A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)

• Sponsor: HighTide Biopharma Pty Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03656744
• Collaborator: (none)
• Enrollment: 101
• Locations: 17
• Arms: 3
• Actual Duration (Months): 15.4
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.

Condition or Disease	Intervention/Treatment	Phase
Fatty Liver, Nonalcoholic; NAFLD; Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis; Digestive System Diseases; Type 2 Diabetes Mellitus (T2DM)	Drug: HTD1801; Drug: Placebo	Phase 2

Detailed Description

This 18-week randomized, double-blind, parallel-group, proof of concept (POC), dose-ranging study compared multiple doses of HTD1801 to placebo in a 1:1:1 ratio. Since accumulation of hepatic fat is considered the "first hit" in the pathogenesis of NASH (Adams and Angulo 2006), change in liver fat content (LFC) by magnetic resonance imaging estimated proton density fat fraction (MRI-PDFF) is an appropriate primary endpoint and is consistent with that used in other recent Phase 2 POC studies in NASH (Harrison et al., 2018, Madrigal Pharmaceuticals 2018).

The Harrison et al., 2018, Madrigal Pharmaceuticals 2018 study showed clinically meaningful absolute and relative reductions in LFC assessed by MRI-PDFF over 12-week treatment periods thus, it was considered that an 18 week HTD1801 treatment period would therefore be adequate to assess the study's primary endpoint and to maximize collection of exposure and safety related data.

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM
• Actual Study Start Date: Nov 26, 2018
• Actual Primary Completion Date: Feb 7, 2020
• Actual Study Completion Date: Mar 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 500mg HTD1801, bid	Drug: HTD1801; HTD1801 tablets, 250mg
Experimental: 1000mg HTD1801, bid	Drug: HTD1801; HTD1801 tablets, 250mg
Placebo Comparator: placebo, bid	Drug: Placebo; tablets manufactured to mimic HTD1801 tablets

Outcome Measures

Primary Outcome Measures

1. Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF [Baseline through study Week 18]

   The primary endpoint was the absolute change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

Secondary Outcome Measures

1. Change in Fasting Glucose [Baseline through study Week 18]

   Change in fasting glucose from Baseline to Week 18 .

2. Changes in Hemoglobin A1c [Baseline through study week 18]

   Changes in HbA1c from Baseline to Week 18.

3. Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF [Baseline through study week 18]

   Proportion of subjects who achieved ≥ 30% relative reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

4. Relative Change in LFC as Measured by MRI-PDFF [Baseline through study week 18]

   Relative change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

5. Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF [Baseline through study Week 18]

   Number of subjects who normalized liver fat content (LFC) to <5% as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) at Week 18.

6. Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF [Baseline through study Week 18]

   Number of subjects who achieved ≥5% absolute reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

7. Change in HOMA-IR [Baseline through study week 18]

   Change in homeostasis model assessment-estimated insulin resistance (HOMA-IR) from Baseline to Week 18. The higher the HOMA-IR score, the more insulin resistant a person is. Values of <1 are considered optimal while values >2.9 indicate significant insulin resistance.

8. Change in LDL-c [Baseline visit through study week 18]

   Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.

9. Change in Serum Triglycerides [Baseline through study week 18]

   Change in serum triglycerides from Baseline to Week 18.

10. Change in HDL-c [Baseline through study week 18]

    Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.

11. Change in AST [Baseline through study week 18]

    Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.

12. Change in ALT [Baseline through study week 18]

    Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.

13. Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18 [Baseline through study week 18]

    Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.

14. Change in Pro-Peptide of Type III Collagen (Pro-C3) [Baseline through study week 18]

    Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.

15. Change in ELF Score [Baseline through study week 18]

    Change in the enhanced liver fibrosis (ELF) score. The ELF score is calculated using a published algorithm combining the values of a set of extracellular matrix markers, including TIMP-1, PIIINP, and HA. The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. The ELF score is hence used as a prognostic marker for disease progression: ELF score < 9.8 : Low risk of progression, ELF score 9.8 to < 11.3 : Moderate risk of progression and ELF score > = 11.3 : High risk of progression.

16. Change in TIMP-1 [Baseline through study week 18]

    Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.

17. Change in PIIINP [Baseline through study week 18]

    Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.

18. Change in HA [Baseline through study week 18]

    Change in hyaluronic acid (HA) from Baseline to Week 18.

19. Change in Total Bile Acids [Baseline through study week 18]

    Changes in total bile acids from Baseline to Week 18.

20. Change in FGF19 [Baseline through study week 18]

    Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18

21. Number of Participants Reporting an Adverse Events From Baseline Through Week 18 [Adverse events were collected from the time the subject signed the informed consent form through the date of the last visit for a specific subject, that is, approximately 24 weeks in total for a completed subject.]

    AEs were mapped to MedDRA version 20.1 preferred term (PT) and system organ class (SOC). If the subject experienced multiple events that mapped to a single preferred term, the greatest severity grade according to CTCAE Version 4.0, and strongest investigator assessment of relation to study medication was assigned to the preferred term. If an event had a missing severity or relationship, it was classified as having the highest severity and/or strongest relationship to study medication. The occurrence of TEAEs was summarized by treatment group by SOC, PT, and severity. Separate summaries of treatment-emergent serious adverse events (SAEs), TEAEs related to study drug, severe or life threatening TEAEs, and TEAEs leading to the discontinuation of study treatment were generated. Additionally, the occurrence of liver-specific AEs was summarized by treatment group. All reported adverse events were listed for individual subjects showing verbatim term, PT and SOC.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinical diagnosis of NASH as assessed by MRI

• Clinically documented diagnosis of T2DM

• Body mass index (BMI) >25 kg/m2

Exclusion Criteria:

• Liver disease unrelated to NASH

• Poorly controlled T2DM or Type 1 Diabetes Mellitus

• History of alcohol or substance abuse or dependence

• Inability to undergo MRI for any reason

• History of significant cardiovascular disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute for Liver Health	Chandler	Arizona	United States	85224
2	Institute for Liver Health	Tucson	Arizona	United States	85711
3	Adobe Clinical Research	Tucson	Arizona	United States	85712
4	National Research Institute	Panorama City	California	United States	91402
5	Excel Medical Clinical Trials	Boca Raton	Florida	United States	33434
6	Florida Research Institute	Lakewood Ranch	Florida	United States	34211
7	Compass Research	Orlando	Florida	United States	32806
8	Kansas City Research Institute	Kansas City	Missouri	United States	64131
9	Cumberland Research Associates	Fayetteville	North Carolina	United States	28304
10	Gastro One	Germantown	Tennessee	United States	38138
11	Digestive Health Research	Hermitage	Tennessee	United States	37076
12	Pinnacle Clinical Research	Austin	Texas	United States	78746
13	Doctors Hospital at Renaissance	Edinburg	Texas	United States	78539
14	Pinnacle Clinical Research	San Antonio	Texas	United States	78229
15	Texas Digestive Disease Consultants	Southlake	Texas	United States	76092
16	Harborview Medical Center	Seattle	Washington	United States	98195
17	University of Washington Medical Center	Seattle	Washington	United States	98195

Sponsors and Collaborators

• HighTide Biopharma Pty Ltd

Investigators

• Study Director: Adrian Di Bisceglie, MD,FACP,FAASLD, HighTide Therapeutics USA, LLC

Study Documents (Full-Text)

• Study Protocol - Mar 27, 2019
• Statistical Analysis Plan - Mar 25, 2020

More Information

Publications

None provided.

• Responsible Party: HighTide Biopharma Pty Ltd
• ClinicalTrials.gov Identifier: NCT03656744
• Other Study ID Numbers: HTD1801.PCT012
• First Posted: Sep 4, 2018
• Last Update Posted: Dec 29, 2021
• Last Verified: Nov 1, 2021

• 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: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Gastrointestinal Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Period Title: Overall Study
STARTED	34	34	33
COMPLETED	29	27	32
NOT COMPLETED	5	7	1

Baseline Characteristics

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid	Total
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets	Total of all reporting groups
Overall Participants	33	34	33	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (10.2)	53 (12.2)	58 (10.7)	56 (11.2)
Sex: Female, Male (Count of Participants)
Female	26 78.8%	24 70.6%	22 66.7%	72 72%
Male	7 21.2%	10 29.4%	11 33.3%	28 28%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 3%	1 2.9%	0 0%	2 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 9.1%	2 5.9%	0 0%	5 5%
White	29 87.9%	31 91.2%	31 93.9%	91 91%
More than one race	0 0%	0 0%	2 6.1%	2 2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
All Randomized Subjects (Count of Participants)
Disposition	33 100%	34 100%	33 100%	100 100%
Eligible Subjects	32 97%	33 97.1%	33 100%	98 98%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF
Description	The primary endpoint was the absolute change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.
Time Frame	Baseline through study Week 18

Outcome Measure Data

Analysis Population Description

Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	30	27	32
Mean (Standard Deviation) [Change in percentage of liver fat]	-2.918 (4.0204)	-4.829 (4.3516)	-1.962 (4.8844)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.199
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Change in Fasting Glucose
Description	Change in fasting glucose from Baseline to Week 18 .
Time Frame	Baseline through study Week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in glucose endpoint.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [mg/dL]	120 (28.6)	129 (42.5)	131 (40.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.152
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Changes in Hemoglobin A1c
Description	Changes in HbA1c from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for change in hemoglobin A1c endpoint..

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [Percentage]	-0.3 (0.68)	-0.6 (0.96)	0.1 (0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF
Description	Proportion of subjects who achieved ≥ 30% relative reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	30	27	32
Count of Participants [Participants]	6 18.2%	10 29.4%	7 21.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.884
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.236
	Comments
	Method	Regression, Logistic
	Comments

5. Secondary Outcome

Title	Relative Change in LFC as Measured by MRI-PDFF
Description	Relative change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	30	27	32
Mean (Standard Deviation) [Percentage change]	-15.097 (22.7749)	-24.140 (21.7020)	-8.322 (24.4804)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.196
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF
Description	Number of subjects who normalized liver fat content (LFC) to <5% as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) at Week 18.
Time Frame	Baseline through study Week 18

Outcome Measure Data

Analysis Population Description

Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	30	27	32
Count of Participants [Participants]	1 3%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.294
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

7. Secondary Outcome

Title	Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF
Description	Number of subjects who achieved ≥5% absolute reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.
Time Frame	Baseline through study Week 18

Outcome Measure Data

Analysis Population Description

Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	30	27	32
Count of Participants [Participants]	10 30.3%	12 35.3%	8 24.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.287
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.090
	Comments
	Method	Regression, Logistic
	Comments

8. Secondary Outcome

Title	Change in HOMA-IR
Description	Change in homeostasis model assessment-estimated insulin resistance (HOMA-IR) from Baseline to Week 18. The higher the HOMA-IR score, the more insulin resistant a person is. Values of <1 are considered optimal while values >2.9 indicate significant insulin resistance.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the changes in HOMA-IR endpoint and included 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [score on a scale]	-3.38 (6.779)	-4.21 (7.074)	-6.66 (17.752)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.201
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.534
	Comments
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Change in LDL-c
Description	Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.
Time Frame	Baseline visit through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the changes in LDL-c endpoint and included 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	27	25	29
Mean (Standard Deviation) [mg/dL]	5 (34.1)	-16 (26.5)	0 (20.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.955
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Change in Serum Triglycerides
Description	Change in serum triglycerides from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited subjects with data was available for the changes in serum triglycerides endpoint and included 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [mg/dL]	-41 (136.3)	-24 (70.4)	18 (142.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.120
	Comments
	Method	ANCOVA
	Comments

11. Secondary Outcome

Title	Change in HDL-c
Description	Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the change in HDL-c endpoint and included 4 more subjects than were in the Efficacy set..

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [mg/dL]	1 (5.7)	0 (8.2)	0 (7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.955
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	ANCOVA
	Comments

12. Secondary Outcome

Title	Change in AST
Description	Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures included subjects with data was available for the change in AST endpoint and included 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [U/L]	0 (13.2)	-13 (26.3)	-3 (11.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.488
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	ANCOVA
	Comments

13. Secondary Outcome

Title	Change in ALT
Description	Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the absolute change in alanine aminotransferase endpoint and had 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [U/L]	-4 (17.9)	-19 (27.2)	-3 (19.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.674
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	ANCOVA
	Comments

14. Secondary Outcome

Title	Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18
Description	Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

Subjects with elevated alanine aminotransferase (ALT) at Baseline

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	14	18	20
Count of Participants [Participants]	3 9.1%	9 26.5%	5 15.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.588
	Comments
	Method	Regression, Logistic
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.103
	Comments
	Method	Regression, Logistic
	Comments

15. Secondary Outcome

Title	Change in Pro-Peptide of Type III Collagen (Pro-C3)
Description	Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the change in Pro-C3 endpoint and included 4 more subjects than were in the Efficacy set...

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [ng/mL]	0.5 (5.17)	-2.3 (7.09)	-0.8 (2.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.236
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.944
	Comments
	Method	ANCOVA
	Comments

16. Secondary Outcome

Title	Change in ELF Score
Description	Change in the enhanced liver fibrosis (ELF) score. The ELF score is calculated using a published algorithm combining the values of a set of extracellular matrix markers, including TIMP-1, PIIINP, and HA. The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. The ELF score is hence used as a prognostic marker for disease progression: ELF score < 9.8 : Low risk of progression, ELF score 9.8 to < 11.3 : Moderate risk of progression and ELF score > = 11.3 : High risk of progression.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in ELF score endpoint and include 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	25	32
Mean (Standard Deviation) [score on a scale]	0.05 (0.723)	-0.10 (0.592)	-0.05 (0.461)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.267
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.911
	Comments
	Method	ANCOVA
	Comments

17. Secondary Outcome

Title	Change in TIMP-1
Description	Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in TIMP-1 endpoint and include 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	26	32
Mean (Standard Deviation) [µg/L]	1.8 (53.26)	-8.9 (57.32)	-6.0 (31.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.387
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.855
	Comments
	Method	ANCOVA
	Comments

18. Secondary Outcome

Title	Change in PIIINP
Description	Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in PIIINP and included 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	25	32
Mean (Standard Deviation) [µg/L]	0.68 (2.905)	0.03 (3.360)	-0.31 (2.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.489
	Comments
	Method	ANCOVA
	Comments

19. Secondary Outcome

Title	Change in HA
Description	Change in hyaluronic acid (HA) from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in HA and included set had 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	29	25	32
Mean (Standard Deviation) [µg/L]	-0.64 (35.398)	-5.25 (34.046)	-3.83 (49.844)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.515
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.887
	Comments
	Method	ANCOVA
	Comments

20. Secondary Outcome

Title	Change in Total Bile Acids
Description	Changes in total bile acids from Baseline to Week 18.
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in total bile acids and included for 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	11	12	13
Mean (Standard Deviation) [μmol/L]	1307 (1432.6)	1625 (2332.2)	-581 (1487.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	ANCOVA
	Comments

21. Secondary Outcome

Title	Change in FGF19
Description	Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18
Time Frame	Baseline through study week 18

Outcome Measure Data

Analysis Population Description

The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in FGF-19 and include 4 more subjects than were in the Efficacy set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	11	12	13
Mean (Standard Deviation) [μmol/L]	-11 (111.8)	-9 (71.1)	-40 (84.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.124
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1000mg HTD1801, Bid, Placebo, Bid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.171
	Comments
	Method	ANCOVA
	Comments

22. Secondary Outcome

Title	Number of Participants Reporting an Adverse Events From Baseline Through Week 18
Description	AEs were mapped to MedDRA version 20.1 preferred term (PT) and system organ class (SOC). If the subject experienced multiple events that mapped to a single preferred term, the greatest severity grade according to CTCAE Version 4.0, and strongest investigator assessment of relation to study medication was assigned to the preferred term. If an event had a missing severity or relationship, it was classified as having the highest severity and/or strongest relationship to study medication. The occurrence of TEAEs was summarized by treatment group by SOC, PT, and severity. Separate summaries of treatment-emergent serious adverse events (SAEs), TEAEs related to study drug, severe or life threatening TEAEs, and TEAEs leading to the discontinuation of study treatment were generated. Additionally, the occurrence of liver-specific AEs was summarized by treatment group. All reported adverse events were listed for individual subjects showing verbatim term, PT and SOC.
Time Frame	Adverse events were collected from the time the subject signed the informed consent form through the date of the last visit for a specific subject, that is, approximately 24 weeks in total for a completed subject.

Outcome Measure Data

Analysis Population Description

All subjects included in the safety set.

Arm/Group Title	500mg HTD1801, Bid	1000mg HTD1801, Bid	Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg	HTD1801: HTD1801 tablets, 250mg	Placebo: tablets manufactured to mimic HTD1801 tablets
Measure Participants	33	34	33
Count of Participants [Participants]	21 63.6%	26 76.5%	20 60.6%

Adverse Events

Time Frame	Adverse events were collected from the time the subject signed the informed consent form through the date of the last visit for a specific subject, that is, approximately 24 weeks for a completed subject.
Arm/Group Title	500mg HTD1801, Bid		1000mg HTD1801, Bid		Placebo, Bid
Arm/Group Description	HTD1801: HTD1801 tablets, 250mg		HTD1801: HTD1801 tablets, 250mg		Placebo: tablets manufactured to mimic HTD1801 tablets
All Cause Mortality
	500mg HTD1801, Bid		1000mg HTD1801, Bid		Placebo, Bid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/34 (0%)		0/33 (0%)
Serious Adverse Events
	500mg HTD1801, Bid		1000mg HTD1801, Bid		Placebo, Bid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/33 (3%)		1/34 (2.9%)		1/33 (3%)
Cardiac disorders
Myocardial infarction	1/33 (3%)	1	1/34 (2.9%)	1	0/33 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/33 (0%)	0	0/34 (0%)	0	1/33 (3%)	1
Respiratory, thoracic and mediastinal disorders
Decreased oxygen saturation	0/33 (0%)	0	1/34 (2.9%)	1	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	500mg HTD1801, Bid		1000mg HTD1801, Bid		Placebo, Bid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/33 (63.6%)		26/34 (76.5%)		20/33 (60.6%)
Endocrine disorders
Endocrine Disorders	0/33 (0%)	0	2/34 (5.9%)	2	0/33 (0%)	0
Gastrointestinal disorders
Gastrointestinal Disorders	14/33 (42.4%)	27	19/34 (55.9%)	40	10/33 (30.3%)	19
General disorders
General Disorders	2/33 (6.1%)	5	3/34 (8.8%)	4	0/33 (0%)	0
Infections and infestations
Infections and Infestations	4/33 (12.1%)	4	5/34 (14.7%)	5	11/33 (33.3%)	18
Injury, poisoning and procedural complications
Injury	1/33 (3%)	1	0/34 (0%)	0	2/33 (6.1%)	2
Metabolism and nutrition disorders
Metabolic disorders	0/33 (0%)	0	2/34 (5.9%)	4	2/33 (6.1%)	3
Nervous system disorders
Nervous system disorders	3/33 (9.1%)	3	5/34 (14.7%)	6	3/33 (9.1%)	4
Respiratory, thoracic and mediastinal disorders
Respiratory disorders	1/33 (3%)	2	1/34 (2.9%)	2	3/33 (9.1%)	6
Skin and subcutaneous tissue disorders
Skin disorders	1/33 (3%)	2	2/34 (5.9%)	3	1/33 (3%)	1

Limitations/Caveats

The study was conducted exclusively in the United States and data may not be applicable to other populations. The study enrolled subjects with presumed NASH and diabetes. Further studies to determine the effect of HTD1801 in non-diabetics may be needed. Future studies will focus on patients with biopsy confirmed NASH and use liver histology (i.e., liver biopsies) as a histological endpoint.

More Information

Certain Agreements

Principal Investigators are NOT 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.