Trial Outcomes & Findings for Comparison of Increasing Doses of Tapentadol Versus a Combination of Tapentadol and Pregabalin (NCT NCT01352741)

NCT ID: NCT01352741

Last Updated: 2019-10-28

Results Overview

The primary endpoint is defined as the comparison of tapentadol prolonged release (PR) 300 mg plus 200 mg per day and the combination of tapentadol PR 300 mg per day and pregabalin 300 mg per day regarding the change in NRS-3 pain intensity scores (recalled average pain intensity score during the last 3 days on 11-point NRS, where 0 is the no pain and 10 is pain as bad as you can imagine) from the randomization visit to the final evaluation visit. Theoretically a maximum decrease of -10 and an increase of +4 in the pain intensity would have been possible. A negative sign indicates a decrease in pain intensity from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline visit).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 622 participants
• Primary outcome timeframe: Randomization (Day 22); Final Evaluation Visit (Day 77)
• Results posted on: 2019-10-28

Participant Flow

The trial started on 23 Mar 2011 and the last participant completed the last follow-up examination on the 17 Jan 2012.

622 participants signed an informed consent. All participants included in the 8 week Double Blind Comparative Period were initially in the open-label titration period. Participants in the open-label tapentadol continuation period were in the open-label titration period but did not enter the comparative period.

Participant milestones

Measure	Tapentadol Prolonged Release All participants entered the 3-week Titration Period, Tapentadol Prolonged Release was administered in an open-label fashion. Participants that did not qualify for entry into the Comparative Period were able to enter the open-label Continuation Period. During the double-blind comparator phase the dose was increased to 200 mg twice daily and after a week to 250 mg twice daily. Participants that dropped out due to tolerability issues during the comparative period were able to enter the open-label pick-up arm.	Tapentadol Prolonged Release and Pregabalin At the end of the Open-label Tapentadol Titration Period participants that qualified were randomized to either tapentadol or tapentadol and pregabalin treatment. In this double-blind period participants started on Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day.
Open-label Tapentadol Titration Period STARTED	445	0
Open-label Tapentadol Titration Period Switched to Open-label Continuation Arm	59	0
Open-label Tapentadol Titration Period Full Analysis Set	436	0
Open-label Tapentadol Titration Period COMPLETED	372	0
Open-label Tapentadol Titration Period NOT COMPLETED	73	0
Double-blind Comparative Period STARTED	154	159
Double-blind Comparative Period Switched to Open-label Pick-up Arm	19	18
Double-blind Comparative Period No Pain Assessments Available	2	2
Double-blind Comparative Period Full Analysis Set	152	157
Double-blind Comparative Period Major Protocol Deviations	13	8
Double-blind Comparative Period Per Protocol Set	139	149
Double-blind Comparative Period painDetect Per Protocol Set	109	127
Double-blind Comparative Period SF-12 Per Protocol Set	131	143
Double-blind Comparative Period EQ-5D Per Protocol Set	131	143
Double-blind Comparative Period HADS Per Protocol Set (PPS)	123	137
Double-blind Comparative Period Sleep Evaluation (Latency) PPS	123	137
Double-blind Comparative Period Sleep Evaluations (Awakenings) PPS	123	137
Double-blind Comparative Period Sleep Evaluations (Hours Slept) PPS	123	137
Double-blind Comparative Period COMPLETED	126	133
Double-blind Comparative Period NOT COMPLETED	28	26
Open-Label Tapentadol Continuation Arm STARTED	59	0
Open-Label Tapentadol Continuation Arm Major Protocol Deviation	2	0
Open-Label Tapentadol Continuation Arm Full Analysis Set	57	0
Open-Label Tapentadol Continuation Arm COMPLETED	51	0
Open-Label Tapentadol Continuation Arm NOT COMPLETED	8	0
Open-Label Tapentadol Pick-Up Arm STARTED	37	0
Open-Label Tapentadol Pick-Up Arm COMPLETED	37	0
Open-Label Tapentadol Pick-Up Arm NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Tapentadol Prolonged Release All participants entered the 3-week Titration Period, Tapentadol Prolonged Release was administered in an open-label fashion. Participants that did not qualify for entry into the Comparative Period were able to enter the open-label Continuation Period. During the double-blind comparator phase the dose was increased to 200 mg twice daily and after a week to 250 mg twice daily. Participants that dropped out due to tolerability issues during the comparative period were able to enter the open-label pick-up arm.	Tapentadol Prolonged Release and Pregabalin At the end of the Open-label Tapentadol Titration Period participants that qualified were randomized to either tapentadol or tapentadol and pregabalin treatment. In this double-blind period participants started on Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day.
Open-label Tapentadol Titration Period Protocol Violation	4	0
Open-label Tapentadol Titration Period Lack of Efficacy	19	0
Open-label Tapentadol Titration Period Adverse Event	34	0
Open-label Tapentadol Titration Period Withdrawal of consent	7	0
Open-label Tapentadol Titration Period Non-compliance with Trial Requirements	5	0
Open-label Tapentadol Titration Period Other	4	0
Double-blind Comparative Period Protocol Violation	2	0
Double-blind Comparative Period Lack of Efficacy	0	3
Double-blind Comparative Period Adverse Event	16	17
Double-blind Comparative Period Lost to Follow-up	1	0
Double-blind Comparative Period Death	0	1
Double-blind Comparative Period Withdrawal of consent	8	3
Double-blind Comparative Period Other	1	2
Open-Label Tapentadol Continuation Arm Adverse Event	4	0
Open-Label Tapentadol Continuation Arm Lack of Efficacy	1	0
Open-Label Tapentadol Continuation Arm Withdrawal by Subject	2	0
Open-Label Tapentadol Continuation Arm Protocol Violation	1	0

Baseline Characteristics

Comparison of Increasing Doses of Tapentadol Versus a Combination of Tapentadol and Pregabalin

Baseline characteristics by cohort

Measure	All Trial Participants n=445 Participants All participants that received at least one dose of tapentadol prolonged release at baseline, in the open-label titration period.
Age, Continuous	57.9 years STANDARD_DEVIATION 11.30 • n=5 Participants
Sex: Female, Male Female	262 Participants n=5 Participants
Sex: Female, Male Male	183 Participants n=5 Participants
Race/Ethnicity, Customized White	441 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants
Region of Enrollment Spain	54 participants n=5 Participants
Region of Enrollment Belgium	45 participants n=5 Participants
Region of Enrollment Poland	102 participants n=5 Participants
Region of Enrollment Denmark	41 participants n=5 Participants
Region of Enrollment Austria	55 participants n=5 Participants
Region of Enrollment Netherlands	26 participants n=5 Participants
Region of Enrollment Germany	122 participants n=5 Participants
Height	168.2 cm STANDARD_DEVIATION 9.97 • n=5 Participants
Weight	83.61 kg STANDARD_DEVIATION 17.542 • n=5 Participants
Body Mass Index (BMI)	29.57 kg/m² STANDARD_DEVIATION 5.616 • n=5 Participants
Diagnosis of Lumbar Radiculopathy Yes	310 participants n=5 Participants
Diagnosis of Lumbar Radiculopathy No	134 participants n=5 Participants
Diagnosis of Lumbar Radiculopathy Missing	1 participants n=5 Participants
History of low back pain	6.3 years n=5 Participants
Subject's satisfaction with previous treatment Poor	126 participants n=5 Participants
Subject's satisfaction with previous treatment Fair	233 participants n=5 Participants
Subject's satisfaction with previous treatment Good	68 participants n=5 Participants
Subject's satisfaction with previous treatment Very Good	10 participants n=5 Participants
Subject's satisfaction with previous treatment Excellent	1 participants n=5 Participants
Subject's satisfaction with previous treatment Missing	7 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization (Day 22); Final Evaluation Visit (Day 77)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The primary endpoint is defined as the comparison of tapentadol prolonged release (PR) 300 mg plus 200 mg per day and the combination of tapentadol PR 300 mg per day and pregabalin 300 mg per day regarding the change in NRS-3 pain intensity scores (recalled average pain intensity score during the last 3 days on 11-point NRS, where 0 is the no pain and 10 is pain as bad as you can imagine) from the randomization visit to the final evaluation visit.

Theoretically a maximum decrease of -10 and an increase of +4 in the pain intensity would have been possible. A negative sign indicates a decrease in pain intensity from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (Baseline visit).

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Change in the Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)	-1.6 units on a scale Standard Deviation 2.52	-1.7 units on a scale Standard Deviation 2.48	—

SECONDARY outcome

Timeframe: Enrollment (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed values.

The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine. This is the treatment period prior to the primary outcome period.

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Enrollment Visit (N=438)	7.2 units on a scale Standard Deviation 1.21	—	—
Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Baseline Visit (N=440)	8.3 units on a scale Standard Deviation 1.14	—	—
Open-label Titration Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Randomization Visit (N=377)	5.4 units on a scale Standard Deviation 1.83	—	—

SECONDARY outcome

Timeframe: Enrollment (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Observed values.

The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine.

Outcome measures

Measure	Tapentadol Prolonged Release n=59 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Enrollment Visit (N=56)	7.3 units on a scale Standard Deviation 1.30	—	—
Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Baseline Visit (N=57)	7.9 units on a scale Standard Deviation 1.23	—	—
Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Randomization Visit (N=57)	2.6 units on a scale Standard Deviation 1.27	—	—
Open-label Continuation Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3) Final Evaluation Visit (N=59)	2.6 units on a scale Standard Deviation 2.09	—	—

SECONDARY outcome

Timeframe: Final Evaluation Visit (Day 77)

Population: Observed.

The recalled average pain intensity score on the NRS-3 was assessed using an 11-point Numeric Rating Scale (NRS). This scale recalls the average pain intensity during the last 3 days. The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your pain on average during the last 3 days (the last 72 hours prior to the visit)". Where 0 = no pain and 10 indicates pain as bad as you can imagine.

Outcome measures

Measure	Tapentadol Prolonged Release n=19 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=18 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
End of Open-label Pick-up Period: Average Pain Intensity Score for the Overall Low Back Pain on an 11-point Numeric Rating Scale (NRS-3)	4.4 units on a scale Standard Deviation 2.83	4.5 units on a scale Standard Deviation 1.96	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The NRS-3 pain intensity score at the visits in the open-label titration period for the two comparative double-blind period treatment groups analyzed is reported. NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on an 11-point NRS) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot) is reported. Where 0 = no pain and 10 indicates pain as bad as you can imagine.

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Radiating Pain Baseline Visit (N=440)	8.0 units on a scale Standard Deviation 1.60	—	—
Open-label Titration Period: Radiating Pain Randomization Visit (N=377)	5.3 units on a scale Standard Deviation 2.16	—	—
Open-label Titration Period: Radiating Pain Enrollment Visit (N=438)	7.0 units on a scale Standard Deviation 1.64	—	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The NRS-3 pain intensity score at the visits in the open-label titration period for the two comparative double-blind period treatment groups analyzed is reported. NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on an 11-point NRS) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot) is reported. Where 0 = no pain and 10 indicates pain as bad as you can imagine.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Radiating Mean Pain Intensity Score for the Comparative Period Population Enrollment Visit (N=138; N=149)	7.1 units on a scale Standard Deviation 1.75	6.9 units on a scale Standard Deviation 1.49	—
Open-label Titration Period: Radiating Mean Pain Intensity Score for the Comparative Period Population Baseline Visit (N=139; N=149)	8.1 units on a scale Standard Deviation 1.84	8.1 units on a scale Standard Deviation 1.37	—
Open-label Titration Period: Radiating Mean Pain Intensity Score for the Comparative Period Population Randomization Visit (N=139; N=149)	5.6 units on a scale Standard Deviation 1.87	5.7 units on a scale Standard Deviation 1.86	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22); End of Evaluation Visit (Day 77)

Population: Double-blind comparative population. Per Protocol Set (PPS).

NRS-3 pain intensity score (recalled average pain intensity score during the last 3 days on 11-point NRS, where 0 is the no pain and 10 is pain as bad as you can imagine) for radiating pain (pain radiating into or towards the leg, typically of shooting, radiating character, usually radiating below the knee towards the foot).

The value reported represents the change from the randomization visit (i.e., the last 3 days in the titration period) to the end of the double-blind comparative period (i.e., the last 3 days in the comparative period). The theoretical values range from -10 to 10. A negative sign indicates a decrease in pain from the start of treatment. The higher the absolute values, the greater the change since the start of treatment (baseline visit).

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in NRS-3 Pain Intensity Score for the Radiating Pain	-1.5 units on a scale Standard Deviation 2.61	-1.9 units on a scale Standard Deviation 2.60	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day -14); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.

The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit".

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours Enrollment Visit (N=438)	7.6 units on a scale Standard Deviation 1.32	—	—
Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours Baseline Visit (N=440)	8.5 units on a scale Standard Deviation 1.11	—	—
Open-label Titration Period: Worst Mean Pain Intensity Scores Over the Past 24 Hours Randomization Visit (N=377)	5.8 units on a scale Standard Deviation 1.98	—	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (day 1); Randomization Visit (Day 22)

Population: Double-blind comparative population. Per Protocol Set (PPS)

The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric Rating Scale (NRS), where 0 = "no pain" and 10 = "pain as bad as you can imagine".

The participant was asked : "Please rate your pain intensity by assessing the one number that best describes your worst pain during the past 24 hours prior to the visit".

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours Enrollment Visit (N=138; N=149)	7.8 units on a scale Standard Deviation 1.21	7.5 units on a scale Standard Deviation 1.27	—
Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours Baseline Visit (N=139; N=149)	8.5 units on a scale Standard Deviation 1.07	8.7 units on a scale Standard Deviation 0.97	—
Open-label Titration Period: Comparative Double-blind Period Population Worst Mean Pain Intensity Scores Over the Past 24 Hours Randomization Visit (N=139; N=149)	6.3 units on a scale Standard Deviation 1.52	6.4 units on a scale Standard Deviation 1.4	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-blind comparative population. Per Protocol Set (PPS).

The recalled worst pain intensity during the last 24 hours was assessed using an 11-point Numeric rating scale, where 0 = no pain and 10 = pain as bad as you can imagine.

The participant was asked: "Please rate your pain intensity by assessing the one number that best describes your worst pain during the last 24 hours prior to the visit".

A negative change indicates that the pain intensity decreased from the start of the trial.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in Worst Pain Intensity Over the Past 24 Hours	-1.7 units on a scale Standard Deviation 2.67	-1.8 units on a scale Standard Deviation 2.58	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear".

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: painDETECT Assessments Enrollment Visit (N=438)	21.4 units on a scale Standard Deviation 5.46	—	—
Open-label Titration Period: painDETECT Assessments Baseline Visit (N=440)	22.7 units on a scale Standard Deviation 5.74	—	—
Open-label Titration Period: painDETECT Assessments Randomization Visit (N=377)	16.9 units on a scale Standard Deviation 6.57	—	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-blind comparative population. Per Protocol Set (PPS).

The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear".

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment Enrollment Visit (N=138; N=149)	21.6 units on a scale Standard Deviation 5.23	21.7 units on a scale Standard Deviation 5.17	—
Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment Baseline Visit (N=139; N=149)	22.4 units on a scale Standard Deviation 5.21	23.8 units on a scale Standard Deviation 5.51	—
Open-label Titration Period: Comparative Double-blind Period Population painDETECT Assessment Randomization Visit (N=138; N=149)	17.6 units on a scale Standard Deviation 5.93	18.4 units on a scale Standard Deviation 5.90	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-blind comparative population. Per Protocol Set (PPS).

The painDETECT was a participant completed questionnaire. The questionnaire consists of 14 questions in four domains. Based on these questions a final assessment score was calculated. The minimum score ranged from zero to a maximum of 38. Participants with a score between 0 and 12 were scored as being "negative" (had no neuropathic pain component). A value between 19 and 38 was rated as being "positive" (neuropathic component present). Values from 13 to 18 were scored as being "unclear". The theoretical range of change in this trial ranged from -38 to 19. A negative change indicated a decrease in their neuropathic component of pain.

Outcome measures

Measure	Tapentadol Prolonged Release n=109 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=127 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in painDETECT Final Assessment Change from Baseline	-10.2 units on a scale Standard Deviation 8.57	-11.0 units on a scale Standard Deviation 7.73	—
Double-blind Comparative Period: Change in painDETECT Final Assessment Change from Randomization	-6.0 units on a scale Standard Deviation 8.99	-5.9 units on a scale Standard Deviation 7.22	—

SECONDARY outcome

Timeframe: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 100.

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment Overall Score Enrollment Visit (N=438)	55.2 units on a scale Standard Deviation 16.86	—	—
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment Overall Score Baseline Visit (N=440)	62.7 units on a scale Standard Deviation 18.41	—	—
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment Overall Score Randomization Visit (N=377)	42.0 units on a scale Standard Deviation 20.29	—	—

SECONDARY outcome

Timeframe: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-blind comparative population. Per Protocol Set (PPS).

In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale; from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. worst burning imaginable). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) sub-scores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 100.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population Overall Score Enrollment Visit (N=138, N=149)	54.8 units on a scale Standard Deviation 15.12	57.6 units on a scale Standard Deviation 16.07	—
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population Overall Score Baseline Visit (N=139, N=149)	62.8 units on a scale Standard Deviation 17.13	65.4 units on a scale Standard Deviation 18.29	—
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population Overall Score Randomization Visit (N=139, N=149)	45.2 units on a scale Standard Deviation 17.99	46.5 units on a scale Standard Deviation 18.57	—
Open-label Titration Period: Neuropathic Pain Symptom Inventory (NPSI) Overall Score Assessment in the Double-blind Comparative Period Population Overall Score Final Evaluation Visit(N=131, N=143)	28.9 units on a scale Standard Deviation 21.78	30.5 units on a scale Standard Deviation 22.38	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-blind comparative population. Per Protocol Set (PPS).

In the Neuropathic Pain Symptom Inventory (NPSI) the participant rated their symptoms of neuropathic pain. Ten pain questions were answered on an 11-point scale, from 0 (symptom not present) to 10 (symptom at its worst imaginable intensity, e.g. Spontaneous Pressing Pain Subscore). The overall NPSI score was calculated by the summation of all ten responses and ranges between 0 and 100. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) subscores are reported. The overall values reported for all participants that completed the questionnaire are shown. A symptom was absent if the value is 0, the symptom was present in all participants and all participants rated it at its worst possible intensity if a value is 10 (100 for the overall score) . A negative change indicates that the intensity of the symptom has decreased since the start of treatment.

Outcome measures

Measure	Tapentadol Prolonged Release n=131 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=143 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment Overall Score	-16.8 units on a scale Standard Deviation 18.95	-16.6 units on a scale Standard Deviation 20.04	—
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment Subscore: Superficial Spontaneous Burning	-1.9 units on a scale Standard Deviation 2.75	-2.3 units on a scale Standard Deviation 2.65	—
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment Subscore: Deep Sponatenous Pressing Pain	-1.4 units on a scale Standard Deviation 2.26	-1.4 units on a scale Standard Deviation 2.58	—
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment Subscore: Paroxysmal Pain	-2.0 units on a scale Standard Deviation 2.39	-1.6 units on a scale Standard Deviation 2.44	—
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment Subscore: Evoked Pain	-1.8 units on a scale Standard Deviation 2.28	-1.7 units on a scale Standard Deviation 2.32	—
Double-blind Comparative Period: Change in Neuropathic Pain Symptom Inventory (NPSI) Sub-scores and Overall Score Assessment Subscore: Parasthesia/Dysesthesia	-1.4 units on a scale Standard Deviation 2.44	-1.5 units on a scale Standard Deviation 2.49	—

SECONDARY outcome

Timeframe: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical and mental summary scores were calculated from the individual responses. A higher score indicates a better perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) Randomization Visit (N=139; N=149)	34.1 units on a scale Standard Deviation 9.36	34.1 units on a scale Standard Deviation 8.45	—
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) Enrollment Visit (N=138; N=149)	29.9 units on a scale Standard Deviation 8.55	29.8 units on a scale Standard Deviation 7.56	—
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) Baseline Visit (N=139; N=149)	28.2 units on a scale Standard Deviation 8.17	28.5 units on a scale Standard Deviation 7.68	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The physical summary scores were calculated from the individual responses to those questions covering physical health. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state.

The change in the SF-12 score shows an improvement in health from baseline if the values are positive. The higher the value the greater the improvement.

Outcome measures

Measure	Tapentadol Prolonged Release n=131 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=143 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Changes in the Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) Change from Baseline Visit	12.3 units on a scale Standard Deviation 12.98	11.1 units on a scale Standard Deviation 11.36	—
Double-blind Comparative Period: Changes in the Short Form Health Survey (SF-12) Physical Health Composite Score (PCS) Change from Randomization Visit	6.2 units on a scale Standard Deviation 13.04	5.6 units on a scale Standard Deviation 10.88	—

SECONDARY outcome

Timeframe: Enrollment Visit; Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The mental health summary scores were calculated from the individual responses to two of the 12 questions. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible mental health.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) Enrollment Visit (N=138; N=149)	46.1 units on a scale Standard Deviation 11.84	44.8 units on a scale Standard Deviation 12.24	—
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) Baseline Visit (N=139; N=149)	45.4 units on a scale Standard Deviation 12.43	43.2 units on a scale Standard Deviation 13.32	—
Open-label Titration Period: Comparative Double-blind Period Population Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) Randomization Visit (N=139; N=149)	49.2 units on a scale Standard Deviation 11.64	47.3 units on a scale Standard Deviation 11.80	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Short Form Health Survey (SF-12) has several brief broad questions on 8 aspects of health (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health) that a participant was asked to score over the last week. The mental health summary scores were calculated from the individual responses to two of the 12 questions. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible mental health.

Outcome measures

Measure	Tapentadol Prolonged Release n=131 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=143 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) Change from Baseline Visit (N=131; N=143)	3.9 units on a scale Standard Deviation 10.59	6.5 units on a scale Standard Deviation 11.62	—
Double-blind Comparative Period: Change in Short Form Health Survey (SF-12) Mental Health Composite Score (MCS) Change from Randomization Visit (N=131; N=143)	0.1 units on a scale Standard Deviation 8.42	2.5 units on a scale Standard Deviation 9.77	—

SECONDARY outcome

Timeframe: Enrollment Visit (day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population Enrollment Visit (N=138; N=149)	0.32 units on a scale Standard Deviation 0.304	0.33 units on a scale Standard Deviation 0.313	—
Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population Baseline Visit (N=139; N=149)	0.29 units on a scale Standard Deviation 0.306	0.18 units on a scale Standard Deviation 0.316	—
Open-label Titration Period: EuroQol-5 Dimension (EQ-5D) Health Status Index Score for the Double-blind Comparative Period Population Randomization Visit (N=139; N=149)	0.55 units on a scale Standard Deviation 0.254	0.52 units on a scale Standard Deviation 0.237	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The participant scored the EuroQol-5 questionnaire. The EuroQol-5 questionnaire uses a health state classification with 5 dimensions. Each dimension was assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1 (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group.

Outcome measures

Measure	Tapentadol Prolonged Release n=131 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=143 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change EuroQol-5 Dimension (EQ-5D) Health Status Index Change from Baseline Visit	0.34 units on a scale Standard Deviation 0.358	0.43 units on a scale Standard Deviation 0.386	—
Double-blind Comparative Period: Change EuroQol-5 Dimension (EQ-5D) Health Status Index Change from Randomization Visit	0.09 units on a scale Standard Deviation 0.317	0.09 units on a scale Standard Deviation 0.254	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)

Population: Double-blind comparative population. Full Analysis Set (FAS).

In the Patient Global Impression of Change (PGIC) the participant indicated the perceived change over the treatment period. PGIC is a 7 point scale where the patient's rates overall improvement. Patients rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."

Outcome measures

Measure	Tapentadol Prolonged Release n=152 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=157 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Very much improved	28 participants	32 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Much improved	44 participants	66 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Minimally improved	51 participants	31 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) No change	10 participants	10 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Minimally worse	5 participants	5 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Much worse	4 participants	5 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Very much worse	0 participants	1 participants	—
Double-blind Comparative Period: Patient Global Impression of Change (PGIC) Missing	10 participants	7 participants	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)

Population: Double-Blind Comparative Population. Full Analysis Set (FAS).

In the Clinician Global Impression of Change (CGIC) the clinician indicated the perceived change over the treatment period. The clinician was requested to choose one of seven categories for each participant. The Clinician rated the participants change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."

Outcome measures

Measure	Tapentadol Prolonged Release n=142 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=150 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Very much improved	26 participants	30 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Much improved	54 participants	82 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Minimally improved	46 participants	19 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) No change	8 participants	10 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Minimally worse	3 participants	2 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Much worse	5 participants	5 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Very much worse	0 participants	2 participants	—
Double-blind Comparative Period: Clinician Global Impression of Change (CGIC) Missing	10 participants	7 participants	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety.

A decrease in values over the trial period indicate that there has been an improvement.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population Enrollment Visit (N=138; N=149)	7.4 units on a scale Standard Deviation 4.51	8.6 units on a scale Standard Deviation 4.94	—
Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population Baseline Visit (N=139; N=149)	7.7 units on a scale Standard Deviation 4.52	9.0 units on a scale Standard Deviation 5.15	—
Open-label Titration Period: Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population Randomization Visit (N=139; N=149)	5.8 units on a scale Standard Deviation 3.77	7.1 units on a scale Standard Deviation 4.39	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe anxiety. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate anxiety. A score of 11 or above is considered to be a case of anxiety.

A negative sign indicates that there has been a decrease in anxiety since the start of treatment.

Outcome measures

Measure	Tapentadol Prolonged Release n=123 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=137 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population Change from Baseline Visit	-2.2 units on a scale Standard Deviation 3.70	-3.1 units on a scale Standard Deviation 4.28	—
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Anxiety in the Double-blind Comparative Period Population Change from Randomization Visit	-0.3 units on a scale Standard Deviation 2.93	-1.2 units on a scale Standard Deviation 3.38	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-blind Comparative Population; Per Protocol Set (PPS).

The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population Enrollment Visit (N=138; N=149)	6.9 units on a scale Standard Deviation 4.18	7.8 units on a scale Standard Deviation 4.43	—
Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population Baseline Visit (N=139; N=149)	7.6 units on a scale Standard Deviation 4.66	8.6 units on a scale Standard Deviation 4.81	—
Open-label Titration Period: Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population Randomization Visit (N=139; N=149)	6.0 units on a scale Standard Deviation 3.96	6.8 units on a scale Standard Deviation 4.24	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22); Final Evaluation Visit (Day 77)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale for the symptom severity of anxiety disorders and depression. It comprises 14 items. Seven statements describe depression. Each answer is scored on a four-point scale (0-3). All seven answers are summed to a total score with a maximum score of 21 points. A score below 7 is not considered to indicate depression. A score of 11 or above is considered to be a case of depression. A decrease in values over time indicates that there has been an improvement. A negative change value indicates a decrease in the depression score since the start of treatment.

Outcome measures

Measure	Tapentadol Prolonged Release n=123 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=137 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population Change from Baseline Visit	-2.0 units on a scale Standard Deviation 3.56	-3.1 units on a scale Standard Deviation 3.99	—
Double-blind Comparative Period: Change in Hospital Anxiety and Depression Scale - Depression in the Double-blind Comparative Period Population Change from Randomization Visit	-0.4 units on a scale Standard Deviation 3.06	-1.3 units on a scale Standard Deviation 2.94	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the sleep latency.

To assess latency the participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]?

Outcome measures

Measure	Tapentadol Prolonged Release n=438 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=440 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) n=377 Participants End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency	1.2 hours Standard Deviation 1.50	1.5 hours Standard Deviation 1.56	1.3 hours Standard Deviation 1.67

SECONDARY outcome

Timeframe: Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]? The values are for the night prior to the Randomization Visit (Baseline) and for the night prior to the Final Evaluation Visit (12 weeks after randomization). The higher the value the longer it took to fall asleep. Sleep evaluation questionnaire (SQ) items

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population Enrollment Visit (N=138, N=149)	1.3 hours Standard Deviation 1.70	1.3 hours Standard Deviation 1.52	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population Baseline Visit (N=139, N=149)	1.5 hours Standard Deviation 1.65	1.5 hours Standard Deviation 1.54	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Latency in the Double-blind Comparative Period Population Randomization Visit (N=139, N=149)	1.1 hours Standard Deviation 1.45	1.4 hours Standard Deviation 1.78	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)

Population: Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The participant was asked: How long after bedtime/lights out did you fall asleep last night [hours]? The values are for the night prior to the visits. The negative change from baseline indicates that the time to falling asleep decreased from baseline in a treatment group.

Outcome measures

Measure	Tapentadol Prolonged Release n=123 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=137 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period Sleep Evaluation Questionnaire: Change in Latency Change from baseline visit	-0.3 hours Standard Deviation 2.30	-0.3 hours Standard Deviation 2.10	—
Double-blind Comparative Period Sleep Evaluation Questionnaire: Change in Latency Change from randomization visit	0.2 hours Standard Deviation 1.88	-0.2 hours Standard Deviation 2.04	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.

How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Randomization Visit (Day 22).

The participant was asked at each visit: "How many times did you wake up during the night?"

Outcome measures

Measure	Tapentadol Prolonged Release n=438 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=440 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) n=377 Participants End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Awakenings	3.3 Number of Awakenings Standard Deviation 2.64	3.9 Number of Awakenings Standard Deviation 3.11	2.5 Number of Awakenings Standard Deviation 1.87

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.

How many times did you wake up during the night? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Randomization Visit (Day 22).

The participant was asked at each visit: "How many times did you wake up during the night?"

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population Enrollment Visit (N=138; N=149)	3.2 Number of Awakenings Standard Deviation 2.84	3.4 Number of Awakenings Standard Deviation 2.36	—
Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population Baseline Visit (N=139; N=149)	3.6 Number of Awakenings Standard Deviation 2.47	4.6 Number of Awakenings Standard Deviation 4.01	—
Open-label Titration Period: Sleep Evaluation - Number of Awakenings in the Double-blind Comparative Period Population Randomization Visit (N=139; N=149)	2.5 Number of Awakenings Standard Deviation 1.76	2.7 Number of Awakenings Standard Deviation 2.00	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1); Randomization Visit (Day 22) to Final Evaluation Visit (Day 77)

Population: Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings. Participants were asked: How many times did you wake up during the night? The change in the Number of Awakenings was calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline), for the night prior to the Baseline Visit (Day 1) and the night prior to the Final Evaluation Visit (Day 77). A negative change indicates that the number of awakenings in a treatment group have gone down since the Baseline or Randomization Visit. In general pain can interfere with sleep, one potential indicator is the number of awakenings.

Outcome measures

Measure	Tapentadol Prolonged Release n=123 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=137 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in the Number of Awakenings Change from Baseline Visit	-1.4 Number of Awakenings Standard Deviation 2.57	-2.5 Number of Awakenings Standard Deviation 3.11	—
Double-blind Comparative Period: Change in the Number of Awakenings Change from Randomization Visit	-0.2 Number of Awakenings Standard Deviation 2.01	-0.8 Number of Awakenings Standard Deviation 1.78	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the number of awakenings.

The participant was asked: "How long did you sleep last night?" [Answered in hours and minutes].

Outcome measures

Measure	Tapentadol Prolonged Release n=438 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=440 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) n=377 Participants End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Time Slept	5.8 hours Standard Deviation 1.69	5.3 hours Standard Deviation 1.79	6.4 hours Standard Deviation 1.41

SECONDARY outcome

Timeframe: Enrollment Visit (Day -12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Per Protocol Set (PPS).

The participants were requested to answer the following question:

How long did you sleep last night [hours]? The values were calculated from the data that participants self-reported for the night prior to their Randomization Visit (Baseline) and for the night prior to the End of the Continuation Visit (12 weeks after randomization).

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population Enrollment Visit (N=138, N=149)	5.8 hours Standard Deviation 1.66	5.7 hours Standard Deviation 1.70	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population Baseline Visit (N=139, N=149)	5.3 hours Standard Deviation 1.67	5.2 hours Standard Deviation 1.70	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Number of Hours Slept in the Double-blind Comparative Period Population Randomization Visit (N=139, N=149)	6.2 hours Standard Deviation 1.30	6.4 hours Standard Deviation 1.59	—

SECONDARY outcome

Timeframe: Baseline Visit (Day -12); Randomization Visit (Day 1); Final Evaluation Visit (Day 77)

Population: Per Protocol Set.

The sleep evaluation questionnaire was completed by the participant. The answer was in response to the question: Sleep evaluation: How long did you sleep last night [hours]? The value reported is the change in the number of hours of sleep from baseline. The positive value indicates that there was an increase in the number of hours of sleep in a treatment group.

Outcome measures

Measure	Tapentadol Prolonged Release n=123 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=137 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Sleep Evaluation Questionnaire - Change in the Number of Hours Slept Change from baseline visit	1.2 hours Standard Deviation 1.89	1.6 hours Standard Deviation 1.84	—
Double-blind Comparative Period: Sleep Evaluation Questionnaire - Change in the Number of Hours Slept Change from randomization visit	0.3 hours Standard Deviation 1.71	0.3 hours Standard Deviation 1.70	—

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12); Baseline Visit (Day 1); Randomization Visit (Day 22)

Population: Observed.

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=445 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) n=445 Participants End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep Excellent	9 participants	5 participants	21 participants
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep Good	110 participants	76 participants	173 participants
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep Fair	171 participants	149 participants	127 participants
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep Poor	148 participants	210 participants	56 participants
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep Missing	7 participants	5 participants	68 participants

SECONDARY outcome

Timeframe: Enrollment Visit (Day-12)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Excellent	1 participants	5 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Good	37 participants	30 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Fair	42 participants	61 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Poor	58 participants	53 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Missing	1 participants	0 participants	—

SECONDARY outcome

Timeframe: Baseline Visit (Day 1)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Excellent	2 participants	1 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Good	23 participants	17 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Fair	42 participants	49 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Poor	72 participants	82 participants	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The participant rated this categorically as being one of the following: excellent, good, fair or poor.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Excellent	7 participants	8 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Good	62 participants	59 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Fair	48 participants	56 participants	—
Open-label Titration Period: Sleep Evaluation Questionnaire - Overall Quality of Sleep in the Double-blind Comparative Period Population Poor	22 participants	26 participants	—

SECONDARY outcome

Timeframe: Randomization Visit (Day 22) to Final Evaluation (Day 77)

Population: Double-Blind Comparative Population. Per Protocol Set (PPS).

The sleep evaluation questionnaire was completed by the participant. The questionnaire measures 4 main concepts: 1 of the 4 main concepts being the overall quality of sleep.

The improvement, no change or worsening is reported based on the replies scored by the participants given at their End of Continuation Visit.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Change in the Overall Quality of Sleep Improvement	39 participants	58 participants	—
Double-blind Comparative Period: Change in the Overall Quality of Sleep No change	63 participants	59 participants	—
Double-blind Comparative Period: Change in the Overall Quality of Sleep Worsening	21 participants	20 participants	—
Double-blind Comparative Period: Change in the Overall Quality of Sleep Missing	16 participants	12 participants	—

SECONDARY outcome

Timeframe: End of Open-label Titration Period at Randomization Visit (Day 22)

Population: Last Observation Carried Forward (LOCF); Per Protocol Set

Participants rated their satisfaction with the study drug (IMPs) by answering the following question on a 5-point rating scale:

"How would you rate your overall satisfaction with your current pain treatment?": Excellent, Very Good, Good, Fair and Poor.

Outcome measures

Measure	Tapentadol Prolonged Release n=445 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Open-label Titration Period: Subject's Satisfaction With Treatment Poor	12 participants	—	—
Open-label Titration Period: Subject's Satisfaction With Treatment Fair	119 participants	—	—
Open-label Titration Period: Subject's Satisfaction With Treatment Good	178 participants	—	—
Open-label Titration Period: Subject's Satisfaction With Treatment Very Good	58 participants	—	—
Open-label Titration Period: Subject's Satisfaction With Treatment Excellent	11 participants	—	—
Open-label Titration Period: Subject's Satisfaction With Treatment Missing	67 participants	—	—

SECONDARY outcome

Timeframe: End of Comparative Period at Final Evaluation Visit (Day 77)

Population: Last Observation Carried Forward (LOCF); Per Protocol Set

Participants rated their satisfaction with the study drug (IMPs) by answering the following question on a 5-point rating scale:

"How would you rate your overall satisfaction with your current pain treatment?": Excellent, Very Good, Good, Fair and Poor.

Outcome measures

Measure	Tapentadol Prolonged Release n=139 Participants Tapentadol PR (100 - 300 mg per day) oral administration twice daily in the open-label titration period. Subsequently increased in the comparative period to Tapentadol Prolonged Release to 500 mg per day.	Tapentadol Prolonged Release and Pregabalin n=149 Participants Tapentadol Prolonged Release (100 - 300 mg per day) in the open-label titration period. Subsequently Tapentadol 300 mg per day was combined with Pregabalin at a daily dose of 300 mg per day.	Randomization Visit (Day 22) End of open-label titration period. Participants with 100 to 300 mg/day tapentadol.
Double-blind Comparative Period: Subject's Satisfaction With Treatment Poor	3 participants	6 participants	—
Double-blind Comparative Period: Subject's Satisfaction With Treatment Fair	32 participants	28 participants	—
Double-blind Comparative Period: Subject's Satisfaction With Treatment Good	43 participants	43 participants	—
Double-blind Comparative Period: Subject's Satisfaction With Treatment Very Good	32 participants	43 participants	—
Double-blind Comparative Period: Subject's Satisfaction With Treatment Excellent	21 participants	23 participants	—
Double-blind Comparative Period: Subject's Satisfaction With Treatment Missing	8 participants	6 participants	—

Adverse Events

Open-Label Tapentadol Titration Period

Serious events: 3 serious events

Other events: 227 other events

Deaths: 0 deaths

Tapentadol in the Comparative Period

Serious events: 5 serious events

Other events: 98 other events

Deaths: 0 deaths

Tapentadol and Pregabalin in the Comparative Period

Serious events: 3 serious events

Other events: 103 other events

Deaths: 0 deaths

Open-Label Tapentadol Pick-Up Arm

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Open-Label Tapentadol Continuation Period

Serious events: 2 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Open-Label Tapentadol Titration Period n=445 participants at risk During the 3-week Titration Period, Tapentadol Prolonged Release was administered in an open-label fashion. Titration dose steps on a weekly basis: First 50 mg administered twice daily, then 100 mg administered twice daily and then 150 mg administered twice daily. The titration period could be shortened to 10 days, with a participant at a predefined dose level for at least 3 days. The dose of 300 mg Tapentadol per day was maintained until the Randomization Visit.	Tapentadol in the Comparative Period n=154 participants at risk The dose of Tapentadol Prolonged Release was increased to 400 mg (2 x 200mg) and a week later to 500 mg (2 x 250 mg) per day and maintained at 500 mg per day.	Tapentadol and Pregabalin in the Comparative Period n=159 participants at risk Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day.	Open-Label Tapentadol Pick-Up Arm n=37 participants at risk Participants that drop-out of the Comparative Period, due to tolerability issues, were permitted to continue on Tapentadol Prolonged Release at either 300 mg per day or 400 mg per day.	Open-Label Tapentadol Continuation Period n=59 participants at risk Participants who did not qualify for randomization to the Comparator Period, continued on a stable dose of Tapentadol Prolonged Release 300 mg per day if they had reached a satisfactory level of pain relief.
Cardiac disorders Cardiac arrest	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Cardiac failure	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Tachycardia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Vertigo	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Endocrine disorders Goitre	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Constipation	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Nausea	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Chest pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Device dislocation	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Drug withdrawal syndrome	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Chest injury	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Fall	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Muscle contractions involuntary	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Thrombosis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.

Other adverse events

Measure	Open-Label Tapentadol Titration Period n=445 participants at risk During the 3-week Titration Period, Tapentadol Prolonged Release was administered in an open-label fashion. Titration dose steps on a weekly basis: First 50 mg administered twice daily, then 100 mg administered twice daily and then 150 mg administered twice daily. The titration period could be shortened to 10 days, with a participant at a predefined dose level for at least 3 days. The dose of 300 mg Tapentadol per day was maintained until the Randomization Visit.	Tapentadol in the Comparative Period n=154 participants at risk The dose of Tapentadol Prolonged Release was increased to 400 mg (2 x 200mg) and a week later to 500 mg (2 x 250 mg) per day and maintained at 500 mg per day.	Tapentadol and Pregabalin in the Comparative Period n=159 participants at risk Tapentadol Prolonged Release 300 mg per day (2 x 150 mg) plus Pregabalin 2 x 75 mg (total daily dose of 150 mg). A week later the dose of Pregabalin was increased to a total daily dose of 300 mg per day (2 x 150 mg), the Tapentadol Prolonged Release dose remained at 300 mg per day.	Open-Label Tapentadol Pick-Up Arm n=37 participants at risk Participants that drop-out of the Comparative Period, due to tolerability issues, were permitted to continue on Tapentadol Prolonged Release at either 300 mg per day or 400 mg per day.	Open-Label Tapentadol Continuation Period n=59 participants at risk Participants who did not qualify for randomization to the Comparator Period, continued on a stable dose of Tapentadol Prolonged Release 300 mg per day if they had reached a satisfactory level of pain relief.
Infections and infestations Laryngitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Localised Infection	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Nasopharyngitis	1.6% 7/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.1% 5/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.1% 3/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Blood and lymphatic system disorders Anaemia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Atrial Fibrillation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Brachycardia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Cardiac Failure	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Cardiovascular Disorder	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Cardiac disorders Palpitation	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Cupulolithiasis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Ear Discomfort	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Ear pain	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders External Ear Disorder	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Inner Ear Disorder	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Motion Sickness	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Tinnitus	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Ear and labyrinth disorders Vertigo	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Accommodation Disorder	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Atrial Fibrillation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Dry Eye	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Eye Irritation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Eye pruritis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Vision Blurred	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Visual Acuity Reduced	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Eye disorders Visual Impairment	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal Discomfort	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal Distension	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal Pain	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal Pain Upper	1.6% 7/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abdominal Symptom	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Abnormal Faeces	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Colitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Colonic Polyp	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Constipation	5.6% 25/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	7.1% 11/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.0% 8/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	24.3% 9/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	16.9% 10/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Diarrhoea	3.1% 14/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.9% 6/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Dry Mouth	7.9% 35/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.9% 6/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.0% 8/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	16.2% 6/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	10.2% 6/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Dyspepsia	1.3% 6/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Dysphagia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Enteritis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Faeces hard	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Flatuence	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Frequent Bowel Movements	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Gastritis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Gastrointestinal Disorder	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Glossodynia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Haematochezia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Haemorrhoids	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Hyperchlorhydria	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Inflammatory Bowel Disease	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Nausea	13.0% 58/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	10.4% 16/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.8% 14/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	32.4% 12/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	18.6% 11/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Oesophagitis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Uvulitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Gastrointestinal disorders Vomiting	4.5% 20/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.8% 9/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.1% 5/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	13.5% 5/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	6.8% 4/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Asthenia	1.3% 6/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.6% 4/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Chest Discomfort	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Chills	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Discomfort	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Drug Withdrawal Syndrome	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Fatigue	5.6% 25/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.4% 13/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	10.1% 16/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	27.0% 10/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.5% 5/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Feeling Abnormal	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Feeling Cold	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Feeling Drunk	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Feeling Hot	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Gait Disturbance	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Generalised Oedema	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Hyperplasia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Inflammation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Influenza Like Illness	0.90% 4/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Irritability	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Malaise	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Oedema Peripheral	1.3% 6/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Pyrexia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
General disorders Thirst	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Immune system disorders Seasonal Allergy	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Abdominal Abscess	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Acute Tonsillitis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Bacterial Infection	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Bronchitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Cystitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Diverticulitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Ear Infection	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Gastroenteritis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Gastroenteritis Viral	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Gastrointestinal Infection	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Herpes Zoster Oticus	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Infection	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Influenza	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Oral Herpes	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Otitis Media Acute	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Pharyngitis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Pneumonia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Rhinitis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Sinusitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Upper Respiratory Tract Infection	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Urinary Tract Infection	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Infections and infestations Vaginal Infection	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Ankle Fracture	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Contusion	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Excoriation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Fall	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.5% 4/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Laceration	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Ligament Sprain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Muscle Rupture	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Post Procedural Complication	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Injury, poisoning and procedural complications Procedural Pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Alanine Aminotransferase Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Aspartate Aminotransferase Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Blood Creatinine Decreased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Blood Pressure Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Blood Triglycerides Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Reproductive system and breast disorders Erectile Dysfunction	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Gamma-Glutamyltransferase Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Haemoglobin Decreased	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Lasegue's Test Positive	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Lipase Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Neurological Examination Abnormal	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Nitrite Urine Present	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Prostatic Specifc Antigen Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Protein Urine Present	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations Weight Decreased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Investigations White Blood Cell Count Increased	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Metabolism and nutrition disorders Decreased Appetite	2.7% 12/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Metabolism and nutrition disorders Diabetes Mellitus	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Metabolism and nutrition disorders Dyslipidaemia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Metabolism and nutrition disorders Hypercholesterolaemia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Metabolism and nutrition disorders Increased Appetite	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Arthralgia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Bursitis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Flank Pain	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Groin Pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protusion	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Joint Swelling	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Muscle Fatigue	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.90% 4/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Muscle Twitching	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Musculoskeletal Stiffness	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.6% 4/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Sensation of Heaviness	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Musculoskeletal and connective tissue disorders Tendonitis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Allodynia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Aphasia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Balance Disorder	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Carotid Arteriosclerosis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Disturbance in Attention	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Dizziness	11.5% 51/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	11.0% 17/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	17.6% 28/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	29.7% 11/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	15.3% 9/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Dysaesthesia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Dysarthria	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Dysgeusia	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Dyskinesia	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Headache	9.0% 40/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	6.5% 10/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.2% 13/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	13.5% 5/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	11.9% 7/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Hypoaesthesia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Hyporeflexia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Hypotonia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Lethargy	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Memory Impairment	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Mental Impairment	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Movement Disorder	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Muscle Contraction Involuntary	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Paraesthesia	1.1% 5/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Restless Leg Syndrome	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Sciatica	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Sedation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Sensory Loss	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Somnolence	6.5% 29/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.4% 13/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	11.9% 19/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	29.7% 11/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	6.8% 4/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Speech Disorder	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Syncope	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Tension Headache	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Nervous system disorders Tremor	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Abnormal Dreams	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Aggression	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Agitation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Anxiety	0.90% 4/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.6% 4/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Apathy	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Confusional State	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Depressed Mood	0.90% 4/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Depression	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Disorientation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Drug Dependence	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Emotional Disorder	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Fear	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Food Aversion	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Hallucination, Visual	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Initial Insomnia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Insomnia	1.8% 8/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.1% 5/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.1% 3/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Libido decreased	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Listless	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Middle Insomnia	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Mood Swings	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Mood Altered	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Nervousness	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Nightmare	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.1% 3/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Restlessness	1.1% 5/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Sleep Disorder Due To General Medical Condition, Insomnia Type	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Sleep Talking	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Sleep disorder	0.90% 4/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Suicidal Ideation	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Psychiatric disorders Tic	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Bladder Discomfort	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Dysuria	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.9% 3/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Glycosuria	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Micturition Disorder	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Nephrolithiasis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Oliguria	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Pollakiuria	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Renal Colic	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Renal and urinary disorders Renal Cyst	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Reproductive system and breast disorders Breast Swelling	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Reproductive system and breast disorders Sexual Dysfunctio	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Apnoea	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Cough	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.6% 4/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Dry Throat	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 5/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	5.4% 2/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Acne	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Dry Skin	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Erythema	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.7% 21/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	11.7% 18/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	6.3% 10/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	27.0% 10/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.5% 5/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Night Sweats	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Pain of Skin	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Pruritus	2.2% 10/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.9% 6/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	10.8% 4/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.4% 2/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Pruritus Generalised	0.90% 4/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Rash	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Rash Pruritic	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Skin Discolouration	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Skin Tightness	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Skin and subcutaneous tissue disorders Urticaria	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Surgical and medical procedures Tooth Extraction	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Blood Pressure Fluctuation	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Flushing	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Haematoma	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Hot Flush	2.2% 10/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	8.1% 3/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Hypertension	0.67% 3/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	3.1% 5/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Hypertensive crisis	0.22% 1/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Hypotension	0.45% 2/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.3% 2/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	2.7% 1/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Thrombophlebitis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.65% 1/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Thrombosis	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.63% 1/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.
Vascular disorders Venous Thrombosis Limb	0.00% 0/445 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/154 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/159 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	0.00% 0/37 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.	1.7% 1/59 • Baseline Visit; up to end of Week 11. Treatment Emergent Adverse Events are reported, starting with the first dose in the open-label titration period on Day 1 up to Day 77. TEAEs are reported up to Day 91 at the End of the Follow-Up visit. One participant died, before the baseline visit, during the washout phase of the clinical trial.

Additional Information

Director of Clinical Trials

Grünenthal GmbH

Phone: +49 241 569 3223

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
• Publication restrictions are in place

Restriction type: OTHER