Trial Outcomes & Findings for Lamotrigine Phase III Study in Bipolar I Disorder (NCT NCT01602510)

NCT ID: NCT01602510

Last Updated: 2017-01-23

Results Overview

TIME is defined as being the time from entry into the randomized double-blind phase to the time of the first prescription of any additional pharmacotherapy or Electroconvulsive therapy (ECT) determined by the investigator to be necessary for treatment of a relapse and/or recurrence of a depressive, manic, hypomanic or mixed episode, whichever occurs first. TIME was measured relative to randomization date. Par. prematurely discontinued from the study prior to reaching the TIME event were censored at the time of discontinuation. Analysis was performed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 265 participants
• Primary outcome timeframe: 36 weeks (wks)
• Results posted on: 2017-01-23

Participant Flow

The study consisted of 4 phases: screen phase (<2 weeks[W]), open-label phase (OLP) (Up to 16 W, lamotrigine monotherapy (LM) or combination therapy escalated to a target dose of LM 200 milligrams [mg]/day[D]), randomized double-blind phase (RDP) (up to 36 W, lamotrigine 200 mg/day or placebo) and follow-up visit (14 days after the last dose).

420 participants entered into OLP and received at least one dose of study medication. Of these 420 participants, 264 were randomized into RDP.

Participant milestones

Measure	Open Label Lamotrigine 200 mg/Day Participants (Par.) received lamotrigine escalated to a target dose of lamotrigine 200mg/day monotherapy for 6 weeks to 16 weeks. If needed, concomitant psychotropic medications were permitted during this phase however medications were discontinued at least 1 week before entering into the double-blind phase.	Randomized Placebo Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Open Label Phase STARTED	420	0	0
Open Label Phase COMPLETED	117	0	0
Open Label Phase NOT COMPLETED	303	0	0
Randomized Phase STARTED	0	133	131
Randomized Phase COMPLETED	0	59	58
Randomized Phase NOT COMPLETED	0	74	73

Reasons for withdrawal

Measure	Open Label Lamotrigine 200 mg/Day Participants (Par.) received lamotrigine escalated to a target dose of lamotrigine 200mg/day monotherapy for 6 weeks to 16 weeks. If needed, concomitant psychotropic medications were permitted during this phase however medications were discontinued at least 1 week before entering into the double-blind phase.	Randomized Placebo Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Open Label Phase Adverse Event	46	0	0
Open Label Phase Lack of Efficacy	22	0	0
Open Label Phase Protocol Violation	15	0	0
Open Label Phase Met protocol-defined stopping criteria	122	0	0
Open Label Phase Lost to Follow-up	22	0	0
Open Label Phase Physician Decision	19	0	0
Open Label Phase Withdrawal by Subject	57	0	0
Randomized Phase Adverse Event	0	2	6
Randomized Phase Lack of Efficacy	0	4	4
Randomized Phase Protocol Violation	0	3	3
Randomized Phase Met protocol-defined stopping criteria	0	58	48
Randomized Phase Lost to Follow-up	0	1	3
Randomized Phase Physician Decision	0	0	2
Randomized Phase Withdrawal by Subject	0	6	7

Baseline Characteristics

Lamotrigine Phase III Study in Bipolar I Disorder

Baseline characteristics by cohort

Measure	Open Label Lamotrigine 200 mg/Day n=420 Participants Participants (Par.) received lamotrigine escalated to a target dose of lamotrigine 200 mg/day monotherapy for 6 weeks to 16 weeks. If needed, concomitant psychotropic medications were permitted during this phase however medications were discontinued at least 1 week before entering into the double-blind phase.
Age, Continuous	35.7 Years STANDARD_DEVIATION 11.72 • n=5 Participants
Gender Female	220 Participants n=5 Participants
Gender Male	200 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	420 Participants n=5 Participants

PRIMARY outcome

Timeframe: 36 weeks (wks)

Population: Randomized (RD) Full analysis population: comprised of all randomized par. who took at least one dose of study medication and had at least one post-baseline efficacy/health outcomes assessment during randomized double-blind phase. "NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.

TIME is defined as being the time from entry into the randomized double-blind phase to the time of the first prescription of any additional pharmacotherapy or Electroconvulsive therapy (ECT) determined by the investigator to be necessary for treatment of a relapse and/or recurrence of a depressive, manic, hypomanic or mixed episode, whichever occurs first. TIME was measured relative to randomization date. Par. prematurely discontinued from the study prior to reaching the TIME event were censored at the time of discontinuation. Analysis was performed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level.

Outcome measures

Measure	Randomized Placebo n=62 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=50 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Time to Intervention for Any Mood Episode (TIME)	NA Days With less than 50% of the Participants got TIME events the median and corresponding 95% confidence interval can not be calculated	NA Days With less than 50% of the Participants got TIME events the median and corresponding 95% confidence interval can not be calculated

SECONDARY outcome

Timeframe: 36 weeks

Population: RD Full Analysis Population."NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.

TIMan was analyzed using using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level. Par. prematurely discontinued from the study prior to reaching the event were censored at the time of discontinuation.

Outcome measures

Measure	Randomized Placebo n=27 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=24 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Time to Intervention for Manic, Hypomanic or Mixed Episode (TIMan)	NA Days With less than 50% of the Participants got TIMan events the median and corresponding 95% confidence interval can not be calculated	NA Days With less than 50% of the Participants got TIMan events the median and corresponding 95% confidence interval can not be calculated

SECONDARY outcome

Timeframe: 36 weeks

Population: RD Full Analysis Population. "NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.

TIDep was analyzed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level. Par. prematurely discontinued from the study prior to reaching the event were censored at the time of discontinuation.

Outcome measures

Measure	Randomized Placebo n=35 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=26 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Time to Intervention for Depressive Episode (TIDep)	NA Days With less than 50% of the Participants got TIDep events the median and corresponding 95% confidence interval can not be calculated	NA Days With less than 50% of the Participants got TIDep events the median and corresponding 95% confidence interval can not be calculated

SECONDARY outcome

Timeframe: 36 weeks

Population: RD Full Analysis Population. "NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.

TIME-SIS was defined as the time to intervention (addition of pharmacotherapy or ECT) for any mood episode, or to the time when the participant is withdrawn for any reason after randomization. The premature discontinuation of a participant prior to reaching TIME, for any reason, was treated as an event related to bipolar disorder. All participants prematurely discontinued prior to the TIME event in this analysis were to be assumed to have reached TIME. TIMS-SIS was analyzed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level. Par. prematurely discontinued from the study prior to reaching the event were censored at the time of discontinuation.

Outcome measures

Measure	Randomized Placebo n=75 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=72 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Survival in Study (TIME-SIS).	183 Days Interval 140.0 to With less than 50% of the Participants got TIME events the upper bound of 95% confidence interval for median can not be calculated.	188 Days Interval 117.0 to With less than 50% of the Participants got TIME events the upper bound of 95% confidence interval for median can not be calculated.

SECONDARY outcome

Timeframe: Baseline and up to 36 weeks

Population: RD Full Analysis Population.

The CGI-I is a 7-point scale where investigator were asked to assess the participant's illness at the time of assessment (improved or worsened) relative to a baseline state. In this scale, 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; or 7= very much worse. Analysis was performed using Analysis of covariance with covariates of site, CGI-S baseline score and treatment. In presented Last-observation-carried-forward datasets, the last non-missing on therapy (OT) score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. Baseline value was defined as the last non-missing values at or prior to the randomization. Change from baseline at the time point of interest was calculated by subtracting the baseline values from the individual post-baseline values. If either baseline or post-baseline value was missing, the change from baseline was set to missing.

Outcome measures

Measure	Randomized Placebo n=133 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=130 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Change From Baseline in Clinical Global Impression of Improvements (CGI-I)	2.6 Score on a scale Standard Error 0.20	2.7 Score on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline and up to 36 weeks

Population: RD Full Analysis Population.

The CGI-S is a 7-point scale where investigator were asked to rate the severity of the participant's illness at the time of assessment on severity of mental illness, where 1= normal, and 7= extremely ill. Data was collected on Weeks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32 and 36. Analysis performed using Analysis of Covariance (ANCOVA) with covariates of site, CGI-S baseline score (Open label phase), treatment and CGI-S baseline score. In presented Last observation carried forward (LOCF) datasets, last non-missing on therapy score prior to TIME was carried forward to estimate missing data points for remaining study visits of treatment period. The baseline value was defined as last non-missing values at or prior to the randomization. The change from baseline at the time point of interest was calculated by subtracting the baseline values from individual post-baseline values. If either the baseline or post-baseline value was missing, the change from baseline was set to missing as well.

Outcome measures

Measure	Randomized Placebo n=133 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=130 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Change From Baseline in Clinical Global Impression of Severity (CGI-S)	0.7 Score on a scale Standard Error 0.15	0.5 Score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline and up to 36 weeks

Population: RD Full Analysis Population

HAMD consists of 17 items: depressed mood, feelings of guilt, suicide, insomnia-early, middle, late, work and activities, retardation, agitation, anxiety psychic, anxiety somatic, somatic symptoms gastro-intestinal, general somatic symptoms, hypochondriasis, loss of weight, and insight. Investigators rated par. from 0 to 4 (or 2) for these items. Total score is sum of all subscales (0 to 52, higher is worse). Data was collected on Wks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 36. Analysis was performed using ANCOVA with covariates of site, CGI-S baseline (BL) score, treatment and HAMD total BL score. The last non-missing OT score prior to TIME was carried forward to estimate missing data points for remaining study visits of the treatment period. BL value was defined as the last non-missing value at or prior to the randomization. Change from BL was calculated by subtracting BL from the specific post-BL value. If BL or post-BL value was missing, the change from BL was set to missing.

Outcome measures

Measure	Randomized Placebo n=133 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=130 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Change From Baseline in Hamilton Depression Rating Scale (HAMD)	3.0 Score on a scale Standard Error 0.83	1.8 Score on a scale Standard Error 0.84

SECONDARY outcome

Timeframe: Baseline and up to 36 weeks

Population: RD Full Analysis Population

YMRS consists of 11 items: Elevated Mood, Increased Motor Activity/Energy, Sexual Interest, Sleep, Irritability, Speech, Language/Thought Disorder, Content, Disruptive/Aggressive Behaviour, Appearance, and Insight. Investigators rated par. from 0 to 4 (or 8) for each of these items. Total score is the sum of all subscales, from 0 to 60 (higher is worse). Data was collected on Wks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 36. Analysis was performed using ANCOVA with covariates of site, CGI-S BL score, treatment and YMRS total BL score. In LOCF datasets, the last non-missing OT score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. BL value was defined as the last non-missing values at or prior to the randomization. Change from BL at the time point of interest was calculated by subtracting BL value from the individual post-BL value. If either the BL or post-BL value was missing, change from BL was set to missing.

Outcome measures

Measure	Randomized Placebo n=133 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=130 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score	2.4 Score on a scale Standard Error 0.87	2.8 Score on a scale Standard Error 0.88

SECONDARY outcome

Timeframe: Baseline and up to 36 weeks

Population: RD Full Analysis Population

For GAS, investigators rated par. for lowest level of functioning during the previous week. The scale has a 10 score categories: 1-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100, using intermediary levels when appropriate (from 100 to 1, Lower is worse.). Data was collected on Weeks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 36. Analysis was performed using ANCOVA with covariates of site, CGI-S BL score, treatment and GAS total BL score. In presented LOCF datasets, the last non-missing on therapy score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. The BL value was defined as the last non-missing values at or prior to the randomization. The change from BL at the time point of interest was calculated by subtracting the BL values from the individual post-BL values. If either the BL or post-BL value was missing, the change from BL was set to missing as well.

Outcome measures

Measure	Randomized Placebo n=133 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=130 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Change From Baseline of Global Assessment Scale (GAS) Total Score	-4.7 Score on a scale Standard Error 1.75	-4.9 Score on a scale Standard Error 1.77

SECONDARY outcome

Timeframe: Baseline and up to 36 weeks.

Population: RD Full Analysis Population. Only those par. with available data at indicated time points were analyzed.

Participant's body weight was measured on Weeks 0, 4, 8, 12, 16, 20, 24, 32 and 36. Analysis was performed using ANCOVA with covariates of site, CGI-S baseline score, treatment and baseline body weight. In presented LOCF datasets, the last non-missing on therapy score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. The baseline value was defined as the last non-missing values at or prior to the randomization. The change from baseline at the time point of interest was calculated by subtracting the baseline values from the individual post-baseline values. If either the baseline or post-baseline value was missing, the change from baseline was set to missing as well.

Outcome measures

Measure	Randomized Placebo n=133 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=128 Participants Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Change From Baseline in Body Weight	-0.72 Kilograms Standard Error 0.399	-1.56 Kilograms Standard Error 0.407

Adverse Events

Randomized Placebo

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Randomized Lamotrigine 200 mg/Day

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Measure	Randomized Placebo n=133 participants at risk Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=131 participants at risk Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Psychiatric disorders Mania	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Suicide attempt	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Concussion	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Laceration	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Brain stem infarction	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.

Other adverse events

Measure	Randomized Placebo n=133 participants at risk Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.	Randomized Lamotrigine 200 mg/Day n=131 participants at risk Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score \<= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Gastrointestinal disorders Retching	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Headache	3.0% 4/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	3.1% 4/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Poor quality sleep	3.0% 4/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Dizziness	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Somnolence	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Hypoaesthesia	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Depressed mood	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Affect lability	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Agitation	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood phosphorus increased	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood urine present	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Electrocardiogram ST segment abnormal	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Electrocardiogram T wave abnormal	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Electrocardiogram abnormal	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Heart rate decreased	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Heart rate increased	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Neutrophil count increased	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Specific gravity urine increased	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Urine ketone body present	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations White blood cell count increased	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	2.3% 3/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Chronic gastritis	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis ulcerative	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Lip ulceration	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Emotional distress	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Hyposomnia	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Initial insomnia	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Irritability	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Listless	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Sleep disorder	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Suicidal ideation	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
General disorders Fatigue	2.3% 3/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
General disorders Asthenia	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
General disorders Chest discomfort	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
General disorders Malaise	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
General disorders Thirst	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin mass	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Bundle branch block right	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Myocardial ischaemia	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Palpitations	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Sinus tachycardia	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Gout	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Granulocytopenia	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Eye disorders Dry eye	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Eye disorders Vision blurred	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Pollakiuria	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Endocrine disorders Thyroid disorder	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Immune system disorders Food allergy	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Reproductive system and breast disorders Menstrual disorder	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	3.0% 4/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	3.1% 4/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	3.0% 4/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	2.3% 3/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	3.0% 4/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Herpes zoster	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Pericoronitis	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Weight decreased	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	2.3% 3/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood creatine phosphokinase increased	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	1.5% 2/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood glucose increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood pressure increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood triglycerides increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood uric acid increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.75% 1/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Weight increased	1.5% 2/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
Investigations Bilirubin conjugated increased	0.00% 0/133 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.	0.76% 1/131 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230). On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER