Trial Outcomes & Findings for An Evaluation of the Safety and Efficacy of Nitazoxanide on Collagen Turnover in NASH Patients With Fibrosis (NCT NCT03656068)

Results Overview

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of treatment-emergent adverse events (TEAEs).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

28 weeks

Results posted on

2022-06-30

Participant Flow

Male and female patients aged from 18 to 75 years, inclusive, at the Screening Visit, with histologically confirmed NASH and fibrosis Stage 2 or 3 were enrolled in the study at a single research center in the United States, at Pinnacle Clinical Research, 5109 Medical Drive, Suite 200 San Antonio, TX 78229.

Potential Subjects who completed all of the Screening Visit assessments and who continued to be eligible for the study, returned to the research center to complete a deuterated water Run-In period. The visit was done on Day -14 +/- 3 days, provided that the subject completed 7 consecutive days of deuterated water administration. Patients returned at Day-11, Day-7 (+/- 1 day) and Day 1 for blood sampling (labelled D2O).

Participant milestones

Participant milestones
Measure	NTZ 500 mg BID Open label group: all patients were to receive study drug Nitazoxanide (Alinia) 500 mg BID for 24 weeks.
Overall Study STARTED	21
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	NTZ 500 mg BID Open label group: all patients were to receive study drug Nitazoxanide (Alinia) 500 mg BID for 24 weeks.
Overall Study Withdrawal by Subject	4
Overall Study Adverse Event	1

Baseline Characteristics

An Evaluation of the Safety and Efficacy of Nitazoxanide on Collagen Turnover in NASH Patients With Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=99 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants
Age, Continuous	55.2 years STANDARD_DEVIATION 11.80 • n=99 Participants
Sex: Female, Male Female	16 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants
Race (NIH/OMB) White	19 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	21 participants n=99 Participants
Height at Screening	164.4 cm STANDARD_DEVIATION 9.17 • n=99 Participants
Baseline weight	94.14 kg STANDARD_DEVIATION 17.793 • n=99 Participants
Baseline body mass index	34.64 kg/m² STANDARD_DEVIATION 4.638 • n=99 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of treatment-emergent adverse events (TEAEs).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) No of participants with at least one TEAE	20 Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) TEAE maximum severity: Grade 1 (mild)	7 Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) TEAE maximum severity: Grade 2 (moderate)	10 Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) TEAE maximum severity: Grade 3 (severe)	3 Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) TEAE maximum severity: Grade 4 (life-threatening)	0 Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) TEAE maximum severity: Grade 5 (death)	0 Participants
Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) No of participants with no TEAE	1 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related treatment-emergent adverse events (TEAEs).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE No of participants with at least 1 treatment-related TEAE	18 Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE TEAE maximum severity: Grade 1 (mild)	10 Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE TEAE maximum severity: Grade 2 (moderate)	8 Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE TEAE maximum severity: Grade 3 (severe)	0 Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE TEAE maximum severity: Grade 4 (life-threatening)	0 Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE TEAE maximum severity: Grade 5 (death)	0 Participants
Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE No of participants with no study drug-related TEAE	3 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of serious adverse events (SAEs).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting Any SAE At least one SAE	4 Participants
Number of NTZ Treated Participants Presenting Any SAE No SAE	17 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related serious adverse events (SAEs).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting Study Drug-Related SAE At least one study-drug related SAE	0 Participants
Number of NTZ Treated Participants Presenting Study Drug-Related SAE No study-drug related SAE	21 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of deaths due to adverse events (AEs).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Deaths Due to AE Yes	0 Participants
Deaths Due to AE No	21 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of adverse events (AEs) leading to withdrawal from study or study drug.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug At least one AE leading to withdrawal	1 Participants
Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug No AE leading to withdrawal	20 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of study drug-related adverse events (AEs) leading to withdrawal from study or study drug

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug At least one study drug-related AE leading to withdrawal	0 Participants
Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug No study drug-related AE leading to withdrawal	21 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by performing clinical laboratory evaluations. Changes in clinical laboratory evaluations were considered clinically significant or not as per Investigator judgment.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations At least one CS change	0 Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations No CS change	21 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by measuring vital signs. Changes in vital signs were considered clinically significant or not as per Investigator judgement

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs At least one CS change	0 Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs No CS change	21 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by performing electrocardiograms (ECGs). Changes in ECGs parameters were considered clinically significant or not as per Investigator judgement.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters No CS change	21 Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters At least one CS change	0 Participants

PRIMARY outcome

Timeframe: 28 weeks

Population: The Safety Analysis Set consisted of all enrolled patients who received at least 1 dose of study drug.

To assess the safety and tolerability of NTZ after 24 weeks of treatment by conducting physical examinations. Changes in physical examinations were considered clinically significant or not as per Investigator judgement.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations At least one CS change	0 Participants
Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations No CS change	21 Participants

SECONDARY outcome

Timeframe: From baseline to end of treatment (Visit 10, Week 24 or early termination)

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

Change in Lumican Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. Lumican is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given "heavy water" to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment	0.0046 pools per day Standard Deviation 0.00924

SECONDARY outcome

Timeframe: From baseline to end of treatment (Visit 10, Week 24 or early termination)

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

Percent Change in Lumican FSR from baseline to end of treatment evaluated through the use of deuterated water. Lumican is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given "heavy water" to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment	15.46 percentage of change Standard Deviation 22.507

SECONDARY outcome

Timeframe: From baseline to end of treatment (Visit 10, Week 24 or early termination)

Change in transforming growth factor beta-induced-protein (TGFBI) Fractional Synthesis Rate (FSR) from baseline to end of treatment evaluated through the use of deuterated water. TGFBI is a marker indicative of hepatic fibrogenesis with its turnover assessed by FSR. This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given "heavy water" to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results were expressed as FSR of these proteins.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment	0.0014 pools per day Standard Deviation 0.01124

SECONDARY outcome

Timeframe: From baseline to end of treatment (Visit 10, Week 24 or early termination)

Percent Change in transforming growth factor beta-induced protein (TGFBI) FSR from baseline to end of treatment evaluated through the use of deuterated water. TGFBI is a marker indicative of hepatic fibrogenesis with its turnover assessed by Fractional Synthesis Rate (FSR). This innovative method of metabolic labelling is based on the concept that liver status could be determined by measuring the ratio of newly synthesized/pre-existing proteins. The turnover rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients were given "heavy water" to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry was used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results were expressed as FSR of these proteins.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment	3.20 percentage of change Standard Deviation 12.619

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The CAP score is a measurement of fatty change in the liver, naming the steatosis grade. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m. 100 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis (steatosis S1), 260 to 290 dB/m indicates moderate steatosis (steatosis S2), and a CAP score greater than 290 dB/m indicates severe steatosis (steatosis S3).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®	-8.1 dB/m Standard Deviation 44.59

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The CAP score is a measurement of fatty change in the liver, naming the steatosis grade.The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m. 100 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis (steatosis S1), 260 to 290 dB/m indicates moderate steatosis (steatosis S2), and a CAP score greater than 290 dB/m indicates severe steatosis (steatosis S3).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®	-1.65 percentage of change Standard Deviation 14.818

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa indicating the abscence of abscence of fibrosis (F0) or a potential fibrosis of stage 1 (F1). The highest possible result is 75 kPa indicating advanced liver fibrosis of stage 4 (F4).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®	0.38 kPa Standard Deviation 4.341

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

FibroScan is a specialized ultrasound machine that measures fibrosis (scarring) and steatosis (fatty change) in the liver. It was required that each subject's FibroScan® assessments be done with the same type of probe at each study visit. The fibrosis result is measured in kilopascals (kPa) It's normally between 2 and 6 kPa indicating the abscence of abscence of fibrosis (F0) or a potential fibrosis of stage 1 (F1). The highest possible result is 75 kPa indicating advanced liver fibrosis of stage 4 (F4).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®	8.77 percentage of change Standard Deviation 39.828

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 13 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=13 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)	-0.12 kPa Standard Deviation 0.731

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 13 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=13 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)	-1.89 percentage of change Standard Deviation 17.807

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 12 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=12 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)	-0.35 kPa Standard Deviation 0.581

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 12 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Liver stiffness was assessed by MRE. It was recommended that each subject's radiological assessment was performed using the same procedure for each study visit.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=12 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)	-6.61 percentage of change Standard Deviation 15.029

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Alpha-2 Macroglobulin From Baseline to Week 12	-11.0 mg/dL Interval -94.0 to 56.0

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12	-5.64 percentage of change Interval -20.0 to 27.3

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Alpha-2 Macroglobulin From Baseline to End of Treatment	-9.0 mg/dL Interval -70.0 to 42.0

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment	-4.85 percentage of change Interval -16.0 to 22.6

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Fibroblast Growth Factor 19 From Baseline to Week 12	28.0 ng/L Interval -155.0 to 282.0

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12	38.74 percentage of change Interval -68.9 to 361.1

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment	24.0 ng/L Interval -377.0 to 290.0

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment	42.11 percentage of change Interval -81.1 to 637.8

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Fibroblast Growth Factor 21 From Baseline to Week 12	2.40 ng/L Interval -1609.8 to 1009.8

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12	0.36 percentage of change Interval -68.6 to 504.6

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment	-102.90 ng/L Interval -1728.6 to 928.9

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment	-15.36 percentage of change Interval -56.8 to 511.8

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Human Chitinase 3-like 1 From Baseline to Week 12	5423.0 ng/L Interval -180529.0 to 91341.0

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12	8.90 percentage of change Interval -54.0 to 106.6

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Human Chitinase 3-like 1 From Baseline to End of Treatment	5338.0 ng/L Interval -102066.0 to 121135.0

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment	8.76 percentage of change Interval -36.8 to 74.9

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Hyaluronic Acid From Baseline to Week 12	6.210 µg/L Interval -22.12 to 323.24

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Hyaluronic Acid From Baseline to Week 12	10.93 percentage of change Interval -41.1 to 199.3

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Hyaluronic Acid From Baseline to End of Treatment	6.100 µg/L Interval -26.83 to 235.19

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Hyaluronic Acid From Baseline to End of Treatment	6.99 percentage of change Interval -46.2 to 202.2

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12	-0.160 score Interval -0.67 to 1.25

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12	-1.64 percentage of change Interval -7.3 to 11.5

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=16 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment	0.090 score Interval -0.89 to 1.32

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples. ELF score is a continuous (not a categorical) variable with \< 9.8 indicative of low risk of progression to cirrhosis and \>=9.8 to \>11.3 indicative of mid-risk and \>=11.30 indicative of higher risk.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=16 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment	0.90 percentage of change Interval -9.7 to 12.0

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in M30 From Baseline to Week 12	0.000 U/L Interval -500.92 to 740.29

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in M30 Biomarker From Baseline to Week 12	0.00 percentage of change Interval -59.7 to 89.2

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in M30 Biomarker From Baseline to End of Treatment	-34.920 U/L Interval -602.5 to 853.74

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in M30 Biomarker From Baseline to End of Treatment	-5.48 percentage of change Interval -63.9 to 113.0

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in M65 Biomarker From Baseline to Week 12	-15.605 U/L Interval -1100.35 to 801.43

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in M65 Biomarker From Baseline to Week 12	-3.52 percentage of change Interval -90.7 to 144.2

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in M65 Biomarker From Baseline to End of Treatment	-58.970 U/L Interval -1098.6 to 839.44

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in M65 Biomarker From Baseline to End of Treatment	-11.56 percentage of change Interval -84.6 to 213.2

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=16 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in miR34a Fold From Baseline to Week 12	-0.0991 fold change Interval -4.331 to 2.033

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=16 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in miR34a Fold From Baseline to Week 12	-7.42 percentage of change Interval -66.3 to 213.8

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=16 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in miR34a Fold From Baseline to End of Treatment	-0.5019 fold change Interval -3.561 to 3.181

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 16 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=16 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in miR34a Fold From Baseline to End of Treatment	-24.90 percentage of change Interval -78.1 to 308.4

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Pro-C3 From Baseline to Week 12	-0.80 µg/L Interval -8.0 to 10.8

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Pro-C3 From Baseline to Week 12	-2.80 percentage of change Interval -28.7 to 59.3

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Pro-C3 From Baseline to End of Treatment	-2.60 µg/L Interval -14.8 to 6.3

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Pro-C3 From Baseline to End of Treatment	-12.70 percentage of change Interval -42.5 to 34.6

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Pro-C6 From Baseline to Week 12	0.40 µg/L Interval -2.6 to 9.6

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Pro-C6 From Baseline to Week 12	1.98 percentage of change Interval -14.4 to 36.2

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Pro-C6 From Baseline to End of Treatment	-0.20 µg/L Interval -4.4 to 3.9

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Pro-C6 From Baseline to End of Treatment	-0.75 percentage of change Interval -24.3 to 24.5

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12	-1.560 µg/L Interval -4.46 to 5.38

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12	-9.73 percentage of change Interval -33.5 to 34.9

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment	0.180 µg/L Interval -5.22 to 11.83

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment	1.22 percentage of change Interval -42.9 to 59.1

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12	10.50 µg/L Interval -133.2 to 177.5

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). 21 patients were analyzed for this Outcome Measure, as all patients had a result both at baseline and at the week 12 visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=21 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12	3.53 percentage of change Interval -21.1 to 38.0

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment	13.40 µg/L Interval -36.6 to 67.4

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 17 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Non-invasive Fibrosis Biomarkers were assessed in blood samples.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=17 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment	3.78 percentage of change Interval -16.6 to 27.6

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12	-0.3665 score Standard Deviation 0.77812

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12	16.64 percentage of change Standard Deviation 136.529

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=8 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment	-0.2679 score Standard Deviation 0.43795

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

NAFLD NFS : \< -1.5 for low probability of fibrosis, \> -1.5 to \< 0.67 for intermediate probability of fibrosis, and \> 0.67 for high probability of fibrosis.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=8 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment	15.02 percentage of change Standard Deviation 74.847

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Fibrosis-4 Score From Baseline to Week 12	-0.18 score Standard Deviation 0.516

SECONDARY outcome

Timeframe: 12 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 20 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the week 12 visit.

Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=20 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Fibrosis-4 Score From Baseline to Week 12	-11.53 percentage of change Standard Deviation 34.342

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=8 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Change in Fibrosis-4 Score From Baseline to End of Treatment	-0.12 score Standard Deviation 0.328

SECONDARY outcome

Timeframe: 24 weeks

Population: The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1). There were 8 patients analyzed for this Outcome Measure, corresponding to the patients having a result both at baseline and at the end of treatment visit.

Fibrosis-4 score : FIB4 \< 1.3 is not consistent with F3-F6 disease. FIB4 of 1.3 to \<2.67 is indeterminate for F3-F6 disease. \> 2.67 is consistent F3 to F6.

Outcome measures

Outcome measures
Measure	NTZ 500 mg BID n=8 Participants Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Percent Change in Fibrosis-4 Score From Baseline to End of Treatment	-8.02 percentage of change Standard Deviation 17.754

Adverse Events

NTZ 500 mg BID

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	NTZ 500 mg BID n=21 participants at risk Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Renal and urinary disorders Nephrolithiasis	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Reproductive system and breast disorders Menometrorrhagia	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Musculoskeletal and connective tissue disorders Lumbar Spinal Stenosis	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Cardiac disorders Atrial Fibrillation	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Cardiac disorders Angina Unstable	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Cardiac disorders Coronary Artery Disease	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Cardiac disorders cardiac failure	4.8% 1/21 • Number of events 1 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.

Other adverse events

Other adverse events
Measure	NTZ 500 mg BID n=21 participants at risk Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Gastrointestinal disorders Diarrhoea	23.8% 5/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Abdominal pain	14.3% 3/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Nausea	14.3% 3/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Abdominal pain upper	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Constipation	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Gastric ulcer	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Abdominal discomfort	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Abdominal distension	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Anorectal discomfort	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Dyspepsia	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Gastrointestinal pain	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Large intestine polyp	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Pancreatic cyst	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Gastrointestinal disorders Toothache	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Urinary tract infection	23.8% 5/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Gastroenteritis viral	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Bronchitis	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Fungal skin infection	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Influenza	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Nasopharyngitis	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Infections and infestations Tinea pedis	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Renal and urinary disorders Chromaturia	33.3% 7/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Renal and urinary disorders Ureterolithiasis	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Blood cholesterol increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Blood creatine phosphokinase increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Blood creatinine increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Blood glucose increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Glomerular filtration rate increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Glycosylated haemoglobin increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Heart rate increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Norovirus test positive	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Investigations Weight increased	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Metabolism and nutrition disorders Decreased appetite	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Metabolism and nutrition disorders Diabetes mellitus	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Metabolism and nutrition disorders Hypertryglyceridaemia	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Metabolism and nutrition disorders Type 2 diabetes mellitus	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Musculoskeletal and connective tissue disorders Muscle spasm	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Musculoskeletal and connective tissue disorders Back pain	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Musculoskeletal and connective tissue disorders Joint effusion	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Musculoskeletal and connective tissue disorders Myalgia	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Nervous system disorders Headache	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Nervous system disorders Dizziness	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Nervous system disorders Hepatic encephalopathy	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Nervous system disorders Hypoaesthesia	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Injury, poisoning and procedural complications fall	14.3% 3/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Injury, poisoning and procedural complications Arthropod sting	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Injury, poisoning and procedural complications Procedural pain	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
General disorders Pain	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
General disorders Fatigue	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Skin and subcutaneous tissue disorders Pruritus	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Skin and subcutaneous tissue disorders Alopecia	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Blood and lymphatic system disorders Anaemia	9.5% 2/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Blood and lymphatic system disorders Splenomegaly	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Hepatobiliary disorders Cholelithiasis	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Hepatobiliary disorders Hepatic cirrhosis	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Hepatobiliary disorders Portal hypertension	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Reproductive system and breast disorders Ovarian cyst	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Eye disorders Vision blurred	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Immune system disorders Seasonal allergy	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.
Psychiatric disorders Anxiety	4.8% 1/21 • from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration. All AEs regardless of seriousness or relationship to study drug, including those occurring during the Screening Period, were recorded in the eCRF from ICF signature until study end for each patient. Whenever possible, symptoms were grouped as a single syndrome or diagnosis. The Investigator established whether or not any AE occurred at each visit from the date of consent. The patient was questioned in a general manner without offering the patient any suggestion.

Additional Information

Stephen Harrison, MD

Pinnacle Clinical Research

Phone: 210-982-0320

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place