Trial Outcomes & Findings for Open-label inteRventional Clinical Trial to Assess Efficacy and Safety of the exteMporaneous combInation of Nebivolol and Ramipril in hypertenSIve pAtients (NCT NCT06104423)

Last Updated: 2025-04-24

Results Overview

To assess the antihypertensive efficacy of the extemporaneous combination of Nebivolol 5 mg in combination with Ramipril 2.5 mg or 5 mg or 10 mg in lowering the sitting systolic BP between Visit 2(Week 0) and Visit 5 (Week 12) in patients with uncontrolled BP previously treated with Nebivolol 5 mg or Ramipril 5 mg monotherapies for at least 4 weeks during run-in period.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

266 participants

Primary outcome timeframe

12 weeks of combination therapy treatment. From study Visit 2 (Week 0) to study Visit 5 (Week 12)

Results posted on

2025-04-24

Participant Flow

After Screening visit, eligible patients entered a 4 week run-in period (Monotherapy period from V1 week -4 to V2 week 0) on the same day of the screening visit. Patients receiving NEB 5 mg or RAM 5 mg will continue to receive the same, while patients on any other BBs or ACE-is, will receive NEB 5 mg or RAM 5 mg respectively prior to enrolment into the study. Assessment period (Combination therapy) starts from V2 week 0 (baseline) till V5 week 12 for a total of 12 weeks

Participant milestones

Participant milestones
Measure	Nebivolol 5 mg MONOTHERAPY PERIOD 1 (4 weeks): Eligible patients entered a 4 weeks run-in period (week -4 to week 0) on the same day of the screening visit. Patients previously receiving Neb 5 mg continued the same treatment, while patients receiving any other BBs were switched to Neb 5 mg. Nebivolol 5 mg: 1 tablet of study medication (5mg) to be administered orally according to instructions of Investigator.	Ramipril 5 mg MONOTHERAPY PERIOD 1 (4 weeks): Eligible patients entered a 4 week run-in (week -4 to week 0) period on the same day of the screening visit. Patients previously receiving RAM 5 mg continued the same treatment, while patients receiving any other ACE-i were switched to RAM 5 mg. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Neb 5mg/ Ram 2.5, 5, 10 mg COMBINATION THERAPY PERIOD 2 (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication (5mg) to be administered orally according to instructions of Investigator. Ramipril 2.5/5/10 mg: 1 tablet of study medication (2.5mg or 5mg or 10mg) to be administered orally according to instructions of Investigator.
MONOTHERAPY Period 1 RunIn (-4W to W0) STARTED	128	138	0
MONOTHERAPY Period 1 RunIn (-4W to W0) COMPLETED	124	131	0
MONOTHERAPY Period 1 RunIn (-4W to W0) NOT COMPLETED	4	7	0
Combo Period 2 Assessment (W0 to W12) STARTED	0	0	255
Combo Period 2 Assessment (W0 to W12) Completed the Study With Neb 5 mg/ Ram 2.5 mg	0	0	85
Combo Period 2 Assessment (W0 to W12) Completed the Study With Neb 5 mg/ Ram 5 mg	0	0	99
Combo Period 2 Assessment (W0 to W12) Completed the Study With Neb 5 mg/ Ram 10 mg	0	0	71
Combo Period 2 Assessment (W0 to W12) COMPLETED	0	0	255
Combo Period 2 Assessment (W0 to W12) NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Nebivolol 5 mg MONOTHERAPY PERIOD 1 (4 weeks): Eligible patients entered a 4 weeks run-in period (week -4 to week 0) on the same day of the screening visit. Patients previously receiving Neb 5 mg continued the same treatment, while patients receiving any other BBs were switched to Neb 5 mg. Nebivolol 5 mg: 1 tablet of study medication (5mg) to be administered orally according to instructions of Investigator.	Ramipril 5 mg MONOTHERAPY PERIOD 1 (4 weeks): Eligible patients entered a 4 week run-in (week -4 to week 0) period on the same day of the screening visit. Patients previously receiving RAM 5 mg continued the same treatment, while patients receiving any other ACE-i were switched to RAM 5 mg. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Neb 5mg/ Ram 2.5, 5, 10 mg COMBINATION THERAPY PERIOD 2 (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication (5mg) to be administered orally according to instructions of Investigator. Ramipril 2.5/5/10 mg: 1 tablet of study medication (2.5mg or 5mg or 10mg) to be administered orally according to instructions of Investigator.
MONOTHERAPY Period 1 RunIn (-4W to W0) Not compliant with eligibility criteria	3	6	0
MONOTHERAPY Period 1 RunIn (-4W to W0) Lab abnormal results	1	1	0

Baseline Characteristics

Open-label inteRventional Clinical Trial to Assess Efficacy and Safety of the exteMporaneous combInation of Nebivolol and Ramipril in hypertenSIve pAtients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nebivolol 5 mg/Ramipril 2.5 mg n=85 Participants COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients were treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg were up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients continued with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg were up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg were up-titrated to Ramipril 5 mg. Controlled patients continued same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 2.5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 5 mg n=99 Participants COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients were treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg were up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients continued with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg were up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg were up-titrated to Ramipril 5 mg. Controlled patients continued same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 10 mg n=71 Participants COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients were treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg were up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients continued with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg were up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg were up-titrated to Ramipril 5 mg. Controlled patients continued same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 10 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Total n=255 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	63 Participants n=5 Participants	72 Participants n=7 Participants	60 Participants n=5 Participants	195 Participants n=4 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants	27 Participants n=7 Participants	11 Participants n=5 Participants	60 Participants n=4 Participants
Age, Continuous	55.2 years STANDARD_DEVIATION 12.45 • n=5 Participants	55.7 years STANDARD_DEVIATION 13.89 • n=7 Participants	54.0 years STANDARD_DEVIATION 11.59 • n=5 Participants	55.1 years STANDARD_DEVIATION 12.77 • n=4 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	41 Participants n=7 Participants	37 Participants n=5 Participants	133 Participants n=4 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	58 Participants n=7 Participants	34 Participants n=5 Participants	122 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	84 Participants n=5 Participants	98 Participants n=7 Participants	71 Participants n=5 Participants	253 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 12 weeks of combination therapy treatment. From study Visit 2 (Week 0) to study Visit 5 (Week 12)

Population: All pts who signed ICF, met all criteria, received at least one dose of assigned treatment during RunIn, completed RunIn, met criteria at V2 (uncontrolled sitting BP≥130/80 mmHg in pts\<65y old/ BP≥140/80 mmHg in pts≥65 y old atV2, with adequate treatment adherence 80-120%), tolerated treatment, had at least one dose of combination therapy and had at least baseline V2 and V5 assessments with primary efficacy data. 239 pts were included in Modified intention to treat for primary efficacy analysis

Outcome measures

Outcome measures
Measure	Nebivolol 5 mg/Ramipril 2.5/5/10 mg n=239 Participants COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 2.5/5/10 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.
Primary Outcome: Change in Mean Sitting SBP	-19.2 mmHg Standard Deviation 8.62

Adverse Events

Nebivolol 5 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ramipril 5 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Nebivolol 5 mg/Ramipril 2.5 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Nebivolol 5 mg/Ramipril 5 mg

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Nebivolol 5 mg/Ramipril 10 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nebivolol 5 mg n=128 participants at risk MONOTHERAPY PERIOD (4 weeks): Eligible patients entered a 4 weeks run-in period (week -4 to week 0) on the same day of the screening visit. Patients previously receiving Neb 5 mg continued the same treatment, while patients receiving any other BBs were switched to Neb 5 mg. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Ramipril 5 mg n=138 participants at risk MONOTHERAPY PERIOD (4 weeks): Eligible patients entered a 4 week run-in (week -4 to week 0) period on the same day of the screening visit. Patients previously receiving RAM 5 mg continued the same treatment, while patients receiving any other ACE-i were switched to RAM 5 mg. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 2.5 mg n=255 participants at risk COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 2.5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 5 mg n=170 participants at risk COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 10 mg n=71 participants at risk COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 10 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.
Cardiac disorders Arteriospasm coronary	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.

Other adverse events

Other adverse events
Measure	Nebivolol 5 mg n=128 participants at risk MONOTHERAPY PERIOD (4 weeks): Eligible patients entered a 4 weeks run-in period (week -4 to week 0) on the same day of the screening visit. Patients previously receiving Neb 5 mg continued the same treatment, while patients receiving any other BBs were switched to Neb 5 mg. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Ramipril 5 mg n=138 participants at risk MONOTHERAPY PERIOD (4 weeks): Eligible patients entered a 4 week run-in (week -4 to week 0) period on the same day of the screening visit. Patients previously receiving RAM 5 mg continued the same treatment, while patients receiving any other ACE-i were switched to RAM 5 mg. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 2.5 mg n=255 participants at risk COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 2.5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 5 mg n=170 participants at risk COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.	Nebivolol 5 mg/Ramipril 10 mg n=71 participants at risk COMBINATION THERAPY PERIOD (12 weeks): During the Assessment period of 12 weeks (week 0 to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy. Nebivolol 5 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator. Ramipril 10 mg: 1 tablet of study medication to be administered orally according to instructions of Investigator.
Investigations SARS-CoV-2 test positive	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.4% 1/71 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Vascular disorders Hypotension	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Nervous system disorders Headache	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	2.9% 5/170 • Number of events 5 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.4% 1/71 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Nervous system disorders Sciatica	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.2% 2/170 • Number of events 2 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
General disorders Pyrexia	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Gastrointestinal disorders Dyspepsia	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Gastrointestinal disorders Nausea	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.4% 1/71 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Respiratory, thoracic and mediastinal disorders oropharyngeal pain	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.8% 3/170 • Number of events 3 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.4% 1/71 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Influenza	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.6% 4/255 • Number of events 4 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations nasopharyngitis	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.2% 3/255 • Number of events 3 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.8% 3/170 • Number of events 3 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Conjunctivitis	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Pharyngitis	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.39% 1/255 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Sinusitis	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Upper respiratory tract infection	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Bronchitis	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.4% 1/71 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Infections and infestations Covid 19	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/170 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	1.4% 1/71 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.
Metabolism and nutrition disorders Gout	0.00% 0/128 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/138 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/255 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.59% 1/170 • Number of events 1 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.	0.00% 0/71 • From Informed Consent signature at screening visit (Visit 1) occurring 4 week previous than Baseline assessment (Week 0 - Visit 2) to last visit at Week 12 (Visit 5) for an average of 16 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 12 - Visit 5), will be followed for further 2 weeks via a phone call to check about the status of the Adverse Events/Serious Adverse Events, extending the time frame to a total of 18 weeks. Safety Population(SP):All patients(pt) enrolled that received at least one dose of the assigned treatment during RunIn. One pt wasn't dosed wasn't part of SP. If a pt reports the same AE more than once within that System Organ Class SOC/Preferred Term PT, then that pt will be counted only once for that SOC or PT. For the purpose of safety analyses concerning the combination therapy period, 255, 170, and 71 patients were exposed to at least 1 dose of the NEB/RAM 5/2.5 mg,5 mg,10 mg, respectively.

Additional Information

Simone Baldini Global Clinical Operations Manager

A.MENARINI I.F.R SrL

Phone: 055 56801

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place