Trial Outcomes & Findings for Open-label Extension to Protocol 1042-0600 (NCT NCT00512317)

NCT ID: NCT00512317

Last Updated: 2023-01-17

Results Overview

Percent Change in weekly seizure frequency by treatment group compared to Baseline at the beginning of the double-blind study 1042-0600 is presented. Weekly seizure frequency included partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS) during Weeks 1 through Week 117. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 123 participants
• Primary outcome timeframe: Baseline (Day 0) and Week 1 through Week 117
• Results posted on: 2023-01-17

Participant Flow

Participants who completed the previous double-blind controlled trial (Protocol 1042-0600, NCT00465517) were enrolled in this study.

Participant milestones

Measure	Ganaxolone Participants were administered ganaxolone (GNX) dose which ranged from 600 milligrams per day (mg/day) to 1500 mg/day oral liquid suspension. The dose titration schedule started with 300 mg three times daily (tid) (900 mg/day) and increased every 2 days by 100 mg tid (300 mg/day) to 500 mg tid (1500 mg/day). Participants who were able to tolerate the starting dose of 900 mg/day, were moved to increase dose of 1200 mg/day for 2 days, and then to 1500 mg/day until the optimal dose for efficacy and tolerability was achieved.
Overall Study STARTED	123
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	117

Reasons for withdrawal

Measure	Ganaxolone Participants were administered ganaxolone (GNX) dose which ranged from 600 milligrams per day (mg/day) to 1500 mg/day oral liquid suspension. The dose titration schedule started with 300 mg three times daily (tid) (900 mg/day) and increased every 2 days by 100 mg tid (300 mg/day) to 500 mg tid (1500 mg/day). Participants who were able to tolerate the starting dose of 900 mg/day, were moved to increase dose of 1200 mg/day for 2 days, and then to 1500 mg/day until the optimal dose for efficacy and tolerability was achieved.
Overall Study Insufficient clinical response	36
Overall Study Withdrawal by Subject	23
Overall Study Sponsor closure of study	21
Overall Study <50% reduction in seizure frequency on or after Visit 7	18
Overall Study Adverse Event	13
Overall Study Discretion of the investigator or sponsor	2
Overall Study Lost to Follow-up	2
Overall Study Other	2

Baseline Characteristics

Open-label Extension to Protocol 1042-0600

Baseline characteristics by cohort

Measure	Ganaxolone n=123 Participants Participants were administered GNX dose which ranged from 600 mg/day to 1500 mg/day oral liquid suspension. The dose titration schedule started with 300 mg three times daily (tid) (900 mg/day) and increased every 2 days by 100 mg tid (300 mg/day) to 500 mg tid (1500 mg/day). Participants who were able to tolerate the starting dose of 900 mg/day, were moved to increase dose of 1200 mg/day for 2 days, and then to 1500 mg/day until the optimal dose for efficacy and tolerability was achieved.
Age, Continuous	39.4 Years STANDARD_DEVIATION 11.38 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	114 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants
Race (NIH/OMB) White	107 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 1 through Week 117

Population: Intent-To-Treat (ITT) Population included all participants who received at least 1 dose of open-label study medication. Only participants who received at least 1 dose of ganaxolone in the open-label (OL) study (1042-0601), had seizure diary data for Baseline (from double-blind study 1042-0600), and who had data from at least 7 seizure diaries in the open-label study (1042-0601) were included. Only those participants with data available at the specified data points were analyzed.

Percent Change in weekly seizure frequency by treatment group compared to Baseline at the beginning of the double-blind study 1042-0600 is presented. Weekly seizure frequency included partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS) during Weeks 1 through Week 117. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600.

Outcome measures

Measure	GNX/GNX n=79 Participants Ganaxolone in 1042-600 followed by Ganaxolone in Extension Study	PBO/GNX n=41 Participants Placebo (PBO) In 1042-600 followed by Ganaxolone in Extension Study
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks 1-10	-14.8 Percent Change Standard Deviation 54.86	-12.3 Percent Change Standard Deviation 64.08
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks 1-13	-14.0 Percent Change Standard Deviation 52.91	-13.7 Percent Change Standard Deviation 65.60
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >13-26	-19.6 Percent Change Standard Deviation 42.38	-19.8 Percent Change Standard Deviation 56.43
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >26-39	-37.7 Percent Change Standard Deviation 33.79	-48.6 Percent Change Standard Deviation 37.54
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >39-52	-29.1 Percent Change Standard Deviation 51.26	-42.9 Percent Change Standard Deviation 59.81
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >52-65	-29.9 Percent Change Standard Deviation 51.85	-43.1 Percent Change Standard Deviation 59.45
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >65-78	-41.4 Percent Change Standard Deviation 38.21	-67.7 Percent Change Standard Deviation 23.09
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >78-91	-38.8 Percent Change Standard Deviation 66.24	-43.6 Percent Change Standard Deviation 37.60
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >91-104	-69.4 Percent Change Standard Deviation 43.96	-100 Percent Change Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 Weeks >104-117	-93.3 Percent Change Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed	—

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 1 through Week 117

Population: ITT Population. Only subjects who received at least 1 dose of ganaxolone in the open-label study (1042-0601), had seizure diary data for Baseline (from double-blind study 1042-0600), and who had data from at least 7 seizure diaries in the open-label study (1042-0601) were included. Only those participants with data available at the specified data points were analyzed.

Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600.

Outcome measures

Measure	GNX/GNX n=79 Participants Ganaxolone in 1042-600 followed by Ganaxolone in Extension Study	PBO/GNX n=41 Participants Placebo (PBO) In 1042-600 followed by Ganaxolone in Extension Study
Number of Responders During Weeks 1 Through 117 Weeks 1-10	22 Participants	11 Participants
Number of Responders During Weeks 1 Through 117 Weeks 1-13	19 Participants	12 Participants
Number of Responders During Weeks 1 Through 117 Weeks >13-26	12 Participants	8 Participants
Number of Responders During Weeks 1 Through 117 Weeks >26-39	11 Participants	12 Participants
Number of Responders During Weeks 1 Through 117 Weeks >39-52	10 Participants	10 Participants
Number of Responders During Weeks 1 Through 117 Weeks >52-65	8 Participants	8 Participants
Number of Responders During Weeks 1 Through 117 Weeks >65-78	6 Participants	11 Participants
Number of Responders During Weeks 1 Through 117 Weeks >78-91	4 Participants	4 Participants
Number of Responders During Weeks 1 Through 117 Weeks >91-104	3 Participants	1 Participants
Number of Responders During Weeks 1 Through 117 Weeks >104-117	1 Participants	—

SECONDARY outcome

Timeframe: Week 1 through Week 117

Population: ITT Population. Only participants who received at least 1 dose of ganaxolone in the open-label study (1042-0601), had seizure diary data for Baseline (from double-blind study 1042-0600), and who had data from at least 7 seizure diaries in the open-label study (1042-0601) were included. Only those participants with data available at the specified data points were analyzed

Average number of seizure-free days per week for a given period was calculated as follows: (Total number of days with no seizures of any type during that period / number of days with seizure diary in that period) multiplied by 7.

Outcome measures

Measure	GNX/GNX n=79 Participants Ganaxolone in 1042-600 followed by Ganaxolone in Extension Study	PBO/GNX n=41 Participants Placebo (PBO) In 1042-600 followed by Ganaxolone in Extension Study
Number of Seizure-free Days During Weeks 1 Through 117 Weeks 1-10	4.8 Seizure free days Standard Deviation 1.99	5.0 Seizure free days Standard Deviation 1.81
Number of Seizure-free Days During Weeks 1 Through 117 Weeks 1-13	4.8 Seizure free days Standard Deviation 1.97	5.0 Seizure free days Standard Deviation 1.85
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >13-26	5.1 Seizure free days Standard Deviation 1.54	5.3 Seizure free days Standard Deviation 1.40
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >26-39	5.2 Seizure free days Standard Deviation 1.69	5.4 Seizure free days Standard Deviation 1.75
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >39-52	5.4 Seizure free days Standard Deviation 1.66	5.4 Seizure free days Standard Deviation 1.56
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >52-65	5.1 Seizure free days Standard Deviation 2.11	5.2 Seizure free days Standard Deviation 2.10
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >65-78	5.3 Seizure free days Standard Deviation 1.93	5.7 Seizure free days Standard Deviation 1.61
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >78-91	5.4 Seizure free days Standard Deviation 2.32	4.7 Seizure free days Standard Deviation 1.88
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >91-104	5.6 Seizure free days Standard Deviation 2.56	6.8 Seizure free days Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed
Number of Seizure-free Days During Weeks 1 Through 117 Weeks >104-117	6.9 Seizure free days Standard Deviation NA Standard deviation could not be calculated as a single participant was analyzed	—

SECONDARY outcome

Timeframe: Day 1 through Day 224 (Week 32)

Population: ITT Population. Only participants who received at least 1 dose of ganaxolone in the open-label study (1042-0601), had seizure diary data for Baseline (from double-blind study 1042-0600), and who had data from at least 7 seizure diaries in the open-label study (1042-0601) were included. Only those participants with data available at the specified data points were analyzed.

Number of Seizure-free participants is presented.

Outcome measures

Measure	GNX/GNX n=79 Participants Ganaxolone in 1042-600 followed by Ganaxolone in Extension Study	PBO/GNX n=41 Participants Placebo (PBO) In 1042-600 followed by Ganaxolone in Extension Study
Number of Seizure-free Participants >=91 days (13 weeks)	4 Participants	29 Participants
Number of Seizure-free Participants >=119 days (17 weeks)	43 Participants	27 Participants
Number of Seizure-free Participants >=1 day	75 Participants	41 Participants
Number of Seizure-free Participants >= 28 days (4 weeks)	20 Participants	38 Participants
Number of Seizure-free Participants >= 56 days (8 weeks)	6 Participants	33 Participants
Number of Seizure-free Participants >=70 days (10 weeks)	4 Participants	31 Participants
Number of Seizure-free Participants >=133 days (19 weeks)	3 Participants	27 Participants
Number of Seizure-free Participants >=154 days (22 weeks)	3 Participants	25 Participants
Number of Seizure-free Participants >=182 days (26 weeks)	0 Participants	20 Participants
Number of Seizure-free Participants >=224 days (32 weeks)	0 Participants	18 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) and up to Week 104

Population: ITT Population. Only participants who received at least 1 dose of ganaxolone in the open-label study (1042-0601), had seizure diary data for Baseline (from double-blind study 1042-0600), and who had data from at least 7 seizure diaries in the open-label study (1042-0601) were included. Only those participants with data available at the specified data points were analyzed.

QOLIE-31 was a survey of health-related QOL for adults with epilepsy and evaluated how much distress the participant feels about problems and worries related to epilepsy. It included 38 items grouped into eight multi-item subscales - Energy/Fatigue, Emotional Well-Being, Daily Activities/Social Functioning, Cognitive Functioning, Medication Effect, Seizure Worry, Overall Quality of Life (QoL) and Distress. The subscale scores and the total score were calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100; higher scores indicated better function. Baseline was defined as the last non-missing observation prior to the first dose in double-blind study 1042-0600. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Measure	GNX/GNX n=42 Participants Ganaxolone in 1042-600 followed by Ganaxolone in Extension Study	PBO/GNX n=18 Participants Placebo (PBO) In 1042-600 followed by Ganaxolone in Extension Study
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Energy/Fatigue	-5.7 Scores on a Scale Standard Deviation 18.16	3.9 Scores on a Scale Standard Deviation 17.20
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Emotional Well-Being	-4.7 Scores on a Scale Standard Deviation 13.83	3.3 Scores on a Scale Standard Deviation 22.13
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Social Function	-3.6 Scores on a Scale Standard Deviation 24.67	8.4 Scores on a Scale Standard Deviation 21.44
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Cognitive	2.1 Scores on a Scale Standard Deviation 19.91	2.9 Scores on a Scale Standard Deviation 18.04
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Medication Effect	-3.9 Scores on a Scale Standard Deviation 25.28	0.9 Scores on a Scale Standard Deviation 26.85
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Seizure Worry	3.6 Scores on a Scale Standard Deviation 25.40	-3.1 Scores on a Scale Standard Deviation 35.73
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Overall QoL	-3.8 Scores on a Scale Standard Deviation 17.26	0.0 Scores on a Scale Standard Deviation 15.17
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire Distress	-5.5 Scores on a Scale Standard Deviation 18.49	0.7 Scores on a Scale Standard Deviation 21.92

Adverse Events

Ganaxolone

Serious events: 15 serious events

Other events: 103 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ganaxolone n=123 participants at risk Participants were administered ganaxolone (GNX) dose which ranged from 600 mg/day to 1500 mg/day oral liquid suspension. The dose titration schedule started with 300 mg tid (900 mg/day) and increased every 2 days by 100 mg tid (300 mg/day) to 500 mg tid (1500 mg/day). Participants who were able to tolerate the starting dose of 900 mg/day, were moved to increase dose of 1200 mg/day for 2 days, and then to 1500 mg/day until the optimal dose for efficacy and tolerability was achieved.
Infections and infestations Gastroenteritis salmonella	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Convulsion	5.7% 7/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Escherichia sepsis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Pregnancy, puerperium and perinatal conditions Stillbirth	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Pneumonia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Status epilepticus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Cholelithiasis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Pancreatitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Lower limb fracture	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Hepatic enzyme increased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Osteomyelitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Paraplegia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Ileus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Tooth abscess	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Transaminases increased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Fall	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Skin laceration	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.

Other adverse events

Measure	Ganaxolone n=123 participants at risk Participants were administered ganaxolone (GNX) dose which ranged from 600 mg/day to 1500 mg/day oral liquid suspension. The dose titration schedule started with 300 mg tid (900 mg/day) and increased every 2 days by 100 mg tid (300 mg/day) to 500 mg tid (1500 mg/day). Participants who were able to tolerate the starting dose of 900 mg/day, were moved to increase dose of 1200 mg/day for 2 days, and then to 1500 mg/day until the optimal dose for efficacy and tolerability was achieved.
Blood and lymphatic system disorders Anaemia	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Blood and lymphatic system disorders Iron deficiency anaemia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Blood and lymphatic system disorders Leukopenia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Blood and lymphatic system disorders Lymphadenopathy	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Blood and lymphatic system disorders Neutropenia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Blood and lymphatic system disorders Thrombocytopenia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Cardiac disorders Angina pectoris	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Cardiac disorders Atrial flutter	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Cardiac disorders Cardiac flutter	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Cardiac disorders Chest pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Cardiac disorders Sinus tachycardia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Ear and labyrinth disorders Ear pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Ear and labyrinth disorders Tinnitus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Diplopia	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Vision blurred	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Asthenopia	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Ulcerative keratitis	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Blepharospasm	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Conjunctival hyperaemia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Eye pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Macular degeneration	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Ocular hyperaemia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Oscillopsia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Saccadic eye movement	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Eye disorders Visual acuity reduced	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Nausea	9.8% 12/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Dyspepsia	4.9% 6/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Vomiting	4.9% 6/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Diarrhoea	4.1% 5/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Abdominal pain upper	3.3% 4/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Abdominal pain	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Constipation	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Stomach discomfort	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Toothache	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Abdominal pain lower	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Cheilitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Colonic polyp	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Dental caries	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Flatulence	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Hypoaestheisa oral	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Ileus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Lip swelling	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Oral pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Pancreatitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Gastrointestinal disorders Tongue disorders	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Fatigue	16.3% 20/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Asthenia	4.9% 6/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Pyrexia	4.1% 5/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Gait disturbance	3.3% 4/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Pain	3.3% 4/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Irritability	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Non-cardiac chest pain	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Oedema peripheral	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Pitting oedema	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Facial pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Feeling abnormal	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Feeling drunk	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Influenza like illness	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
General disorders Malaise	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Hepatobiliary disorders Cholelithiasis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Immune system disorders Seasonal allergy	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Nasopharyngitis	13.8% 17/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Upper respiratory tract infection	8.1% 10/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Sinusitis	6.5% 8/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Urinary tract infection	5.7% 7/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Bronchitis	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Ear infection	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Gastroenteritis viral	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Influenza	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Localised infection	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Lower respiratory tract infection	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Pharyngitis	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Pneumonia	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Vulvovaginal mycotic infection	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Candiduria	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Cellulitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Cystitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Eye infection	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Furuncle	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Gastroenteritis salmonella	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Herpes simplex	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Laryngitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Osteomyelitis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Skin infection	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Streptococcal sepsis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Tooth abscess	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Tooth infection	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Trichomoniasis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Vaginal infection	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Viral infection	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Infections and infestations Vulval abscess	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Fall	13.8% 17/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Contusion	12.2% 15/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Skin laceration	5.7% 7/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Excoriation	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Rib fracture	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Thermal burn	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Head injury	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Joint injury	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Joint sprain	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Limb injury	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Mouth injury	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Procedural pain	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Road traffic accident	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Arthropod bite	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Back injury	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Corneal abrasion	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Eye injury	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Foot fracture	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Hand fracture	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Lower limb fracture	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Overdose	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Post procedural swelling	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Injury, poisoning and procedural complications Tendon injury	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Weight increased	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Blood glucose increased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Body temperature increased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Electrocardiogram abnormal	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Grip strength decreased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Hepatic enzyme increased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Transaminases increased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Urine analysis abnormal	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations Weight decreased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations White blood cell count decreased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Investigations White blood cells urine positive	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Metabolism and nutrition disorders Hypercholesterolaemia	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Back pain	6.5% 8/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Arthralgia	4.1% 5/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Neck pain	3.3% 4/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Muscle spasms	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Muscle twitching	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Muscular weakness	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Myalgia	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Osteoporosis	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Pain in extremity	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Bunion	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Pain in jaw	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiomyolipoma	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Headache	21.1% 26/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Convulsion	16.3% 20/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Dizziness	13.0% 16/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Somnolence	8.1% 10/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Nystagmus	5.7% 7/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Coordination abnormal	4.9% 6/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Balance disorder	3.3% 4/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Sensory loss	3.3% 4/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Cognitive disorder	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Amnesia	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Paraesthesia	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Sedation	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Aphasia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Complex partial seizures	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Grand mal convulsion	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Hypoaesthesia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Hyposmia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Intention tremor	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Lethargy	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Loss of consciousness	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Memory impairment	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Neuralgia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Neurological symptom	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Paraplegia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Post herpetic neuralgia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Postical state	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Sinus headache	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Speech disorder	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Status epliepticus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Tongue paralysis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Tremor	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Nervous system disorders Visual field defect	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Depression	4.9% 6/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Abnormal dreams	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Insomnia	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Stress	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Anxiety	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Affective disorder	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Agitation	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Depressed mood	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Nightmare	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Panic attack	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Psychiatric disorders Thinking abnormal	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Haematuria	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Nephrolithiasis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Proteinuria	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Dysuria	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Leukocyturia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Pollakiuria	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Pyuria	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Renal cyst	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Urinary incontinence	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Renal and urinary disorders Urine flow decreased	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Menorrhagia	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Menstruation irregular	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Breast tenderness	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Dysmenorrhoea	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Breast mass	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Breast swelling	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Genital pruritus female	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Haematospermia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Menometrorrhagia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Nipple pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Perineal pain	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Reproductive system and breast disorders Vaginal haemorrhage	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Nasal congestion	10.6% 13/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	6.5% 8/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Cough	5.7% 7/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Sinus congestion	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Pharyngeal erthema	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Postnasal drip	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Hiccups	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Rales	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Rash	5.7% 7/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Ecchymosis	2.4% 3/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Dermatitis contact	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Alopecia	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Erythema	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Night sweats	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Pruritus	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Skin and subcutaneous tissue disorders Swelling face	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Surgical and medical procedures Medical device change	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Surgical and medical procedures Brain lobectomy	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Surgical and medical procedures Sinus operation	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Surgical and medical procedures Uterine dilation and curettage	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Surgical and medical procedures Vasodilation procedure	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Vascular disorders Hot flush	1.6% 2/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Vascular disorders Flushing	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
Vascular disorders Vein disorder	0.81% 1/123 • Up to Week 117 AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.

Additional Information

Marinus Clinical Trials Submission Manager

Marinus Pharmaceuticals, Inc.

Phone: 484-801-4670

Email: clinicaltrials@marinuspharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place