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

• Sponsor: Pinnacle Clinical Research, PLLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT03656068
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Actual Duration (Months): 23.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability of Nitazoxanide (NTZ) 500mg Twice Daily (BID) after 24 weeks of treatment in patients with NASH induced Stage 2 or Stage 3 fibrosis

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Steatohepatitis; Fatty Liver; Fibrosis, Liver; Compensated Cirrhosis	Drug: Nitazoxanide 500mg BID	Phase 2

Detailed Description

Based on the anti-fibrotic properties demonstrated in the animal models of fibrosis, this proof of concept clinical study aims at evaluating NTZ in patients with non-alcoholic steatohepatitis (NASH) and fibrosis stage 2 and 3. Although NTZ has been evaluated in liver disease populations up to 60 weeks, this is the first study evaluating NTZ treatment in a population with NASH induced stage 2 and 3 fibrosis. The aim of this study is to evaluate the safety and tolerability of NTZ 500 mg BID after 24 weeks of treatment in this population.

This proof of concept study will also evaluate the anti-fibrotic effect of NTZ as a secondary objective.

The methods of evaluation of fibrosis will include an innovative method of metabolic labeling.This approach is based on the concept that liver status can be determined by measuring the ratio of newly synthesized/pre-existing proteins.The turn-over rate of newly synthesized collagen and proteins represents the hepatic fibrogenic disease activity. Patients will be given "heavy water" to drink. Heavy water contains D20, deuterium being a stable isotope of hydrogen. Mass spectrometry is used to identify individual proteins and to quantify the ratio of labeled protein to total protein. The results are expressed as fractional synthesis rate of these proteins (FSR). This method has been previously published (Decaris et al, 2017).

Other non-invasive methods will be used to evaluate the liver stiffness changes after NTZ treatment: Magnetic Resonance Elastography (MRE) and FibroScan®.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Monocentric, Open-Label, Proof of Concept Study to Evaluate the Safety and Efficacy of Nitazoxanide at 500mg Twice Daily on Collagen Turnover in Plasma in NASH Patients With Fibrosis Stage 2 or 3
• Actual Study Start Date: Dec 4, 2018
• Actual Primary Completion Date: Nov 25, 2020
• Actual Study Completion Date: Nov 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open label NTZ Open label. All patients will receive study drug	Drug: Nitazoxanide 500mg BID; Patients will receive 500mg of Nitazoxanide BID daily for 24 weeks; Other Names: NTZ

Outcome Measures

Primary Outcome Measures

1. Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE) [28 weeks]

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

2. Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE [28 weeks]

   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).

3. Number of NTZ Treated Participants Presenting Any SAE [28 weeks]

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

4. Number of NTZ Treated Participants Presenting Study Drug-Related SAE [28 weeks]

   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).

5. Deaths Due to AE [28 weeks]

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

6. Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug [28 weeks]

   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.

7. Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug [28 weeks]

   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

8. Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations [28 weeks]

   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.

9. Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs [28 weeks]

   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

10. Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters [28 weeks]

    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.

11. Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations [28 weeks]

    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.

Secondary Outcome Measures

1. Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment [From baseline to end of treatment (Visit 10, Week 24 or early termination)]

   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.

2. Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment [From baseline to end of treatment (Visit 10, Week 24 or early termination)]

   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.

3. Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment [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.

4. Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment [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.

5. Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan® [24 weeks]

   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).

6. Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan® [24 weeks]

   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).

7. Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan® [24 weeks]

   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).

8. Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan® [24 weeks]

   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).

9. Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE) [12 weeks]

   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.

10. Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE) [12 weeks]

    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.

11. Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE) [24 weeks]

    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.

12. Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE) [24 weeks]

    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.

13. Change in Alpha-2 Macroglobulin From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

14. Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

15. Change in Alpha-2 Macroglobulin From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

16. Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

17. Change in Fibroblast Growth Factor 19 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

18. Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

19. Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

20. Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

21. Change in Fibroblast Growth Factor 21 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

22. Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

23. Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

24. Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

25. Change in Human Chitinase 3-like 1 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

26. Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

27. Change in Human Chitinase 3-like 1 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

28. Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

29. Change in Hyaluronic Acid From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

30. Percent Change in Hyaluronic Acid From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

31. Change in Hyaluronic Acid From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

32. Percent Change in Hyaluronic Acid From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

33. Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12 [12 weeks]

    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

34. Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12 [12 weeks]

    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.

35. Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment [24 weeks]

    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.

36. Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment [24 weeks]

    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.

37. Change in M30 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

38. Percent Change in M30 Biomarker From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

39. Change in M30 Biomarker From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

40. Percent Change in M30 Biomarker From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

41. Change in M65 Biomarker From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

42. Percent Change in M65 Biomarker From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

43. Change in M65 Biomarker From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

44. Percent Change in M65 Biomarker From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

45. Change in miR34a Fold From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

46. Percent Change in miR34a Fold From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

47. Change in miR34a Fold From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

48. Percent Change in miR34a Fold From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

49. Change in Pro-C3 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

50. Percent Change in Pro-C3 From Baseline to Week 12 [12 weeks]

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

51. Change in Pro-C3 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

52. Percent Change in Pro-C3 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

53. Change in Pro-C6 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

54. Percent Change in Pro-C6 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

55. Change in Pro-C6 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

56. Percent Change in Pro-C6 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

57. Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

58. Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

59. Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

60. Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

61. Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

62. Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12 [12 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

63. Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

64. Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment [24 weeks]

    Non-invasive Fibrosis Biomarkers were assessed in blood samples.

65. Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12 [12 weeks]

    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.

66. Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12 [12 weeks]

    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.

67. Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment [24 weeks]

    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.

68. Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment [24 weeks]

    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.

69. Change in Fibrosis-4 Score From Baseline to Week 12 [12 weeks]

    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.

70. Percent Change in Fibrosis-4 Score From Baseline to Week 12 [12 weeks]

    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.

71. Change in Fibrosis-4 Score From Baseline to End of Treatment [24 weeks]

    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.

72. Percent Change in Fibrosis-4 Score From Baseline to End of Treatment [24 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or females aged from 18 to 75 years inclusive the Screening Visit.

2. Must provide signed written informed consent and agree to comply with the study protocol.

3. Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study

4. Histological confirmation of steatohepatitis on a diagnostic liver biopsy (biopsy obtained within 6 months prior to Screening or during the Screening Period) with at least 1 in each component of the NAS (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).

5. Fibrosis stage of 2 or 3, according to the NASH Clinical Research Network fibrosis staging system on a diagnostic liver biopsy (biopsy obtained within 6 months prior to Screening or during the Screening Period).

6. Two assessments of ALT, AST, Total bilirubin, Alkaline phosphatase (ALP), Creatine phosphokinase (CPK) will be collected during screening at least 4 weeks apart. To be eligible the second value cannot be ≥2x the first value.

Exclusion Criteria:

1. History of efficient bariatric surgery within 5 years prior to Screening, or planned bariatric surgery in the course of the study.

2. Patients with HbA1c >10.0%. If abnormal at the first Screening Visit, the HbA1c measurement can be repeated. A repeated abnormal HbA1c (HbA1c >10.0%) leads to exclusion.

3. Patients with a history of clinically significant acute cardiac event within 6 months prior to Screening such as: stroke, transient ischemic attack, or coronary heart disease (angina pectoris, myocardial infarction, revascularization procedures).

4. Weight loss of more than 10% within 6 months prior to Randomization.

5. Patient with any history or presence of decompensated cirrhosis.

6. Current or recent history (<1 year) of significant alcohol consumption. For men, significant consumption is typically defined as higher than 30 g pure alcohol per day. For women, it is typically defined as higher than 20 g pure alcohol per day.

7. Current or history of other substance abuse within 1 year prior to screening.

8. Pregnant or lactating females or females planning to become pregnant during the study period.

9. Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not restricted to:

10. Positive hepatitis B surface antigen (HBsAg)

11. Positive Hepatitis C virus (HCV) RNA, (tested for in case of known cured HCV infection, or positive HCV Ab at Screening)

12. Suspicion of drug-induced liver disease

13. Alcoholic liver disease

14. Autoimmune hepatitis

15. Wilson's disease

16. Primary biliary cirrhosis, primary sclerosing cholangitis

17. Genetic homozygous hemochromatosis

18. Known or suspected Hepatocellular Carcinoma

19. History or planned liver transplant, or current Model for End-Stage Liver Disease score >15.

20. Patients who cannot be contacted in case of emergency.

21. Known hypersensitivity to the investigation product or any of its formulation excipients.

22. Patients who are taking warfarin or other highly plasma protein-bound drugs with narrow therapeutic indices.

23. Patients who are currently participating in, plan to participate in, or have participated in an investigational drug trial or medical device trial containing active substance within 30 days or five half-lives, whichever is longer, prior to Screening.

24. Evidence of any other unstable or, untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic, or psychiatric disease.

25. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.

26. History of noncompliance with medical regimens, or patients who are considered to be unreliable.

27. Positive anti-human immunodeficiency virus (HIV) antibody.

28. AST and/or ALT >10 x upper limit of normal (ULN).

29. Total bilirubin >1.3 mg/dL due to altered hepatic function.

30. Direct bilirubin > ULN Note: Gilbert Disease patients are allowed into the study.

31. International Normalized Ratio >1.2 in the absence of anticoagulant therapy.

32. Platelet count <150,000/mm3 in the context of portal hypertension.

33. Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate of less than 60 ml/min/1.73 m2).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Clinical Research	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Pinnacle Clinical Research, PLLC

Investigators

• Principal Investigator: Stephen Harrison, MD, Pinnacle Clinical Research

Study Documents (Full-Text)

• Study Protocol: V27AUG2018 - Aug 27, 2018
• Study Protocol: V21OCT2018 - Oct 21, 2018
• Study Protocol: V02MAR2019 - Mar 2, 2019
• Study Protocol: V24AUG2019 - Aug 24, 2019
• Study Protocol: 26FEB2020 - Feb 26, 2020
• Study Protocol: V15APR2020 - Apr 15, 2020
• Statistical Analysis Plan: V1.0 - Apr 30, 2019
• Statistical Analysis Plan: V1.1 - Apr 9, 2020

More Information

Publications

None provided.

• Responsible Party: Stephen A. Harrison, Principal Investigator, Pinnacle Clinical Research, PLLC
• ClinicalTrials.gov Identifier: NCT03656068
• Other Study ID Numbers: NTZ-218-1
• First Posted: Sep 4, 2018
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Fibrosis; Nitazoxanide

Study Results

Participant Flow

Recruitment Details

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.

Pre-assignment Detail

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).

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide (Alinia) 500 mg BID for 24 weeks.
Period Title: Overall Study
STARTED	21
COMPLETED	16
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 81%
>=65 years	4 19%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.2 (11.80)
Sex: Female, Male (Count of Participants)
Female	16 76.2%
Male	5 23.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 61.9%
Not Hispanic or Latino	8 38.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 4.8%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.8%
White	19 90.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	21 100%
Height at Screening (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	164.4 (9.17)
Baseline weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	94.14 (17.793)
Baseline body mass index (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	34.64 (4.638)

Outcome Measures

1. Primary Outcome

Title	Number of NTZ Treated Participants Presenting Any Treatment Emergent Adverse Event (TEAE)
Description	To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of treatment-emergent adverse events (TEAEs).
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
No of participants with at least one TEAE	20 95.2%
TEAE maximum severity: Grade 1 (mild)	7 33.3%
TEAE maximum severity: Grade 2 (moderate)	10 47.6%
TEAE maximum severity: Grade 3 (severe)	3 14.3%
TEAE maximum severity: Grade 4 (life-threatening)	0 0%
TEAE maximum severity: Grade 5 (death)	0 0%
No of participants with no TEAE	1 4.8%

2. Primary Outcome

Title	Number of NTZ Treated Participants Presenting Any Study Drug Related TEAE
Description	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).
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
No of participants with at least 1 treatment-related TEAE	18 85.7%
TEAE maximum severity: Grade 1 (mild)	10 47.6%
TEAE maximum severity: Grade 2 (moderate)	8 38.1%
TEAE maximum severity: Grade 3 (severe)	0 0%
TEAE maximum severity: Grade 4 (life-threatening)	0 0%
TEAE maximum severity: Grade 5 (death)	0 0%
No of participants with no study drug-related TEAE	3 14.3%

3. Primary Outcome

Title	Number of NTZ Treated Participants Presenting Any SAE
Description	To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of serious adverse events (SAEs).
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one SAE	4 19%
No SAE	17 81%

4. Primary Outcome

Title	Number of NTZ Treated Participants Presenting Study Drug-Related SAE
Description	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).
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one study-drug related SAE	0 0%
No study-drug related SAE	21 100%

5. Primary Outcome

Title	Deaths Due to AE
Description	To assess the safety and tolerability of NTZ after 24 weeks of treatment by assessing the occurrence of deaths due to adverse events (AEs).
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Yes	0 0%
No	21 100%

6. Primary Outcome

Title	Number of NTZ Treated Participants Presenting Any AE Leading to Withdrawal From Study or Study Drug
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one AE leading to withdrawal	1 4.8%
No AE leading to withdrawal	20 95.2%

7. Primary Outcome

Title	Number of NTZ Treated Participants Presenting Any Study Drug-related AE Leading to Withdrawal From Study or Study Drug
Description	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
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one study drug-related AE leading to withdrawal	0 0%
No study drug-related AE leading to withdrawal	21 100%

8. Primary Outcome

Title	Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Clinical Laboratory Evaluations
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one CS change	0 0%
No CS change	21 100%

9. Primary Outcome

Title	Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Vital Signs
Description	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
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one CS change	0 0%
No CS change	21 100%

10. Primary Outcome

Title	Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Electrocardiogram Parameters
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one CS change	0 0%
No CS change	21 100%

11. Primary Outcome

Title	Number of NTZ Treated Participants Presenting at Least One Clinically Significant (CS) Change in Physical Examinations
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
At least one CS change	0 0%
No CS change	21 100%

12. Secondary Outcome

Title	Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment
Description	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.
Time Frame	From baseline to end of treatment (Visit 10, Week 24 or early termination)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [pools per day]	0.0046 (0.00924)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Wilcoxon signed-rank test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0039
	Comments	p-value for testing median = 0
	Method	Sign test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	0.0030
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percent Change in Lumican Fractional Synthesis Rate (FSR) From Baseline to End of Treatment
Description	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.
Time Frame	From baseline to end of treatment (Visit 10, Week 24 or early termination)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [percentage of change]	15.46 (22.507)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Wilcoxon signed-rank test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0026
	Comments	p-value for testing median = 0
	Method	Sign test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	10.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment
Description	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.
Time Frame	From baseline to end of treatment (Visit 10, Week 24 or early termination)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [pools per day]	0.0014 (0.01124)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Wilcoxon signed-rank test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.5555
	Comments	p-value for testing median = 0
	Method	Sign test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	0.0020
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percent Change in Transforming Growth Factor Beta-induced Protein (TGFBI) FSR From Baseline to End of Treatment
Description	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.
Time Frame	From baseline to end of treatment (Visit 10, Week 24 or early termination)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [percentage of change]	3.20 (12.619)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Wilcoxon signed-rank test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3778
	Comments	p-value for testing median = 0
	Method	Sign test
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	1.72
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®
Description	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).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [dB/m]	-8.1 (44.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.4638
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.1
	Confidence Interval	(2-Sided) 95%; -31.0 to 14.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Percent Change in Controlled Attenuation Parameter (CAP) Score From Baseline to End of Treatment as Evaluated by FibroScan®
Description	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).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [percentage of change]	-1.65 (14.818)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.6532
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.65
	Confidence Interval	(2-Sided) 95%; -9.26 to 5.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®
Description	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).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [kPa]	0.38 (4.341)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7254
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -1.86 to 2.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated by FibroScan®
Description	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).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Mean (Standard Deviation) [percentage of change]	8.77 (39.828)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3772
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.77
	Confidence Interval	(2-Sided) 95%; -11.70 to 29.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	13
Mean (Standard Deviation) [kPa]	-0.12 (0.731)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.5799
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Percent Change in Liver Stiffness From Baseline to Week 12 as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	13
Mean (Standard Deviation) [percentage of change]	-1.89 (17.807)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7088
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.89
	Confidence Interval	(2-Sided) 95%; -12.65 to 8.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	12
Mean (Standard Deviation) [kPa]	-0.35 (0.581)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0609
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.72 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Percent Change in Liver Stiffness From Baseline to End of Treatment as Evaluated Through the Use Magnetic Resonance Elastography (MRE)
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	12
Mean (Standard Deviation) [percentage of change]	-6.61 (15.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1556
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.61
	Confidence Interval	(2-Sided) 95%; -16.16 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Change in Alpha-2 Macroglobulin From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [mg/dL]	-11.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0709
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-14.6
	Confidence Interval	(2-Sided) 95%; -30.6 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Percent Change in Alpha-2 Macroglobulin From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	-5.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1799
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.61
	Confidence Interval	(2-Sided) 95%; -9.02 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Change in Alpha-2 Macroglobulin From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [mg/dL]	-9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3306
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.8
	Confidence Interval	(2-Sided) 95%; -21.2 to 7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Percent Change in Alpha-2 Macroglobulin From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	-4.85

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.4504
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.94
	Confidence Interval	(2-Sided) 95%; -7.25 to 3.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Change in Fibroblast Growth Factor 19 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Median (Full Range) [ng/L]	28.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1349
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	33.8
	Confidence Interval	(2-Sided) 95%; -11.5 to 79.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Percent Change in Fibroblast Growth Factor 19 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Median (Full Range) [percentage of change]	38.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0117
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	76.24
	Confidence Interval	(2-Sided) 95%; 19.04 to 133.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [ng/L]	24.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.4281
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	31.3
	Confidence Interval	(2-Sided) 95%; -50.3 to 112.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Percent Change in Fibroblast Growth Factor 19 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	42.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0407
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	117.37
	Confidence Interval	(2-Sided) 95%; 5.60 to 229.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Change in Fibroblast Growth Factor 21 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [ng/L]	2.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7065
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	47.28
	Confidence Interval	(2-Sided) 95%; -210.90 to 305.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Secondary Outcome

Title	Percent Change in Fibroblast Growth Factor 21 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	0.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1693
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	43.11
	Confidence Interval	(2-Sided) 95%; -19.95 to 106.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [ng/L]	-102.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7099
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-48.14
	Confidence Interval	(2-Sided) 95%; -317.64 to 221.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	Percent Change in Fibroblast Growth Factor 21 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	-15.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3597
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	30.03
	Confidence Interval	(2-Sided) 95%; -37.48 to 97.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

36. Secondary Outcome

Title	Change in Human Chitinase 3-like 1 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [ng/L]	5423.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.9893
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	169.0
	Confidence Interval	(2-Sided) 95%; -25908.2 to 26246.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Secondary Outcome

Title	Percent Change in Human Chitinase 3-like 1 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	8.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1454
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	13.82
	Confidence Interval	(2-Sided) 95%; -5.21 to 32.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

38. Secondary Outcome

Title	Change in Human Chitinase 3-like 1 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [ng/L]	5338.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.8089
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3016.8
	Confidence Interval	(2-Sided) 95%; -22996.2 to 29029.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Percent Change in Human Chitinase 3-like 1 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	8.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1365
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	12.78
	Confidence Interval	(2-Sided) 95%; -4.50 to 30.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Change in Hyaluronic Acid From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [µg/L]	6.210

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1322
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	28.954
	Confidence Interval	(2-Sided) 95%; -9.525 to 67.433
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Secondary Outcome

Title	Percent Change in Hyaluronic Acid From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	10.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1062
	Comments
	Method	t-test, 2 sided
	Comments	p-value for testing mean = 0
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	23.99
	Confidence Interval	(2-Sided) 95%; -5.59 to 53.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

42. Secondary Outcome

Title	Change in Hyaluronic Acid From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [µg/L]	6.100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0831
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	28.311
	Confidence Interval	(2-Sided) 95%; -4.151 to 60.774
	Parameter Dispersion	Type: Value:
	Estimation Comments

43. Secondary Outcome

Title	Percent Change in Hyaluronic Acid From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	6.99

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0543
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	32.72
	Confidence Interval	(2-Sided) 95%; -0.69 to 66.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

44. Secondary Outcome

Title	Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [score]	-0.160

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.6325
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.056
	Confidence Interval	(2-Sided) 95%; -0.185 to 0.298
	Parameter Dispersion	Type: Value:
	Estimation Comments

45. Secondary Outcome

Title	Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to Week 12
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	-1.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.6925
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; -1.94 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

46. Secondary Outcome

Title	Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	16
Median (Full Range) [score]	0.090

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.2733
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.161
	Confidence Interval	(2-Sided) 95%; -0.140 to 0.462
	Parameter Dispersion	Type: Value:
	Estimation Comments

47. Secondary Outcome

Title	Percent Change in Liver Fibrosis Score Enhanced Liver Fibrosis (ELF) From Baseline to End of Treatment
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	16
Median (Full Range) [percentage of change]	0.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3288
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95%; -1.63 to 4.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

48. Secondary Outcome

Title	Change in M30 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Median (Full Range) [U/L]	0.000

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.9271
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.649
	Confidence Interval	(2-Sided) 95%; -121.923 to 133.220
	Parameter Dispersion	Type: Value:
	Estimation Comments

49. Secondary Outcome

Title	Percent Change in M30 Biomarker From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Median (Full Range) [percentage of change]	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.9244
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; -18.58 to 20.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

50. Secondary Outcome

Title	Change in M30 Biomarker From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [U/L]	-34.920

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7288
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-30.244
	Confidence Interval	(2-Sided) 95%; -211.930 to 151.441
	Parameter Dispersion	Type: Value:
	Estimation Comments

51. Secondary Outcome

Title	Percent Change in M30 Biomarker From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	-5.48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7824
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.34
	Confidence Interval	(2-Sided) 95%; -21.85 to 28.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

52. Secondary Outcome

Title	Change in M65 Biomarker From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Median (Full Range) [U/L]	-15.605

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.6448
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-47.629
	Confidence Interval	(2-Sided) 95%; -260.433 to 165.176
	Parameter Dispersion	Type: Value:
	Estimation Comments

53. Secondary Outcome

Title	Percent Change in M65 Biomarker From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Median (Full Range) [percentage of change]	-3.52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.9806
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -32.04 to 32.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

54. Secondary Outcome

Title	Change in M65 Biomarker From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [U/L]	-58.970

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3256
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-113.616
	Confidence Interval	(2-Sided) 95%; -351.124 to 123.891
	Parameter Dispersion	Type: Value:
	Estimation Comments

55. Secondary Outcome

Title	Percent Change in M65 Biomarker From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	-11.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.6582
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.78
	Confidence Interval	(2-Sided) 95%; -32.52 to 50.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

56. Secondary Outcome

Title	Change in miR34a Fold From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	16
Median (Full Range) [fold change]	-0.0991

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.5459
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2438
	Confidence Interval	(2-Sided) 95%; -1.0847 to 0.5972
	Parameter Dispersion	Type: Value:
	Estimation Comments

57. Secondary Outcome

Title	Percent Change in miR34a Fold From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	16
Median (Full Range) [percentage of change]	-7.42

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.2860
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	23.91
	Confidence Interval	(2-Sided) 95%; -22.15 to 69.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

58. Secondary Outcome

Title	Change in miR34a Fold From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	16
Median (Full Range) [fold change]	-0.5019

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.4887
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2893
	Confidence Interval	(2-Sided) 95%; -1.1580 to 0.5794
	Parameter Dispersion	Type: Value:
	Estimation Comments

59. Secondary Outcome

Title	Percent Change in miR34a Fold From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	16
Median (Full Range) [percentage of change]	-24.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3610
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	30.27
	Confidence Interval	(2-Sided) 95%; -38.21 to 98.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

60. Secondary Outcome

Title	Change in Pro-C3 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [µg/L]	-0.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.4945
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -2.51 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

61. Secondary Outcome

Title	Percent Change in Pro-C3 From Baseline to Week 12
Description	The Full Analysis Set consisted of all patients who met the eligibility criteria and enrolled into the study (Visit 1 Day 1).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	-2.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.8191
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) 95%; -9.94 to 7.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

62. Secondary Outcome

Title	Change in Pro-C3 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [µg/L]	-2.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0243
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.22
	Confidence Interval	(2-Sided) 95%; -5.96 to -0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

63. Secondary Outcome

Title	Percent Change in Pro-C3 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	-12.70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0493
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-9.94
	Confidence Interval	(2-Sided) 95%; -19.84 to -0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

64. Secondary Outcome

Title	Change in Pro-C6 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [µg/L]	0.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3066
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; -0.59 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

65. Secondary Outcome

Title	Percent Change in Pro-C6 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	1.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.2671
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.40
	Confidence Interval	(2-Sided) 95%; -2.82 to 9.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

66. Secondary Outcome

Title	Change in Pro-C6 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [µg/L]	-0.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.8241
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.94 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

67. Secondary Outcome

Title	Percent Change in Pro-C6 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	-0.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.7587
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; -6.37 to 8.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

68. Secondary Outcome

Title	Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [µg/L]	-1.560

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3784
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.567
	Confidence Interval	(2-Sided) 95%; -1.880 to 0.746
	Parameter Dispersion	Type: Value:
	Estimation Comments

69. Secondary Outcome

Title	Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	-9.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3526
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.64
	Confidence Interval	(2-Sided) 95%; -14.80 to 5.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

70. Secondary Outcome

Title	Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [µg/L]	0.180

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.9218
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.098
	Confidence Interval	(2-Sided) 95%; -1.978 to 2.173
	Parameter Dispersion	Type: Value:
	Estimation Comments

71. Secondary Outcome

Title	Percent Change in Procollagen 3 N-terminal Pro-peptide From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	1.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.9833
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 95%; -14.71 to 15.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

72. Secondary Outcome

Title	Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [µg/L]	10.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3957
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	12.68
	Confidence Interval	(2-Sided) 95%; -17.79 to 43.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

73. Secondary Outcome

Title	Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to Week 12
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	21
Median (Full Range) [percentage of change]	3.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3440
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.81
	Confidence Interval	(2-Sided) 95%; -4.39 to 12.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

74. Secondary Outcome

Title	Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [µg/L]	13.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0607
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	15.22
	Confidence Interval	(2-Sided) 95%; -0.77 to 31.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

75. Secondary Outcome

Title	Percent Change in Tissue Inhibitor of Metalloproteinase 1 From Baseline to End of Treatment
Description	Non-invasive Fibrosis Biomarkers were assessed in blood samples.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	17
Median (Full Range) [percentage of change]	3.78

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0644
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.83
	Confidence Interval	(2-Sided) 95%; -0.39 to 12.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

76. Secondary Outcome

Title	Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Mean (Standard Deviation) [score]	-0.3665 (0.77812)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.0487
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.3665
	Confidence Interval	(2-Sided) 95%; -0.7306 to -0.0023
	Parameter Dispersion	Type: Value:
	Estimation Comments

77. Secondary Outcome

Title	Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to Week 12
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Mean (Standard Deviation) [percentage of change]	16.64 (136.529)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.5919
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	16.64
	Confidence Interval	(2-Sided) 95%; -47.25 to 80.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

78. Secondary Outcome

Title	Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	8
Mean (Standard Deviation) [score]	-0.2679 (0.43795)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1272
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2679
	Confidence Interval	(2-Sided) 95%; -0.6340 to 0.0983
	Parameter Dispersion	Type: Value:
	Estimation Comments

79. Secondary Outcome

Title	Percent Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score From Baseline to End of Treatment
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	8
Mean (Standard Deviation) [percentage of change]	15.02 (74.847)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.5881
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	15.02
	Confidence Interval	(2-Sided) 95%; -47.55 to 77.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

80. Secondary Outcome

Title	Change in Fibrosis-4 Score From Baseline to Week 12
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Mean (Standard Deviation) [score]	-0.18 (0.516)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1458
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.42 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

81. Secondary Outcome

Title	Percent Change in Fibrosis-4 Score From Baseline to Week 12
Description	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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	20
Mean (Standard Deviation) [percentage of change]	-11.53 (34.342)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.1495
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-11.53
	Confidence Interval	(2-Sided) 95%; -27.61 to 4.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

82. Secondary Outcome

Title	Change in Fibrosis-4 Score From Baseline to End of Treatment
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	8
Mean (Standard Deviation) [score]	-0.12 (0.328)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.3174
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

83. Secondary Outcome

Title	Percent Change in Fibrosis-4 Score From Baseline to End of Treatment
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
Measure Participants	8
Mean (Standard Deviation) [percentage of change]	-8.02 (17.754)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NTZ 500 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	Student's T-test was used for statistical inference.
Statistical Test of Hypothesis	p-Value	0.2420
	Comments	p-value for testing mean = 0
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.02
	Confidence Interval	(2-Sided) 95%; -22.86 to 6.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	from the signature of the informed consent form (ICF) until the end of study, week 28, i.e. 4 weeks after the last administration.
Adverse Event Reporting Description	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.
Arm/Group Title	NTZ 500 mg BID
Arm/Group Description	Open label group: all patients were to receive study drug Nitazoxanide 500mg BID for 24 weeks.
All Cause Mortality
	NTZ 500 mg BID
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	NTZ 500 mg BID
	Affected / at Risk (%)	# Events
Total	4/21 (19%)
Cardiac disorders
Atrial Fibrillation	1/21 (4.8%)	1
Angina Unstable	1/21 (4.8%)	1
Coronary Artery Disease	1/21 (4.8%)	1
cardiac failure	1/21 (4.8%)	1
Musculoskeletal and connective tissue disorders
Lumbar Spinal Stenosis	1/21 (4.8%)	1
Renal and urinary disorders
Nephrolithiasis	1/21 (4.8%)	1
Reproductive system and breast disorders
Menometrorrhagia	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	NTZ 500 mg BID
	Affected / at Risk (%)	# Events
Total	20/21 (95.2%)
Blood and lymphatic system disorders
Anaemia	2/21 (9.5%)
Splenomegaly	1/21 (4.8%)
Eye disorders
Vision blurred	1/21 (4.8%)
Gastrointestinal disorders
Diarrhoea	5/21 (23.8%)
Abdominal pain	3/21 (14.3%)
Nausea	3/21 (14.3%)
Abdominal pain upper	2/21 (9.5%)
Constipation	2/21 (9.5%)
Gastric ulcer	2/21 (9.5%)
Abdominal discomfort	1/21 (4.8%)
Abdominal distension	1/21 (4.8%)
Anorectal discomfort	1/21 (4.8%)
Dyspepsia	1/21 (4.8%)
Gastrointestinal pain	1/21 (4.8%)
Large intestine polyp	1/21 (4.8%)
Pancreatic cyst	1/21 (4.8%)
Toothache	1/21 (4.8%)
General disorders
Pain	2/21 (9.5%)
Fatigue	1/21 (4.8%)
Hepatobiliary disorders
Cholelithiasis	1/21 (4.8%)
Hepatic cirrhosis	1/21 (4.8%)
Portal hypertension	1/21 (4.8%)
Immune system disorders
Seasonal allergy	1/21 (4.8%)
Infections and infestations
Urinary tract infection	5/21 (23.8%)
Gastroenteritis viral	2/21 (9.5%)
Bronchitis	1/21 (4.8%)
Fungal skin infection	1/21 (4.8%)
Influenza	1/21 (4.8%)
Nasopharyngitis	1/21 (4.8%)
Tinea pedis	1/21 (4.8%)
Injury, poisoning and procedural complications
fall	3/21 (14.3%)
Arthropod sting	1/21 (4.8%)
Procedural pain	1/21 (4.8%)
Investigations
Blood cholesterol increased	1/21 (4.8%)
Blood creatine phosphokinase increased	1/21 (4.8%)
Blood creatinine increased	1/21 (4.8%)
Blood glucose increased	1/21 (4.8%)
Glomerular filtration rate increased	1/21 (4.8%)
Glycosylated haemoglobin increased	1/21 (4.8%)
Heart rate increased	1/21 (4.8%)
Norovirus test positive	1/21 (4.8%)
Weight increased	1/21 (4.8%)
Metabolism and nutrition disorders
Decreased appetite	2/21 (9.5%)
Diabetes mellitus	2/21 (9.5%)
Hypertryglyceridaemia	1/21 (4.8%)
Type 2 diabetes mellitus	1/21 (4.8%)
Musculoskeletal and connective tissue disorders
Muscle spasm	2/21 (9.5%)
Arthralgia	1/21 (4.8%)
Back pain	1/21 (4.8%)
Joint effusion	1/21 (4.8%)
Myalgia	1/21 (4.8%)
Nervous system disorders
Headache	2/21 (9.5%)
Dizziness	1/21 (4.8%)
Hepatic encephalopathy	1/21 (4.8%)
Hypoaesthesia	1/21 (4.8%)
Psychiatric disorders
Anxiety	1/21 (4.8%)
Renal and urinary disorders
Chromaturia	7/21 (33.3%)
Ureterolithiasis	1/21 (4.8%)
Reproductive system and breast disorders
Ovarian cyst	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/21 (4.8%)
Oropharyngeal pain	1/21 (4.8%)
Skin and subcutaneous tissue disorders
Pruritus	2/21 (9.5%)
Alopecia	1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.