Trial Outcomes & Findings for Efficacy and Safety Study of F373280 (NCT NCT01831856)

Last Updated: 2019-07-02

Results Overview

Time to first Atrial Fibrillation (AF) recurrence defined by the first episode of Atrial Fibrillation lasting for at least 10 minutes. AF recurrences or atrial flutter emergences: 7-day continuous electrocardiogram (ECG; 5-leads/2 or 3 channels) ambulatory recording (Holter ECG) between Visit 3 (Electrical Cardioversion Visit) and Visit 4 (Week 5). Then, the follow-up was documented using the Transtelephonic ECG monitor (TTEM): one transmission every two days from Week 9 to Week 24. For randomised patients with spontaneous cardioversion before Electrical Cardioversion, the recurrence of AF or the emergence of atrial flutter was assessed after Visit 3 (from Week 5). Moreover, during this TTEM period, if the patient experienced any AF or atrial flutter symptoms, it was recorded and documented using the TTEM.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

135 participants

Primary outcome timeframe

from electrical cardioversion (Visit 3) to last follow-up visit (W24)

Results posted on

2019-07-02

Participant Flow

It was planned to randomise a total of 152 patients. Due to low recruitment, the study recruitment was interrupted prematurely. Instead of 152 patients, 157 patients were screened and a total of 135 were finally randomised. 1 patient received no dose of the study treatment and was also not included in the analyses.

Patients were randomised after 1 to 4-week run-in period without study treatment.

Participant milestones

Participant milestones
Measure	F373280 1g of F373280: Oral administration, one capsule each evening with dinner.	Placebo Placebo: Oral administration, one capsule each evening with dinner.
Overall Study STARTED	67	67
Overall Study COMPLETED	33	30
Overall Study NOT COMPLETED	34	37

Reasons for withdrawal

Reasons for withdrawal
Measure	F373280 1g of F373280: Oral administration, one capsule each evening with dinner.	Placebo Placebo: Oral administration, one capsule each evening with dinner.
Overall Study Adverse Event	5	8
Overall Study Lack of Efficacy	13	11
Overall Study Unsuccessful Electrical Cardioversion	16	18

Baseline Characteristics

Efficacy and Safety Study of F373280

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	F373280 n=67 Participants 68 patients were randomised in the F373280 arm but one patient did not receive any dose of study treatment. 67 patients were also included in the analyses. 1g of F373280: Oral administration, one capsule each evening with dinner.	Placebo n=67 Participants 67 patients were randomised in the placebo arm. Placebo: Oral administration, one capsule each evening with dinner.	Total n=134 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=93 Participants	33 Participants n=4 Participants	62 Participants n=27 Participants
Age, Categorical >=65 years	38 Participants n=93 Participants	34 Participants n=4 Participants	72 Participants n=27 Participants
Age, Continuous	67.5 years STANDARD_DEVIATION 9.7 • n=93 Participants	65.9 years STANDARD_DEVIATION 10.8 • n=4 Participants	66.7 years STANDARD_DEVIATION 10.3 • n=27 Participants
Sex: Female, Male Female	15 Participants n=93 Participants	16 Participants n=4 Participants	31 Participants n=27 Participants
Sex: Female, Male Male	52 Participants n=93 Participants	51 Participants n=4 Participants	103 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 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	67 Participants n=93 Participants	67 Participants n=4 Participants	134 Participants n=27 Participants
Region of Enrollment Hungary	13 participants n=93 Participants	13 participants n=4 Participants	26 participants n=27 Participants
Region of Enrollment Czechia	18 participants n=93 Participants	15 participants n=4 Participants	33 participants n=27 Participants
Region of Enrollment Poland	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Region of Enrollment Italy	19 participants n=93 Participants	20 participants n=4 Participants	39 participants n=27 Participants
Region of Enrollment Spain	15 participants n=93 Participants	17 participants n=4 Participants	32 participants n=27 Participants
Body Mass Index	28.4 kg/m^2 STANDARD_DEVIATION 4.7 • n=93 Participants	29.1 kg/m^2 STANDARD_DEVIATION 4.9 • n=4 Participants	28.8 kg/m^2 STANDARD_DEVIATION 4.8 • n=27 Participants
Body surface area	1.98 m^2 STANDARD_DEVIATION 0.19 • n=93 Participants	2.02 m^2 STANDARD_DEVIATION 0.19 • n=4 Participants	2.0 m^2 STANDARD_DEVIATION 0.19 • n=27 Participants

PRIMARY outcome

Timeframe: from electrical cardioversion (Visit 3) to last follow-up visit (W24)

Population: The Full Analysis Set is composed of all randomised patients having received at least one dose of the study treatment and with a successful cardioversion observed at Visit 3; a successful cardioversion was defined as either spontaneous cardioversion before Visit 3 or successful Electrical Cardioversion performed at Visit 3.

Outcome measures

Outcome measures
Measure	F373280 n=52 Participants 68 patients were randomised in the F373280 arm but one patient did not receive any dose of study treatment. 67 patients were also included in the analyses. 1g of F373280: Oral administration, one capsule each evening with dinner.	Placebo n=49 Participants 67 patients were randomised in the placebo arm. Placebo: Oral administration, one capsule each evening with dinner.
Time to First Atrial Fibrillation (AF) Recurrence or Atrial Flutter Emergence Defined by the Time to First Episode of AF or Atrial Flutter Lasting for at Least 10 Minutes During the 20-week Follow-up After Visit 3 (Electrical Cardioversion (ECV) Visit).	11.0 days Interval 6.0 to 45.0	16.0 days Interval 6.0 to 141.0

Adverse Events

F373280

Serious events: 5 serious events

Other events: 41 other events

Deaths: 1 deaths

Placebo

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	F373280 n=67 participants at risk 68 patients were randomised in the F373280 arm but one patient did not receive any dose of study treatment. 67 patients were also included in the analyses. 1g of F373280: Oral administration, one capsule each evening with dinner.	Placebo n=67 participants at risk 67 patients were randomised in the placebo arm. Placebo: Oral administration, one capsule each evening with dinner.
Cardiac disorders Ventricular tachycardia	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Gastric ulcer perforation	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Infections and infestations Peritonitis	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Cardiac failure	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Atrial fibrillation	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Cerebrovascular accident	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Pulmonary oedema	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Sick sinus syndrome	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).

Other adverse events

Additional Information

Karim KEDDAD, MD, PhD Head of Medical Unit

Institut de Recherche Pierre Fabre

Phone: +33 5 34 50 61 69

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	F373280 n=67 participants at risk 68 patients were randomised in the F373280 arm but one patient did not receive any dose of study treatment. 67 patients were also included in the analyses. 1g of F373280: Oral administration, one capsule each evening with dinner.	Placebo n=67 participants at risk 67 patients were randomised in the placebo arm. Placebo: Oral administration, one capsule each evening with dinner.
Vascular disorders Orthostatic hypotension	35.8% 24/67 • Number of events 33 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	29.9% 20/67 • Number of events 24 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Vascular disorders Hypertension	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Vascular disorders Hypotension	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Vascular disorders Orthostatic hypertension	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Cardiac failure	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	6.0% 4/67 • Number of events 4 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Cardiac failure congestive	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Intracardiac thrombus	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	7.5% 5/67 • Number of events 5 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Mitral valve incompetence	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Oedema peripheral	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Sinus bradycardia	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Tachyarrhythmia	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Cardiac disorders Ventricular extrasystoles	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Abdominal discomfort	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Abdominal distension	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Diarrhoea	3.0% 2/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Gingival bleeding	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Rectal haemorrhage	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Gastrointestinal disorders Toothache	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Dizziness	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Headache	1.5% 1/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Insomnia	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Partial seizures	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Sciatica	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	3.0% 2/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Nervous system disorders Tremor	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Infections and infestations Gastrointestinal infection	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Infections and infestations Nasopharyngitis	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Infections and infestations Pharyngitis	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Infections and infestations Upper respiratory tract infection	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
General disorders Asthenia	3.0% 2/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
General disorders Fatigue	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
General disorders Non-cardiac chest pain	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Injury, poisoning and procedural complications Limb injury	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Injury, poisoning and procedural complications Overdose	3.0% 2/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Investigations Blood creatinine increased	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Investigations Blood triglycerides increased	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Investigations International normalised ratio decreased	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Investigations International normalised ratio increased	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Eye disorders Glaucoma	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Metabolism and nutrition disorders Hypertriglyceridaemia	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Musculoskeletal and connective tissue disorders Myalgia	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Reproductive system and breast disorders Erectile dysfunction	1.5% 1/67 • Number of events 1 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/67 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).	3.0% 2/67 • Number of events 2 • Adverse events were recorded from the visit 2 to the last visit (Visit 9 Week 24).