Atrial FibrillationPhase 2NCT04582409
A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation
A Phase 2 study testing HSY244 in people with Atrial Fibrillation, run by Novartis Pharmaceuticals at 4 sites in 2 countries.
Trial summary
This was a randomized, placebo-controlled, investigator- and participant-blinded study to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of HSY244 in participants with atrial fibrillation (AF), with and without heart failure (HF). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- HSY244
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 30 Nov 2020to 11 Jul 2022
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At screening, written informed consent were required to be obtained before any assessment was performed and only participants able to provide written informed consent themselves were included in this study.
- Hemodynamically stable men and women (either of non-child-bearing potential or child bearing potential with highly effective contraception) between 18 and 80 years of age (inclusive) at screening with a clinical indication for direct current cardioversion of AF.
- At screening, current episode of AF had been ongoing for ≥6 hours and ≤60 days
- Successful initiation and achievement of therapeutic levels of national guideline and institution-specific anticoagulation therapy as appropriate for the duration of the AF episode and risk for the participant.
- Completion of national guideline and institution-specific imaging evaluation for left atrial thrombi as appropriate for the duration of AF episode and risk for the participant.
- At screening, participants were required to weigh at least 60 kg to participate in the study and were required to have a body mass index (BMI) within the range of 18 - 45 kg/m^2. BMI = Body weight (kg) / [Height (m)]^2
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- At screening, vital signs (systolic blood pressure and pulse rate) were assessed in the sitting position. Sitting vital signs were required to be within the following ranges (exclusive):
- systolic blood pressure between 100-160 mmHg and diastolic blood pressure 60-100 mmHg
- pulse rate (ventricular rate) between 60-120 bpm.
Who cannot join
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 4 days after stopping of investigational drug.
- Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 96 hours after study drug administration. A condom was required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner. In addition, male participants could not donate sperm for the time period specified above.
- Use of any anti-arrhythmic class I or III drug (including Ranolazine [Ranexa]) within 5 half lives before randomization; including use of amiodarone within 3 months before randomization.
- At screening, history of current diagnosis of ECG abnormalities or cardiac rhythm disorders as determined by the Investigator's interpretation of the ECG findings indicating a significant risk for participating in the study, such as:
- History of Torsades de Pointes (TdP), any other polymorphic ventricular tachycardia, sustained monomorphic ventricular tachycardia, long QT syndrome, or Brugada syndrome.
- Wolfe-Parkinson-White (WPW) syndrome
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- In the absence of a complete bundle branch block a resting QTcF >460 msec for men and >470 msec for women (mean of ≥ 5 consecutive QT intervals)
- In the presence of a complete bundle branch block, a prolonged QTcF or JTc that, in the opinion of the investigator, may pose a risk to patient safety
- Third-degree (complete) heart block, or second-degree Mobitz type II heart block
- Attempted or unsuccessful cardioversion within 2 weeks prior to randomization.
- Presence of known severe mitral regurgitation and/or known severely dilated left atrium.
- Pre-existing or tachycardia-induced moderate to severe cardiac dysfunction (New York Heart Association Class III and IV).
- History within the preceding 3 months prior to randomization of: myocardial infarction, unstable angina, cardiac surgery, or a percutaneous coronary intervention.
- History of a confirmed stroke or transient ischemic attack (TIA).
- History or current diagnosis of any seizure disorder, epilepsy, significant head trauma, or other disorders increasing the risk for seizures.
- History or current diagnosis of a major neurologic or psychiatric disorder that, in the opinion of the investigator, poses a risk to patient safety to participate.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States2 sites
Novartis Investigative Site
Boston, Massachusetts, 02215
Novartis Investigative Site
Lansing, Michigan, 48912
Germany2 sites
Novartis Investigative Site
Bad Oeynhausen, 32545
Novartis Investigative Site
Frankfurt, 60590
About this study
Official title: A Randomized, Placebo-controlled, Investigator- and Participant-blinded Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation
This was a randomized, placebo-controlled, investigator- and participant-blinded study to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of HSY244 in participants with atrial fibrillation (AF), with and without heart failure (HF).
Read the detailed description
A screening period of up to 3 days (72 hours) was used to assess eligibility. After eligibility was confirmed, patients were randomized to either HSY244 or placebo. Prior to study drug administration, pre-dose assessments were completed. After the start of study drug administration, the participant was monitored for cardioversion to sinus rhythm. If a participant was still in AF at 90 minutes after the start of study drug administration, direct current cardioversion was planned to be applied at a time deemed appropriate by the investigator.
- Conditions
- Atrial Fibrillation
- Being tested
- HSY244, Placebo
- Keywords
- atrial fibrillation, arrhythmia, pharmacological cardioversion
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSY244Drug
HSY244 concentrate solution for injection via intravenous infusion
PlaceboOther
Placebo concentrate solution for injection via intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| HSY244 | Experimental | HSY244 150 mg concentrate solution for injection via intravenous infusion Receives: Drug: HSY244 |
| Placebo | Placebo comparator | Placebo concentrate solution for injection via intravenous infusion Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Conversion to Sinus Rhythm for at Least 1 Minute Within 90 Minutes From the Start of Study Drug Administration.
Conversion to sinus rhythm was monitored using a Holter monitoring device through 90 minutes after the start of study drug administration.
If a participant had been monitored for at least 45 minutes and did not convert to sinus rhythm for at least one minute, the primary endpoint was defined as 'no'. If a participant converted to sinus rhythm for at least one minute at any time during the post-treatment 90 minutes observation period, regardless of the length of time monitored, the primary endpoint was to be defined as 'yes'.
Measured: 90 minutes from the start of study drug administration
Secondary outcomes (3)
Maximum Observed Plasma Concentration (Cmax)
The Cmax is the maximum (peak) observed plasma drug concentration after single-dose administration.
Actual recorded sampling times were taken into consideration for PK calculations.
Measured: Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5
Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time).
Actual recorded sampling times were taken into consideration for PK calculations.
Measured: Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5
Area Under the Plasma Concentration-time Curve (AUClast)
AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast).
Actual recorded sampling times were taken into consideration for PK calculations.
Measured: Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start30 Nov 2020
- Primary completion11 Jul 2022
- Study completion11 Jul 2022
Why it stopped: Terminated due to business decision
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 Atrial FibrillationStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 13 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
- NCT04582409
- Sponsor's protocol ID
- CHSY244X2201
- Other IDs
- 2020-004327-17
- Status last verified
- Jun 2024
- First submitted
- 7 Oct 2020
- Last updated
- 20 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Investigator- and Participant-blinded Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT04582409
- Acronym / sponsor ID
- CHSY244X2201
- Conditions
- Atrial Fibrillation
- Keywords
- atrial fibrillation, arrhythmia, pharmacological cardioversion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to business decision
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 11 Jul 2022 (actual)
- Study completion
- 11 Jul 2022 (actual)
- First posted
- 9 Oct 2020 (actual)
- Results
- Posted 25 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a randomized, placebo-controlled, investigator- and participant-blinded study to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of HSY244 in participants with atrial fibrillation (AF), with and without heart failure (HF).
Detailed description
A screening period of up to 3 days (72 hours) was used to assess eligibility. After eligibility was confirmed, patients were randomized to either HSY244 or placebo. Prior to study drug administration, pre-dose assessments were completed. After the start of study drug administration, the participant was monitored for cardioversion to sinus rhythm. If a participant was still in AF at 90 minutes after the start of study drug administration, direct current cardioversion was planned to be applied at a time deemed appropriate by the investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HSY244 | Experimental | Drug: HSY244HSY244 150 mg concentrate solution for injection via intravenous infusion |
| Placebo | Placebo comparator | Other: PlaceboPlacebo concentrate solution for injection via intravenous infusion |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- At screening, written informed consent were required to be obtained before any assessment was performed and only participants able to provide written informed consent themselves were included in this study.
- Hemodynamically stable men and women (either of non-child-bearing potential or child bearing potential with highly effective contraception) between 18 and 80 years of age (inclusive) at screening with a clinical indication for direct current cardioversion of AF.
- At screening, current episode of AF had been ongoing for ≥6 hours and ≤60 days
- Successful initiation and achievement of therapeutic levels of national guideline and institution-specific anticoagulation therapy as appropriate for the duration of the AF episode and risk for the participant.
- Completion of national guideline and institution-specific imaging evaluation for left atrial thrombi as appropriate for the duration of AF episode and risk for the participant.
Key exclusion criteria (16 listed)
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 4 days after stopping of investigational drug.
- Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 96 hours after study drug administration. A condom was required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner. In addition, male participants could not donate sperm for the time period specified above.
- Use of any anti-arrhythmic class I or III drug (including Ranolazine [Ranexa]) within 5 half lives before randomization; including use of amiodarone within 3 months before randomization.
- At screening, history of current diagnosis of ECG abnormalities or cardiac rhythm disorders as determined by the Investigator's interpretation of the ECG findings indicating a significant risk for participating in the study, such as:
- Attempted or unsuccessful cardioversion within 2 weeks prior to randomization.
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 |
|---|---|---|
| HSY244HSY244 concentrate solution for injection via intravenous infusion | Drug | HSY244 |
| PlaceboPlacebo concentrate solution for injection via intravenous infusion | Other | Placebo |
Primary outcome
Number of Participants With Conversion to Sinus Rhythm for at Least 1 Minute Within 90 Minutes From the Start of Study Drug Administration.
Time frame: 90 minutes from the start of study drug administration
Conversion to sinus rhythm was monitored using a Holter monitoring device through 90 minutes after the start of study drug administration. If a participant had been monitored for at least 45 minutes and did not convert to sinus rhythm for at least one minute, the primary endpoint was defined as 'no'. If a participant converted to sinus rhythm for at least one minute at any time during the post-treatment 90 minutes observation period, regardless of the length of time monitored, the primary endpoint was to be defined as 'yes'.
3 secondary outcomes
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5
Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Time frame: Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5
Area Under the Plasma Concentration-time Curve (AUClast)
Time frame: Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results for CHSY244X2201 that is getting linked from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- Patient Lay Trial SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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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
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HSY244 in people with Atrial Fibrillation, run by Novartis Pharmaceuticals at 4 sites in 2 countries.
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 9 inclusion and 16 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: stopped early, as of the sponsor's last update on 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Germany. 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 25 Jul 2023). 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 Conversion to Sinus Rhythm for at Least 1 Minute Within 90 Minutes From the Start of Study Drug Administration. (time frame: 90 minutes from the start of study drug administration). 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 20 Jun 2024.