Trial Outcomes & Findings for A Study of the Efficacy and Safety of Vernakalant Hydrochloride (MK-6621) in Patients With Atrial Fibrillation (MK-6621-010 AM4) (NCT NCT01174160)
NCT ID: NCT01174160
Last Updated: 2015-12-15
Results Overview
The proportion of patients with treatment-induced conversion of atrial fibrillation to sinus rhythm for a minimum duration of 1 minute
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
123 participants
Primary outcome timeframe
Within 90 minutes after first exposure
Results posted on
2015-12-15
Participant Flow
Participant milestones
| Measure |
Vernakalant IV
vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV
|
Placebo
placebo
Up to two 10-min infusions of normal saline
|
|---|---|---|
|
Overall Study
STARTED
|
61
|
62
|
|
Overall Study
Discontinued Pre Dose
|
6
|
6
|
|
Overall Study
Dosed
|
55
|
56
|
|
Overall Study
Discontinued Post Dose
|
2
|
0
|
|
Overall Study
COMPLETED
|
53
|
56
|
|
Overall Study
NOT COMPLETED
|
8
|
6
|
Reasons for withdrawal
| Measure |
Vernakalant IV
vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV
|
Placebo
placebo
Up to two 10-min infusions of normal saline
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Protocol Violation
|
4
|
6
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
A Study of the Efficacy and Safety of Vernakalant Hydrochloride (MK-6621) in Patients With Atrial Fibrillation (MK-6621-010 AM4)
Baseline characteristics by cohort
| Measure |
Vernakalant IV
n=55 Participants
vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV
|
Placebo
n=56 Participants
placebo
Up to two 10-min infusions of normal saline
|
Total
n=111 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.7 years
STANDARD_DEVIATION 13.7 • n=93 Participants
|
59.2 years
STANDARD_DEVIATION 12.0 • n=4 Participants
|
59.9 years
STANDARD_DEVIATION 12.8 • n=27 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
44 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
67 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
54 Participants
n=93 Participants
|
56 Participants
n=4 Participants
|
110 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
55 Participants
n=93 Participants
|
55 Participants
n=4 Participants
|
110 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
Korea, Republic of
|
42 participants
n=93 Participants
|
48 participants
n=4 Participants
|
90 participants
n=27 Participants
|
|
Region of Enrollment
India
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Region of Enrollment
Taiwan
|
13 participants
n=93 Participants
|
7 participants
n=4 Participants
|
20 participants
n=27 Participants
|
|
New York Heart Association (NYHA) Classification
None (no heart failure)
|
50 participants
n=93 Participants
|
53 participants
n=4 Participants
|
103 participants
n=27 Participants
|
|
New York Heart Association (NYHA) Classification
Class I (cardiac disease but no symptoms)
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
New York Heart Association (NYHA) Classification
Class II (mild symptoms during normal activity)
|
2 participants
n=93 Participants
|
2 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
New York Heart Association (NYHA) Classification
Class III (Marked limitation in activity)
|
2 participants
n=93 Participants
|
0 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Structural Heart Disease
None
|
44 participants
n=93 Participants
|
43 participants
n=4 Participants
|
87 participants
n=27 Participants
|
|
Structural Heart Disease
Congestive Heart Failure
|
5 participants
n=93 Participants
|
3 participants
n=4 Participants
|
8 participants
n=27 Participants
|
|
Structural Heart Disease
Ischemic Heart Disease
|
4 participants
n=93 Participants
|
7 participants
n=4 Participants
|
11 participants
n=27 Participants
|
|
Structural Heart Disease
Myocardial Infarction
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Structural Heart Disease
Valvular Heart Disease
|
2 participants
n=93 Participants
|
3 participants
n=4 Participants
|
5 participants
n=27 Participants
|
|
Atrial fibrillation (AF) duration
Less than or equal to 48 hours
|
33 participants
n=93 Participants
|
31 participants
n=4 Participants
|
64 participants
n=27 Participants
|
|
Atrial fibrillation (AF) duration
More than 48 hours
|
22 participants
n=93 Participants
|
25 participants
n=4 Participants
|
47 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Within 90 minutes after first exposureThe proportion of patients with treatment-induced conversion of atrial fibrillation to sinus rhythm for a minimum duration of 1 minute
Outcome measures
| Measure |
Vernakalant IV
n=55 Participants
vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV
|
Placebo
n=56 Participants
placebo
Up to two 10-min infusions of normal saline
|
|---|---|---|
|
Proportion of Patients With Treatment-induced Conversion of Atrial Fibrillation to Sinus Rhythm
|
29 participants
|
7 participants
|
Adverse Events
Vernakalant IV
Serious events: 6 serious events
Other events: 23 other events
Deaths: 0 deaths
Placebo
Serious events: 6 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vernakalant IV
n=55 participants at risk
vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV
|
Placebo
n=56 participants at risk
placebo
Up to two 10-min infusions of normal saline
|
|---|---|---|
|
Cardiac disorders
Arrhythmia
|
1.8%
1/55
|
0.00%
0/56
|
|
Cardiac disorders
Congestive Heart Failure
|
0.00%
0/55
|
1.8%
1/56
|
|
Cardiac disorders
Sick sinus syndrome
|
1.8%
1/55
|
0.00%
0/56
|
|
General disorders
Chest pain
|
0.00%
0/55
|
3.6%
2/56
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/55
|
3.6%
2/56
|
|
Nervous system disorders
Dizziness
|
0.00%
0/55
|
1.8%
1/56
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.6%
2/55
|
0.00%
0/56
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/55
|
1.8%
1/56
|
|
Investigations
Prothrombin time prolonged
|
0.00%
0/55
|
1.8%
1/56
|
|
Renal and urinary disorders
Acute renal failure
|
1.8%
1/55
|
0.00%
0/56
|
|
Vascular disorders
Neurogenic shock
|
1.8%
1/55
|
0.00%
0/56
|
Other adverse events
| Measure |
Vernakalant IV
n=55 participants at risk
vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV
|
Placebo
n=56 participants at risk
placebo
Up to two 10-min infusions of normal saline
|
|---|---|---|
|
Cardiac disorders
Bradycardia
|
7.3%
4/55
|
3.6%
2/56
|
|
Cardiac disorders
Ventricular tachycardia
|
1.8%
1/55
|
7.1%
4/56
|
|
Cardiac disorders
Sick sinus syndrom
|
3.6%
2/55
|
0.00%
0/56
|
|
Cardiac disorders
Hypertensive heart disease
|
1.8%
1/55
|
0.00%
0/56
|
|
Cardiac disorders
Palpitations
|
1.8%
1/55
|
0.00%
0/56
|
|
Cardiac disorders
Sinus arrest
|
1.8%
1/55
|
0.00%
0/56
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/55
|
1.8%
1/56
|
|
General disorders
Chest discomfort
|
1.8%
1/55
|
1.8%
1/56
|
|
General disorders
Pyrexia
|
1.8%
1/55
|
1.8%
1/56
|
|
General disorders
Asthenia
|
0.00%
0/55
|
1.8%
1/56
|
|
General disorders
Chills
|
1.8%
1/55
|
0.00%
0/56
|
|
General disorders
Generalised oedema
|
0.00%
0/55
|
1.8%
1/56
|
|
General disorders
Pain
|
1.8%
1/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/55
|
3.6%
2/56
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/55
|
3.6%
2/56
|
|
Gastrointestinal disorders
Nausea
|
1.8%
1/55
|
1.8%
1/56
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/55
|
1.8%
1/56
|
|
Gastrointestinal disorders
Dyspepsia
|
1.8%
1/55
|
0.00%
0/56
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/55
|
1.8%
1/56
|
|
Gastrointestinal disorders
Intestinal polyp
|
0.00%
0/55
|
1.8%
1/56
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/55
|
1.8%
1/56
|
|
Nervous system disorders
Dysgeusia
|
1.8%
1/55
|
1.8%
1/56
|
|
Nervous system disorders
Dizziness
|
1.8%
1/55
|
3.6%
2/56
|
|
Nervous system disorders
Headache
|
1.8%
1/55
|
0.00%
0/56
|
|
Nervous system disorders
Paraesthesia
|
1.8%
1/55
|
0.00%
0/56
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.6%
2/55
|
1.8%
1/56
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
7.3%
4/55
|
0.00%
0/56
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
1.8%
1/55
|
0.00%
0/56
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/55
|
1.8%
1/56
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
1.8%
1/55
|
0.00%
0/56
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.6%
2/55
|
0.00%
0/56
|
|
Vascular disorders
Hypotension
|
0.00%
0/55
|
5.4%
3/56
|
|
Vascular disorders
Hypertension
|
0.00%
0/55
|
1.8%
1/56
|
|
Infections and infestations
Nasopharyngitis
|
3.6%
2/55
|
0.00%
0/56
|
|
Infections and infestations
Pneumonia
|
1.8%
1/55
|
0.00%
0/56
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
1.8%
1/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/55
|
1.8%
1/56
|
|
Injury, poisoning and procedural complications
Wound complications
|
1.8%
1/55
|
0.00%
0/56
|
|
Investigations
Alanine aminotransferase increased
|
3.6%
2/55
|
0.00%
0/56
|
|
Investigations
Aspartate aminotransferase increased
|
3.6%
2/55
|
0.00%
0/56
|
|
Investigations
Weight decreased
|
0.00%
0/55
|
1.8%
1/56
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.8%
1/55
|
5.4%
3/56
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/55
|
1.8%
1/56
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
0.00%
0/55
|
1.8%
1/56
|
|
Psychiatric disorders
Anxiety disorder
|
1.8%
1/55
|
0.00%
0/56
|
|
Psychiatric disorders
Insomnia
|
1.8%
1/55
|
0.00%
0/56
|
|
Psychiatric disorders
Panic attack
|
1.8%
1/55
|
0.00%
0/56
|
|
Renal and urinary disorders
Acute renal failure
|
3.6%
2/55
|
0.00%
0/56
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.8%
1/55
|
0.00%
0/56
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/55
|
1.8%
1/56
|
|
Blood and lymphatic system disorders
Bicytopenia
|
1.8%
1/55
|
0.00%
0/56
|
|
Ear and labyrinth disorders
Tinnitus
|
1.8%
1/55
|
0.00%
0/56
|
|
Eye disorders
Lacrimation increased
|
1.8%
1/55
|
0.00%
0/56
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/55
|
1.8%
1/56
|
Additional Information
Jonathan Mather, Director, Head of Regulatory Affairs
Cardiome Pharma
Phone: +44 (0)7581148916
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The PI agrees to submit a copy of a 'Publication' to CRO/Sponsor for review and comment 60 days prior to submission for publication and / or disclosure. Sponsor has the applicable 60 day period to respond to PI with any requested revisions. PI agrees to delete any confidential information (excluding results) identified by Sponsor as confidential prior to submitting/presenting the publication.
- Publication restrictions are in place
Restriction type: OTHER