SerelaxinIntravenous infusion | Drug | Serelaxin 10 mcg/kg/Day, Serelaxin 30 mcg/kg/Day |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy
Time frame: From start of study treatment up to Day 5 (for AEs); From start of study treatment up to Day 14 (for SAEs)
AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. AEs leading to discontinuations, or requiring dose adjustment or interruptions and additional therapy were assessed.
Maximum Plasma Concentration (Cmax) of Serelaxin
Time frame: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Maximum plasma concentration (Cmax) was defined as the peak level of serelaxin, derived from plasma concentration-time data, using a non-compartmental model approach.
Weight Adjusted Clearance (CL) of Serelaxin
Time frame: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Weight adjusted clearance (CL) was defined as the total body clearance of serelaxin after drug administration. CL was calculated as nominal infusion rate divided by Css, using a non-compartmental model approach.
Concentration at Steady-state (Css) of Serelaxin
Time frame: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Concentration at steady-state (Css) was defined as concentration at the state of equilibrium obtained at the end of a certain number of administrations. Css of serelaxin in plasma was calculated by using a non-compartmental model approach.
6 secondary outcomes
Change From Baseline in Area Under the Curve (AUC) for Systolic Blood Pressure (SBP) Through 48 Hours of Infusion at Day 5
Time frame: Baseline, 48 hours, Day 5
Change From Baseline in Aldosterone Levels Through Day 14
Time frame: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in Cystatin-C Levels Through Day 14
Time frame: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in High Sensitivity Troponin-T Levels Through Day 14
Time frame: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in NT-proBNP Levels Through Day 14
Time frame: Baseline, Day 1, Day 2, Day 5, Day 14
Change From Baseline in Neutrophil Gelatinase-asc Lipocalin (NGAL) Levels Through Day 14
Time frame: Baseline, Day 1, Day 2, Day 5, Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Serelaxin in people with Acute Heart Failure, run by Novartis Pharmaceuticals at 15 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy (time frame: From start of study treatment up to Day 5 (for AEs); From start of study treatment up to Day 14 (for SAEs)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2015.