Atrial FibrillationPhase 2NCT04571385
A Study Evaluating the Efficacy and Safety of AP30663 for Cardioversion in Participants With Atrial Fibrillation (AF)
A Phase 2 study testing AP30663 in people with Atrial Fibrillation, run by Acesion Pharma at 15 sites in 2 countries.
Trial summary
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of one or more doses of AP30663 for cardioversion in adult participants with AF. 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?
- AP30663
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 9 Sep 2019to 23 Jan 2023
- 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
- Clinical indication for cardioversion of AF
- Current episode of symptomatic AF lasting between 3-hour and 7 days (inclusive) at randomization
- Adequate anticoagulation according to international and/or national guidelines
Who cannot join
- Significant clinical illness or surgical procedure within 4 weeks preceding the screening visit
- History of significant mental, renal or hepatic disorder, chronic obstructive pulmonary disease, sinus nodal disease, or other significant disease, as judged by the investigator.
- Any cardioversion attempt of AF or atrial flutter within 4 weeks preceding randomization
- Use of any antiarrhythmic drug class I and/or III within 6 months before randomisation
- Other protocol defined Inclusion/Exclusion criteria may apply
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
Hungary10 sites
Acesion Pharma Investigational Site 202
Budapest
Acesion Pharma Investigational Site 203
Budapest
Acesion Pharma Investigational Site 207
Budapest
Acesion Pharma Investigational Site 212
Budapest
Acesion Pharma Investigational Site 213
Budapest
Acesion Pharma Investigational Site 214
Budapest
Acesion Pharma Investigational Site 211
Pécs
Acesion Pharma Investigational Site 201
Szekszárd
Acesion Pharma Investigational Site 210
Szentes
Acesion Pharma Investigational Site 204
Zalaegerszeg
Denmark5 sites
Acesion Pharma Investigational Site 110
Aalborg
Acesion Pharma Investigational Site 106
Copenhagen
Acesion Pharma Investigational Site 108
Hellerup
Acesion Pharma Investigational Site 113
Hillerød
Acesion Pharma Investigational Site 105
Roskilde
About this study
Official title: A Double-Blind, Randomised, Placebo-Controlled, Parallel-Group Study of AP30663 Given Intravenously for Cardioversion in Patients With Atrial Fibrillation
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of one or more doses of AP30663 for cardioversion in adult participants with AF.
- Conditions
- Atrial Fibrillation
- Being tested
- AP30663, Placebo
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP30663Drug
Administer by intravenous infusion.
PlaceboDrug
Placebo matched to AP30663.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: AP30663 | Experimental | Participants will receive single dose of AP30663. Receives: Drug: AP30663 |
| Part 1: Placebo | Placebo comparator | Participants will receive placebo matched to AP30663. Receives: Drug: Placebo |
| Part 2: AP30663 | Experimental | Participants will receive a single dose of one of the multiple dose levels of AP30663. Receives: Drug: AP30663 |
| Part 2: Placebo | Placebo comparator | Participants will receive placebo matched to AP30663. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Converted From Atrial Fibrillation (AF) Within 90 Minutes From Start of Infusion and Subsequently Had no AF Recurrence Within 1 Minute of Conversion From AF
The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. Electrocardiogram (ECG) was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Conversion from AF to normal sinus rhythm within 90 minutes from start of infusion was determined by the investigator and documented with a rhythm strip confirming conversion. Percentages were based on "number of participants converted from atrial fibrillation and absence of recurrence of AF within 1 minute of conversion" divided by "total number of participants" *100 in each treatment group. Analysis was performed based on Bayesian model.
Measured: Within 90 minutes from the start of infusion (Day 1)
Secondary outcomes (12)
Time to Conversion From Atrial Fibrillation From Start of Infusion
The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. ECG was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Time to conversion (in minutes) was calculated by time of conversion or censoring minus time of start of infusion.
Measured: From start of infusion (Day 1) up to Day 2
Percentage of Participants With Relapse of AF Within 5 Minutes (IRAF) After Pharmacological or Direct Current (DC) Cardioversion
The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. ECG was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Participants with relapse of AF within 5 minutes following pharmacological or DC cardioversion was presented by treatment and analyzed using a logistic regression model. Percentages were based on "number of participants with relapse of AF within 5 minutes after Pharmacological or DC cardioversion" divided by "total number of participants" *100 in each treatment group.
Measured: Within 5 minutes after cardioversion (Day 1)
Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion
The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. ECG was performed in a standardized manner that the participant had rested in the semi-supine position for at least 5 minutes. Percentage of participants in SR was assessed from Holter ECGs at 3 hours, 24 hours and Day 30 after start of infusion. Percentages were based on "number of participants in SR at 3 hours, 24 hours and Day 30 after start of infusion" divided by "total number of participants" *100 in each treatment group.
Measured: At 3 hours, 24 hours and Day 30 after start of Infusion (Day 1)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. TEAEs are defined as any AE occurring or worsening on or after the first dose of study medication. A serious adverse event (SAE) is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. TEAEs include both serious and non-serious adverse events.
Measured: From start of infusion (Day 1) up to follow-up (Day 35)
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time
QTcF was assessed based on 12-lead Holter monitoring equipment. Triplicate ECGs were extracted at the same time points as PK sampling and were read in a semi-automated manner by a blinded cardiologist. The participant rested in the semi-supine position for at least 5 minutes at ECG extraction timepoints. Change from baseline was estimated based on a linear mixed-effects model: ΔQTcF = Time + Treatment + Time*Treatment + Baseline QTcF.
Measured: Baseline, 15 minutes, 45 minutes, 2 hours, 8 hours and 24 hours post-dose
Maximum Observed Peak Plasma Concentration (Cmax) of AP30663
Cmax was defined as the maximum observed peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Blood samples were collected at indicated timepoints. Pharmacokinetics (PK) was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Time to Reach Peak Plasma Concentration (Tmax) of AP30663
Tmax was directly determined from concentration time data. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Terminal Half Life of (T1/2) of AP30663
T1/2 was calculated as loge (2) per elimination rate constant (kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Area Under the Concentration Time Curve From Pre-dose Concentration up to 30 Minutes (AUC0-0.5) of AP30663
AUC0-0.5 was defined as area under the concentration time curve from pre-dose concentration up to 30 minutes. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30 minutes post-infusion
Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUC0-t) of AP30663
AUC0-t was defined as area under the concentration-time curve from time zero to time of last measurable concentration. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Area Under the Concentration-Time Curve From Pre-dose (Zero) Through Concentration to Infinity (AUC0-inf) of AP30663
AUC0-inf was defined as area under the concentration time curve from pre-dose through concentration to infinity (extrapolated), calculated as AUC0-t + Ct/Kel, where Ct is the last observed non-zero concentration. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Elimination Rate Constant (Kel) of AP30663
Kel represents the fraction of drug eliminated per unit of time. Elimination rate constant was calculated using linear regression on the terminal portion of the log-linear concentration versus time curve. Blood samples were collected at indicated timepoints. Pharmacokinetics was conducted using standard noncompartmental method.
Measured: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2020
- Study start9 Sep 2019
- Primary completion13 Dec 2022
- Study completion23 Jan 2023
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- 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
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acesion Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04571385
- Sponsor's protocol ID
- AP30663-2001
- Other IDs
- 2018-004445-17, 2018
- Status last verified
- Nov 2023
- First submitted
- 25 Sep 2020
- Last updated
- 6 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Holst AG, Tomcsanyi J, Vestbjerg B, Grunnet M, Sorensen US, Diness JG, Bentzen BH, Edvardsson N, Hohnloser SH, Bhatt DL, Dorian P. Inhibition of the KCa2 potassium channel in atrial fibrillation: a randomized phase 2 trial. Nat Med. 2024 Jan;30(1):106-111. doi: 10.1038/s41591-023-02679-9. Epub 2023 Dec 13.
PubMed 38092897
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomised, Placebo-Controlled, Parallel-Group Study of AP30663 Given Intravenously for Cardioversion in Patients With Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT04571385
- Acronym / sponsor ID
- AP30663-2001
- Conditions
- Atrial Fibrillation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Acesion PharmaIndustry (pharma, biotech, devices)
- Study start
- 9 Sep 2019 (actual)
- Primary completion
- 13 Dec 2022 (actual)
- Study completion
- 23 Jan 2023 (actual)
- First posted
- 1 Oct 2020 (actual)
- Results
- Posted 6 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of one or more doses of AP30663 for cardioversion in adult participants with AF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: AP30663 | Experimental | Drug: AP30663Participants will receive single dose of AP30663. |
| Part 1: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matched to AP30663. |
| Part 2: AP30663 | Experimental | Drug: AP30663Participants will receive a single dose of one of the multiple dose levels of AP30663. |
| Part 2: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matched to AP30663. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Clinical indication for cardioversion of AF
- Current episode of symptomatic AF lasting between 3-hour and 7 days (inclusive) at randomization
- Adequate anticoagulation according to international and/or national guidelines
Key exclusion criteria (5 listed)
- Significant clinical illness or surgical procedure within 4 weeks preceding the screening visit
- History of significant mental, renal or hepatic disorder, chronic obstructive pulmonary disease, sinus nodal disease, or other significant disease, as judged by the investigator.
- Any cardioversion attempt of AF or atrial flutter within 4 weeks preceding randomization
- Use of any antiarrhythmic drug class I and/or III within 6 months before randomisation
- Other protocol defined Inclusion/Exclusion criteria may apply
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 |
|---|---|---|
| AP30663Administer by intravenous infusion. | Drug | Part 1: AP30663, Part 2: AP30663 |
| PlaceboPlacebo matched to AP30663. | Drug | Part 1: Placebo, Part 2: Placebo |
Primary outcome
Percentage of Participants Who Converted From Atrial Fibrillation (AF) Within 90 Minutes From Start of Infusion and Subsequently Had no AF Recurrence Within 1 Minute of Conversion From AF
Time frame: Within 90 minutes from the start of infusion (Day 1)
The 12-lead Holter monitoring equipment was used to monitor heart rate and its rhythm. Electrocardiogram (ECG) was performed in a standardized manner after the participant had rested in the semi-supine position for at least 5 minutes. Conversion from AF to normal sinus rhythm within 90 minutes from start of infusion was determined by the investigator and documented with a rhythm strip confirming conversion. Percentages were based on "number of participants converted from atrial fibrillation and absence of recurrence of AF within 1 minute of conversion" divided by "total number of participants" *100 in each treatment group. Analysis was performed based on Bayesian model.
12 secondary outcomes
Time to Conversion From Atrial Fibrillation From Start of Infusion
Time frame: From start of infusion (Day 1) up to Day 2
Percentage of Participants With Relapse of AF Within 5 Minutes (IRAF) After Pharmacological or Direct Current (DC) Cardioversion
Time frame: Within 5 minutes after cardioversion (Day 1)
Percentage of Participants With Sinus Rhythm (SR) at 3 Hours, 24 Hours and Day 30 After Start of Infusion
Time frame: At 3 hours, 24 hours and Day 30 after start of Infusion (Day 1)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From start of infusion (Day 1) up to follow-up (Day 35)
Changes From Baseline in Fridericia's Correction of QT Interval (ΔQTcF) Interval Data Over Time
Time frame: Baseline, 15 minutes, 45 minutes, 2 hours, 8 hours and 24 hours post-dose
Maximum Observed Peak Plasma Concentration (Cmax) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Time to Reach Peak Plasma Concentration (Tmax) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Terminal Half Life of (T1/2) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Area Under the Concentration Time Curve From Pre-dose Concentration up to 30 Minutes (AUC0-0.5) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30 minutes post-infusion
Area Under the Concentration Time Curve up to the Last Measurable Concentration (AUC0-t) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Area Under the Concentration-Time Curve From Pre-dose (Zero) Through Concentration to Infinity (AUC0-inf) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Elimination Rate Constant (Kel) of AP30663
Time frame: Baseline (pre-infusion) and at 5, 15, 25, 30, 45 minutes, 1 hour, 1.5 hours, 4 hours, 8 hours and 24 hours post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38092897Holst AG, Tomcsanyi J, Vestbjerg B, Grunnet M, Sorensen US, Diness JG, Bentzen BH, Edvardsson N, Hohnloser SH, Bhatt DL, Dorian P. Inhibition of the KCa2 potassium channel in atrial fibrillation: a randomized phase 2 trial. Nat Med. 2024 Jan;30(1):106-111. doi: 10.1038/s41591-023-02679-9. Epub 2023 Dec 13.
- Individual participant dataSharing planned: No
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Atrial Fibrillation (AF)
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.
The record lists no contact. Use the official record to reach the sponsor.
15 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 AP30663 in people with Atrial Fibrillation, run by Acesion Pharma at 15 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 3 inclusion and 5 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 6 May 2024. 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 Hungary, Denmark. 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 6 May 2024). 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?
Percentage of Participants Who Converted From Atrial Fibrillation (AF) Within 90 Minutes From Start of Infusion and Subsequently Had no AF Recurrence Within 1 Minute of Conversion From AF (time frame: Within 90 minutes from the start of infusion (Day 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04571385, which also lists 1 linked publication.
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 6 May 2024.