Trial Outcomes & Findings for Evaluation of Long-term Safety, and Efficacy of Brivaracetam (BRV) Used as Adjunctive Treatment in Subjects With Epilepsy (NCT NCT01728077)

Last Updated: 2018-07-11

Results Overview

TEAEs were defined as AEs that had onset on or after the day of first study medication dose. An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Results are presented as the percentage of subjects with at least one treatment-emergent adverse event during this study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

26 participants

Primary outcome timeframe

From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)

Results posted on

2018-07-11

Participant Flow

This study started to enroll subjects in October 2012 and concluded in August 2016.

Participant Flow refers to the Safety Set (SS), which consisted of all subjects who took at least 1 dose of study drug.

Participant milestones

Participant milestones
Measure	Brivaracetam Focal Epilepsy This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day.	Brivaracetam Generalized Epilepsy This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day.
Overall Study STARTED	19	7
Overall Study COMPLETED	11	2
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Brivaracetam Focal Epilepsy This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day.	Brivaracetam Generalized Epilepsy This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day.
Overall Study Lack of Efficacy	3	1
Overall Study Lost to Follow-up	1	0
Overall Study Subject choice	2	3
Overall Study Death	0	1
Overall Study Patient moving	1	0
Overall Study Non compliance	1	0

Baseline Characteristics

Evaluation of Long-term Safety, and Efficacy of Brivaracetam (BRV) Used as Adjunctive Treatment in Subjects With Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brivaracetam Focal Epilepsy n=19 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day.	Brivaracetam Generalized Epilepsy n=7 Participants This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day.	Total Title n=26 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	7 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous Arithmetic mean (standard deviation)	38.6 years STANDARD_DEVIATION 10.9 • n=5 Participants	30.7 years STANDARD_DEVIATION 13.2 • n=7 Participants	36.5 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)

Outcome measures

Outcome measures
Measure	Brivaracetam Focal Epilepsy (SS) n=19 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) n=7 Participants This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Incidence of Treatment Emergent Adverse Events (TEAEs) During Evaluation Period	78.9 percentage of subjects	71.4 percentage of subjects

PRIMARY outcome

Timeframe: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)

An AE was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. Results are presented as the percentage of subjects withdrawn due to an AE.

Outcome measures

Outcome measures
Measure	Brivaracetam Focal Epilepsy (SS) n=19 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) n=7 Participants This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Percentage of Subjects Withdrawn Due to an Adverse Event (AE) During the Evaluation Period	0 percentage of subjects	14.3 percentage of subjects

PRIMARY outcome

Timeframe: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)

Population: The analysis was performed on the Safety Set (SS), which consisted of all subjects who took at least 1 dose of study drug.

SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity or are a congenital anomaly/birth defects. Results are presented as the percentage of subjects with at least one SAE during this study.

Outcome measures

Outcome measures
Measure	Brivaracetam Focal Epilepsy (SS) n=19 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) n=7 Participants This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Occurrence of a Serious Adverse Event (SAE) During the Evaluation Period	26.3 percentage of subjects	28.6 percentage of subjects

SECONDARY outcome

Timeframe: From Entry Visit (Month 0) to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 46 months)

Population: The analysis was performed on the Efficacy Analysis Set (EAS), which consisted of subjects who took at least one dose of study drug and had at least one seizure daily record card (DRC) day during the Evaluation Period.

The POS frequency is standardized to a 28-day duration. Results are presented as the median number of seizures per 28 days.

Outcome measures

Outcome measures
Measure	Brivaracetam Focal Epilepsy (SS) n=17 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Frequency of Partial-Onset Seizure (POS) Type I Per 28 Days During the Evaluation Period for Subjects With Focal-onset Epilepsy	0.4 Seizures per 28 days Interval 0.0 to 124.0	—

SECONDARY outcome

Timeframe: From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months)

The POS frequency is standardized to a 28-day duration. Results are presented as the median percentage of reduction per 28 days. Negative values indicate improvement from Baseline.

Outcome measures

Outcome measures
Measure	Brivaracetam Focal Epilepsy (SS) n=17 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Percentage of Change in Partial-Onset-Seizure (POS) Type I Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected	-56.3 percentage of change Interval -97.0 to 717.0	—

SECONDARY outcome

Timeframe: From Baseline of the previous study to the Last Evaluation Period Visit or Early Discontinuation Visit (up to 49 months)

The POS frequency is standardized to a 28-day duration. A responder is defined as a subject with a \>=50% reduction in seizure frequency from the Baseline Period of the previous study. Results are presented as the percentage of subjects with 50 % responder rate in POS Type I frequency.

Outcome measures

Outcome measures
Measure	Brivaracetam Focal Epilepsy (SS) n=17 Participants This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
50 % Responder Rate in Partial-Onset-Seizure (POS) Type I Frequency From Baseline of the Previous Study to the Evaluation Period for Subjects With Focal-onset Epilepsy Entering N01372 From a Study Where Baseline Seizure Data Was Collected	54.5 percentage of subjects	—

Adverse Events

Brivaracetam Focal Epilepsy (SS)

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Brivaracetam Generalized Epilepsy (SS)

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

UCB

Cares

Phone: +1844599

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Brivaracetam Focal Epilepsy (SS) n=19 participants at risk This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) n=7 participants at risk This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Blood and lymphatic system disorders Leukocytosis	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/19 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Cardiac disorders Myocardial infarction	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
General disorders Chest pain	5.3% 1/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
General disorders Drowning	0.00% 0/19 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Pneumonia	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Sepsis	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Metabolism and nutrition disorders Hypomagnesaemia	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Nervous system disorders Convulsion	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Nervous system disorders Status epilepticus	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Psychiatric disorders Conversion disorder	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Vascular disorders Hypertension	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Vascular disorders Hypertensive emergency	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.

Measure	Brivaracetam Focal Epilepsy (SS) n=19 participants at risk This arm includes subjects with focal epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).	Brivaracetam Generalized Epilepsy (SS) n=7 participants at risk This arm includes subjects with generalized epilepsy, who received a flexible dose of Brivaracetam (BRV) tablets, administered twice a day, starting with an individual dose that they had reached at the completion of study N01395 (feeder study). The BRV dose could have been increased or decreased in increments of 50mg/day based on the individual subject's seizure control and/or tolerability, but was to not exceed 200mg/day. This arm is part of the Safety Set (SS).
Gastrointestinal disorders Nausea	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Gastrointestinal disorders Diarrhoea	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Gastrointestinal disorders Vomiting	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
General disorders Fatigue	15.8% 3/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
General disorders Oedema peripheral	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Urinary tract infection	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	28.6% 2/7 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Bronchitis	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Upper respiratory tract	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	28.6% 2/7 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Nasopharyngitis	10.5% 2/19 • Number of events 4 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Pharyngitis streptococcal	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Infections and infestations Sinusitis	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Investigations Crystal urine present	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Investigations Gamma-glutamyltransferase increased	5.3% 1/19 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Investigations Neutrophil count increased	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Investigations Protein urine present	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Investigations Urinary casts	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Investigations White blood cell count increased	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Musculoskeletal and connective tissue disorders Back pain	15.8% 3/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Nervous system disorders Headache	36.8% 7/19 • Number of events 68 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Nervous system disorders Convulsion	15.8% 3/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Nervous system disorders Dizziness	15.8% 3/19 • Number of events 29 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Psychiatric disorders Anxiety	10.5% 2/19 • Number of events 3 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Psychiatric disorders Depression	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Reproductive system and breast disorders Dysmenorrhoea	5.3% 1/19 • Number of events 20 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	14.3% 1/7 • Number of events 1 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.5% 2/19 • Number of events 2 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.	0.00% 0/7 • Adverse events collection started at Day 0 and continued up to 30 days after last intake of study medication.