Trial Outcomes & Findings for Effectiveness and Safety of Combination of Amlodipine and Zofenopril in Hypertensive Patients Versus Each Monotherapy (NCT NCT05279807)

Last Updated: 2024-10-21

Results Overview

To assess the antihypertensive efficacy of the extemporaneous combination of Zofenopril (ZOF) 30 mg in combination with Amlodipine (AML) 5 mg or AML 10 mg in lowering the sitting diastolic BP between Visit 2 (Week 0) and Visit 4 (Week 8) in patients with uncontrolled BP previously treated with Zofenopril or Amlodipine (5 mg) monotherapies for at least 4 weeks during run-in period.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

277 participants

Primary outcome timeframe

From Visit 2 (week 0) to Visit 4 (week 8) for a total of 8 weeks

Results posted on

2024-10-21

Participant Flow

After Screening visit, eligible patients entered a 4 week run-in period (from week -4 to week 0) on the same day of the screening visit. Patients previously receiving ZOF 30 mg or AML 5 mg continued the same treatment, patients receiving any other angiotensin converting enzyme inhibitors, were switched to ZOF 30 mg, while patients receiving calcium channel blockers received AML 5 mg. Assessment period starts from week 0 (baseline) till week 8 for a total of 8 weeks

Participant milestones

Participant milestones
Measure	Zofenopril 30mg MONOTHERAPY PERIOD (4 weeks): patients will be treated with Zofenopril 30 mg during the Run In period (week -4 to week 0) COMBINATION THERAPY PERIOD: During the Assessment period of 8 weeks (week 0 - week 8) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy during the Assessment Period (week 0 - week 4). Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.	Amlodipine 5/10 mg MONOTHERAPY PERIOD (4 weeks): patients will be treated with Amlodipine 5 mg during the Run In period (week -4 to week 0) COMBINATION THERAPY PERIOD: During the Assessment period of 8 weeks (week 0 - week 8) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.
Overall Study STARTED	144	133
Overall Study COMPLETED	142	132
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Zofenopril 30mg MONOTHERAPY PERIOD (4 weeks): patients will be treated with Zofenopril 30 mg during the Run In period (week -4 to week 0) COMBINATION THERAPY PERIOD: During the Assessment period of 8 weeks (week 0 - week 8) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy during the Assessment Period (week 0 - week 4). Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.	Amlodipine 5/10 mg MONOTHERAPY PERIOD (4 weeks): patients will be treated with Amlodipine 5 mg during the Run In period (week -4 to week 0) COMBINATION THERAPY PERIOD: During the Assessment period of 8 weeks (week 0 - week 8) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	0	1
Overall Study Laboratory Abnormal Results	1	0

Baseline Characteristics

Effectiveness and Safety of Combination of Amlodipine and Zofenopril in Hypertensive Patients Versus Each Monotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zofenopril 30mg n=144 Participants MONOTHERAPY PERIOD (4 weeks): patients will be treated with Zofenopril30 mg during the Run In period (week -4 to week 0) COMBINATION THERAPY PERIOD: During the Assessment period of 8 weeks (week 0 - week 8) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.	Amlodipine 5/10 mg n=133 Participants MONOTHERAPY PERIOD (4 weeks): patients will be treated with Amlodipine 5 mg. COMBINATION THERAPY PERIOD: During the Assessment period of 8 weeks (week0 - week 8) uncontrolled patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks. Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.	Total n=277 Participants Total of all reporting groups
Age, Continuous	51.1 years STANDARD_DEVIATION 9.96 • n=5 Participants	54.1 years STANDARD_DEVIATION 9.03 • n=7 Participants	52.3 years STANDARD_DEVIATION 9.83 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	83 Participants n=7 Participants	160 Participants n=5 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	50 Participants n=7 Participants	117 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	144 Participants n=5 Participants	133 Participants n=7 Participants	277 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Visit 2 (week 0) to Visit 4 (week 8) for a total of 8 weeks

Population: Efficacy Population: all study participants who signed inform consent, met all screening criteria, were enrolled and received at least one dose of the assigned treatment during the run-in period and completed the 4-week run-in period, who met criteria at Visit 2 (Week 0) \[uncontrolled BP (sitting Systolic BP/DBP \> 130 / 80 mmHg)\], tolerated treatment, had treatment adherence between 80 - 120 % and had at least one available post baseline primary efficacy assessment.

Outcome measures

Outcome measures
Measure	Combination Therapy Phase Zofenopril 30mg/Amlodipine 5 or 10 mg n=269 Participants Combination Therapy Phase (8 weeks) from Visit 2 (week 0) to Visit 4 (week 8): uncontrolled patients with Monotherapy (Zofenopril 30mg or Amlodipine 5 mg) are treated with the extemporaneous combination of Zofenopril 30mg and Amlodipine 5mg for 4 weeks. Amlodipine10mg will replace Amlodipine 5mg in uncontrolled patients for further 4 weeks while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator. Amlodipine: Tablets of 5mg and 10mg administered orally once daily according instructions provided by Principal Investigator.
Change in Mean Sitting Diastolic Blood Pressure (DBP) Between Visit 2 (Week 0) and Visit 4 (Week 8)	-13.5 mmHg Standard Deviation 8.31

Adverse Events

Zofenopril 30mg MONOTHERAPY PERIOD

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Amlodipine 5 mg MONOTHERAPY PERIOD

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Zofenopril 30mg/Amlodipine 5mg COMBINATION THERAPY PERIOD

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Zofenopril 30mg/Amlodipine 10mg COMBINATION THERAPY PERIOD

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zofenopril 30mg MONOTHERAPY PERIOD n=143 participants at risk Patients will be treated with Zofenopril 30 mg during the Run in Period (week -4 to week 0). Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator.	Amlodipine 5 mg MONOTHERAPY PERIOD n=133 participants at risk Patients will be treated with Amlodipine 5 mg during the Run in Period (week -4 to week 0). Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator.	Zofenopril 30mg/Amlodipine 5mg COMBINATION THERAPY PERIOD n=149 participants at risk Uncontrolled patients at week 0 will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks during the Assessment Period (week 0 - week 4). Amlodipine: Tablets of 5mg administered orally once daily according instructions provided by Principal Investigator.	Zofenopril 30mg/Amlodipine 10mg COMBINATION THERAPY PERIOD n=122 participants at risk Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients at week 4 (Visit 3) during the Assessment Period for further 4 weeks (week 4 - week 8) while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Amlodipine: Tablets of 10mg administered orally once daily according instructions provided by Principal Investigator.
Gastrointestinal disorders Oesophageal food impaction	0.00% 0/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.82% 1/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term

Other adverse events

Other adverse events
Measure	Zofenopril 30mg MONOTHERAPY PERIOD n=143 participants at risk Patients will be treated with Zofenopril 30 mg during the Run in Period (week -4 to week 0). Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator.	Amlodipine 5 mg MONOTHERAPY PERIOD n=133 participants at risk Patients will be treated with Amlodipine 5 mg during the Run in Period (week -4 to week 0). Zofenopril: Film-Coated tablets administered orally once daily according instructions provided by Principal Investigator.	Zofenopril 30mg/Amlodipine 5mg COMBINATION THERAPY PERIOD n=149 participants at risk Uncontrolled patients at week 0 will be treated with the extemporaneous combination of Zofenopril 30 mg and Amlodipine 5mg for 4 weeks during the Assessment Period (week 0 - week 4). Amlodipine: Tablets of 5mg administered orally once daily according instructions provided by Principal Investigator.	Zofenopril 30mg/Amlodipine 10mg COMBINATION THERAPY PERIOD n=122 participants at risk Amlodipine 10mg will replace Amlodipine 5mg in uncontrolled patients at week 4 (Visit 3) during the Assessment Period for further 4 weeks (week 4 - week 8) while controlled patients with Zofenopril 30mg/Amlodipine 5mg will continue with the same therapy. Amlodipine: Tablets of 10mg administered orally once daily according instructions provided by Principal Investigator.
Gastrointestinal disorders Dry Mouth	0.00% 0/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.5% 2/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
General disorders Asthenia	0.70% 1/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.5% 2/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Infections and infestations COVID-19	0.70% 1/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	3.0% 4/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	3.3% 4/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Nervous system disorders Dizziness	1.4% 2/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.67% 1/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Nervous system disorders Headache	2.1% 3/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.5% 2/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.67% 1/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	3.3% 4/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Infections and infestations Respiratory tract infection viral	0.70% 1/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.75% 1/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	4.0% 6/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.6% 2/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.67% 1/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.6% 2/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.67% 1/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	3.3% 4/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Gastrointestinal disorders Gastritis	0.00% 0/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.6% 2/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term
Gastrointestinal disorders Nausea	0.00% 0/143 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/133 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	0.00% 0/149 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term	1.6% 2/122 • 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 8 (Visit 4) for an average of 12 weeks. Furthermore patients having any ongoing Adverse Event/Serious Adverse Event at the end of the treatment (Week 8 - Visit 4), 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 14 weeks. Safety Population (used for safety analyses): "All study participants enrolled that received at least one dose of the assigned treatment during the run-in period". One Enrolled patient was not dosed and therefore was not part of Safety Population. If a patient reports the same Adverse Event (AE) more than once within that System Organ Class/Preferred Term, then that patient will be counted only once for that System Organ Class or Preferred Term

Additional Information

Clinical Operation Director

A. Menarini Industrie Farmaceutiche Riunite SrL

Phone: +39 055 5680459

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60