Study of Gemcabene in Adults With FPLD

• Sponsor: Elif Oral (Other)
• Overall Status: Completed
• CT.gov ID: NCT03508687
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The overall objective of this study is to assess the efficacy and safety of two dosing regimens of gemcabene (300 mg once daily for 24 weeks or 300 mg daily for 12 weeks followed by 600 mg daily for 12 weeks) in up to eight patients with Familial Partial Lipodystrophy with high triglycerides and Non-Alcoholic Fatty Liver Disease. The study will consist of a six week Wash Out Period, up to a 28 day Screening Period, a 24 week Treatment Period, and a follow-on safety assessment four weeks post final dose. Study participation will last approximately 4 months and includes at least 9 study visits, and can be as many as 11 study visits.

Condition or Disease	Intervention/Treatment	Phase
Familial Partial Lipodystrophy; Hypertriglyceridemia; Fatty Liver; NASH - Nonalcoholic Steatohepatitis	Drug: 300mg Gemcabene; Drug: 600mg Gemcabene	Phase 1/Phase 2

Detailed Description

Patients with typical Familial Partial Lipodystrophy Disease (FPLD) have a marked loss of subcutaneous fat from the extremities and trunk accompanied by a variable amount of excess fat deposition in the nonlipodystrophic areas such as the face, chin, back, and intraabdominal regions. Dietary fat restriction and other lifestyle changes are first line therapy to avoid weight gain, critical for effective management of metabolic complications in patients with lipodystrophy. However, despite lifestyle changes and conventional hypoglycemic and hypolipidemic therapies, some FPLD patients continue to have extreme hypertriglyceridemia, hepatic steatosis, and poorly controlled diabetes.Hypertriglyceridemia is a common condition of FPLD and serum triglyceride levels of 250-1999 mg/dL, classified as moderate to severe hypertriglyceridemia, indicate risk for development of very severe hypertriglyceridemia, causative of pancreatitis and hepatic steatosis. In patients such as those with FPLD with severe or very severe hypertriglyceridemia, fibrates, omega-3 fatty acids (OMG-3) and occasionally niacin are first-line therapy. Non-alcoholic fatty liver disease (NAFLD) is often associated with FPLD. The spectrum of NAFLD associated with FPLD which appears to be more frequent than what is seen in common Type 2 diabetes and appears more severe than common forms of NAFLD and very often associated with NASH. The etiology for the latter is not clear, however, the fact that a mouse model of liver specific laminopathy develops NASH in a cell -autonomous manner suggests that the specific cellular defects seen in FPLD may play a role in the development of NAFLD/NASH. Triglyceride content in the liver is regulated by fatty acid uptake as well as fatty acid and VLDL production rates. Derangements in these processes, such as excessive production of fatty acids and triglycerides that can occur with excessive carbohydrate consumption contribute to NAFLD. Patients with NAFLD compared to controls, present with an atherogenic dyslipidemic profile, characterized by increased serum levels of triglycerides, ApoB, VLDL-C, and LDL-C with a proportionally greater content of small dense LDL-C (sdLDL-C) 18-20. NAFLD is also associated with aberrant nuclear receptor function and systemic inflammation. NAFLD can progress to NASH. NASH is marked by hepatocyte ballooning and liver inflammation, which may progress to scarring and irreversible damage. Macro and microscopically, NASH is characterized by lobular and/or portal inflammation, varying degrees of fibrosis, hepatocyte death and pathological angiogenesis. At its most severe, NASH can progress to cirrhosis, hepatocellular carcinoma (HCC) and liver failure. It is estimated that 20-33% NAFLD patients will progress to NASH, with about 5% ultimately progressing to cirrhosis. Cirrhosis has a reported 7- to 10-year mortality of 12-25%. As NAFLD and NASH continue to be a growing epidemic, gemcabene's clinical and preclinical data suggest that this novel agent may provide benefit to patients with the diagnosis of NAFLD and/or NASH. As such, further development of gemcabene may help meet an unmet medical need in these patient populations. In Phase 2 studies, gemcabene has shown triglyceride lowering from 20 to > 50% based on dose and severity of hypertriglyceridemia and lowering in hsCRP of up to 50%. Additionally, in animal and cell based models, gemcabene studies have provided evidence demonstrating: reduction in de-novo lipogenesis, reduction in intrahepatic TG levels, modulation of inflammation and reduction of the NAFLD activity score, particularly related to hepatic ballooning, steatosis, fibrosis, and collagen accumulation. As such gemcabene may have utility in hypertriglyceridemia of FLP and ultimately in the prevention or treatment of NASH in these patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Investigator-Initiated Open-Label, Randomized Study of Gemcabene in Adults With Familial Partial Lipodystrophy Disease (FPLD)
• Actual Study Start Date: Mar 13, 2018
• Actual Primary Completion Date: Jul 31, 2019
• Actual Study Completion Date: Jul 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: 300 mg Gemcabene daily week 12-24 Patients took Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients were randomized 1:1 according to pre-generated randomization code. This arm received 300mg Gemcabene daily for 12 weeks total, starting at week 12.	Drug: 300mg Gemcabene; 300mg Gemcabene
Experimental: Group 2: 600mg Gemcabene daily week 12-24 Patients took Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients were randomized 1:1 according to pre-generated randomization code. This arm received 600mg Gemcabene daily for 12 weeks total, starting at week 12.	Drug: 600mg Gemcabene; 600mg Gemcabene

Outcome Measures

Primary Outcome Measures

1. Change in Fasting Serum Triglyceride (at 12 Weeks) [Baseline to week 12]

   This is measured by percent change in fasting serum triglyceride from baseline to week 12

Secondary Outcome Measures

1. Change in Fasting Serum Triglycerides (Through 24 Weeks) [Baseline, week 6 and week 12, week 24]

   This is measured by change in fasting serum triglyceride from baseline to average of weeks 6 and 12, and week 24 and change in fasting serum triglyceride from baseline to week 12

2. Percent Change in Fasting Serum Triglycerides (Through 24 Weeks) [Baseline, week 6 and week 12, week 24]

   This is measured by percent change in fasting serum triglyceride from baseline to average of weeks 6 and 12, and week 24 and change in fasting serum triglyceride from baseline to week 12

3. Change in Liver Fat Content as Measured by Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF) [Baseline, week 12, week 24]

   This is measured by change in liver fat content using Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF) from baseline to week 12 and week 24

4. Percent Change in Liver Fat Content as Measured by Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF) [Baseline, week 12, week 24]

   This is measured by percent change in liver fat content using Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF) from baseline to week 12 and week 24

5. Change in Liver Fibrosis [Baseline, Week 12, and Week 24]

   This is measured by change in liver fibrosis using MR-elastography from baseline to week 12 and week 24

6. Percent Change in Liver Fibrosis [Baseline, Week 12, and Week 24]

   This is measured by percent change in liver fibrosis using MR-elastography from baseline to week 12 and week 24

7. Change in NAS (Non-alcoholic Steatohepatitis) [Baseline to week 24]

   This is measured by change in NAS via non-alcoholic fatty liver disease activity score. NAS is the unweighted sum of steatosis, lobular inflammation and hepatocyte ballooning from baseline to week 24. Total NAS scores can range from 0 to 8. The higher the NAS score, the more severe the liver disease.

8. Percent Change in NAS (Non-alcoholic Steatohepatitis) [Baseline to week 24]

   This is measured by change in NAS via non-alcoholic fatty liver disease activity score. NAS is the unweighted sum of steatosis, lobular inflammation and hepatocyte ballooning from baseline to week 24. Total NAS scores can range from 0 to 8. The higher the NAS score, the more severe the liver disease.

9. Change in Cholesterol [Baseline, week 6 and week 12, week 24]

   This will be measured by change in total, HDL and LDL levels in mg/dL

10. Percent Change in Cholesterol [Baseline, week 6 and week 12, week 24]

    This will be measured as percent change in total, HDL and LDL levels in mg/dL.

11. Change in Apolipoprotein [Baseline, week 6 and week 12, week 24]

    This will be measured by change in apolipoprotein A and B in mg/dL

12. Percent Change in Apolipoprotein [Baseline, week 6 and week 12, week 24]

    This will be measured by percent change in apolipoprotein A and B in mg/dL

13. Change in High-Sensitivity C-Reactive Protein (hsCRP) [Baseline, week 12, week 24]

    This is measured by change in high-sensitivity C-reactive protein (hsCRP) from baseline to weeks 12 and week 24

14. Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) [Baseline, week 12, week 24]

    This is measured by percent change in high-sensitivity C-reactive protein (hsCRP) from baseline to weeks 12 and week 24

15. Change in Alanine Aminotransferase (ALT) [Baseline, week 12, week 24]

    This is measured by change in alanine aminotransferase (ALT) from baseline to weeks 12 and week 24

16. Percent Change in Alanine Aminotransferase (ALT) [Baseline, week 12, week 24]

    This is measured by percent change in alanine aminotransferase (ALT) from baseline to weeks 12 and week 24

17. Change in Aspartate Aminotransferase (AST) [Baseline, week 12, week 24]

    This is measured by change in aspartate aminotransferase (AST) from baseline to weeks 12 and week 24

18. Percent Change in Aspartate Aminotransferase (AST) [Baseline, week 12, week 24]

    This is measured by percent change in aspartate aminotransferase (AST) from baseline to weeks 12 and week 24

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• Clinical diagnosis of lipodystrophy based on a lack of body fat in a partial fashion assessed by physical examination, and at least 1 MAJOR criterion (below):

• Low skinfold thickness in anterior thigh by caliper measurement: men (≤ 10 mm) and women (≤ 22 mm) OR

• Historic genetic diagnosis of familial partial lipodystrophy (e.g. mutations in LMNA, PPAR-γ, AKT2, or PLIN1 genes) as supported by source documentation

• Hepatic steatosis (>10% - Stage 2 or 3) as demonstrated by MRI-PDFF;

• Alcohol intake of less than 20 g per day in females and 30 g per day in males (one 12 oz beer, one glass of wine, or 2 oz of spirits or liquor equals roughly 10 g of alcohol;

• Mean fasting triglyceride value ≥ 250 mg/dL at the Screening Visit;

• Background lipid lowering medications must be stable for at least 6 weeks prior to the Screening Visit;

• Women patients must not be pregnant or lactating and women of child-bearing potential must agree to use acceptable methods of contraception throughout the duration of the study and for 30 days after the last dose of study drug. Male patients must agree to use contraception by means of a condom and may not donate sperm throughout the duration of the study and for 8 days after the last dose of study drug.

• Weight greater than 50 kg (~110 lbs); with a body mass index (BMI) of no more than 45 kg/m²;

• Have not used a fibrate with in the last 6 weeks and/or thiazolidinediones (TZDs) within the last 12 weeks prior to the Screening visit.

• Do not have a hypersensitivity or a history of significant reactions of fibrates.

• Are not currently taking potent CYP3A4 inhibitors such as itraconazole or a macrolide antibiotic.

• Have a condition or finding which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48105

Sponsors and Collaborators

• Elif Oral

Investigators

• Principal Investigator: Elif A Oral, M.D., University of Michigan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 11, 2019

More Information

Publications

None provided.

• Responsible Party: Elif Oral, Professor of Medicine, University of Michigan
• ClinicalTrials.gov Identifier: NCT03508687
• Other Study ID Numbers: HUM00130803
• First Posted: Apr 26, 2018
• Last Update Posted: Aug 17, 2020
• Last Verified: Jul 1, 2020

• 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; Lipodystrophy, Familial Partial; Lipodystrophy; Hypertriglyceridemia

Study Results

Participant Flow

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Period Title: Overall Study
STARTED	2	3
COMPLETED	2	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24	Total
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene	Total of all reporting groups
Overall Participants	2	3	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	3 100%	5 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56	52	54
Sex: Female, Male (Count of Participants)
Female	2 100%	3 100%	5 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	3 100%	5 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Fasting Serum Triglycerides (mg/dL) [Mean (Full Range) ]
Mean (Full Range) [mg/dL]	283	790	587

Outcome Measures

1. Primary Outcome

Title	Change in Fasting Serum Triglyceride (at 12 Weeks)
Description	This is measured by percent change in fasting serum triglyceride from baseline to week 12
Time Frame	Baseline to week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Mean (Full Range) [percent change]	-0.44	-20.27

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: 300 mg Gemcabene Daily Week 1-24, Group 2: 600mg Gemcabene Daily Week 12-24
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.517
	Comments	paired t test; baseline vs. week 12 (n = 5)
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: 300 mg Gemcabene Daily Week 1-24, Group 2: 600mg Gemcabene Daily Week 12-24
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.345
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Wilcoxon Signed Ranks Test (n = 5)

2. Secondary Outcome

Title	Change in Fasting Serum Triglycerides (Through 24 Weeks)
Description	This is measured by change in fasting serum triglyceride from baseline to average of weeks 6 and 12, and week 24 and change in fasting serum triglyceride from baseline to week 12
Time Frame	Baseline, week 6 and week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Baseline to average of W6, W12, W24	9.25	-126.22
Baseline to W12	-10.75	-189.33

3. Secondary Outcome

Title	Percent Change in Fasting Serum Triglycerides (Through 24 Weeks)
Description	This is measured by percent change in fasting serum triglyceride from baseline to average of weeks 6 and 12, and week 24 and change in fasting serum triglyceride from baseline to week 12
Time Frame	Baseline, week 6 and week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 12-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Baseline to average of W6, W12, and W24	5.56	-18.91
Baseline to Week 12	-0.44	-19.91

4. Secondary Outcome

Title	Change in Liver Fat Content as Measured by Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF)
Description	This is measured by change in liver fat content using Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF) from baseline to week 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Baseline to Week 12	2.71	1.01
Baseline to Week 24	12.75	-1.27

5. Secondary Outcome

Title	Percent Change in Liver Fat Content as Measured by Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF)
Description	This is measured by percent change in liver fat content using Magnetic Resonance Imaging - Protein Density Fat Fraction (MRI-PDFF) from baseline to week 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Baseline to Week 12	25.66	11.57
Baseline to Week 24	104.88	-3.36

6. Secondary Outcome

Title	Change in Liver Fibrosis
Description	This is measured by change in liver fibrosis using MR-elastography from baseline to week 12 and week 24
Time Frame	Baseline, Week 12, and Week 24

Outcome Measure Data

Analysis Population Description

Percentage of change in Preliminary Hepatic Fat-Fraction (PDFF)

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Baseline to Week 12	-0.63	0.96
Baseline to Week 24	-0.03	.45

7. Secondary Outcome

Title	Percent Change in Liver Fibrosis
Description	This is measured by percent change in liver fibrosis using MR-elastography from baseline to week 12 and week 24
Time Frame	Baseline, Week 12, and Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Baseline to Week 12	-19.07	27.84
Baseline to Week 24	-0.37	41.55

8. Secondary Outcome

Title	Change in NAS (Non-alcoholic Steatohepatitis)
Description	This is measured by change in NAS via non-alcoholic fatty liver disease activity score. NAS is the unweighted sum of steatosis, lobular inflammation and hepatocyte ballooning from baseline to week 24. Total NAS scores can range from 0 to 8. The higher the NAS score, the more severe the liver disease.
Time Frame	Baseline to week 24

Outcome Measure Data

Analysis Population Description

Liver biopsy was performed in two participants at baseline (1 subject in group-1 and another subject in group-2). Paired liver biopsy was only available for the subject in group-1.

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	1	1
Mean (Full Range) [scores on a scale (NAFLD activity score)]	2	NA

9. Secondary Outcome

Title	Percent Change in NAS (Non-alcoholic Steatohepatitis)
Description	This is measured by change in NAS via non-alcoholic fatty liver disease activity score. NAS is the unweighted sum of steatosis, lobular inflammation and hepatocyte ballooning from baseline to week 24. Total NAS scores can range from 0 to 8. The higher the NAS score, the more severe the liver disease.
Time Frame	Baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	1	1
Mean (Full Range) [percent change]	100	NA

10. Secondary Outcome

Title	Change in Cholesterol
Description	This will be measured by change in total, HDL and LDL levels in mg/dL
Time Frame	Baseline, week 6 and week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Total Cholesterol Baseline to Week 12	-7.00	-16.67
Total Cholesterol Baseline to Week 24	20.50	23.67

11. Secondary Outcome

Title	Percent Change in Cholesterol
Description	This will be measured as percent change in total, HDL and LDL levels in mg/dL.
Time Frame	Baseline, week 6 and week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Total Cholesterol Baseline to Week 12	-4.08	-7.61
Total Cholesterol Baseline to Week 24	12.52	6.73

12. Secondary Outcome

Title	Change in Apolipoprotein
Description	This will be measured by change in apolipoprotein A and B in mg/dL
Time Frame	Baseline, week 6 and week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Apolipoprotein B Baseline to Week 12	-4.35	-8.76
Apolipoprotein B Baseline to Week 24	6.74	7.57

13. Secondary Outcome

Title	Percent Change in Apolipoprotein
Description	This will be measured by percent change in apolipoprotein A and B in mg/dL
Time Frame	Baseline, week 6 and week 12, week 24

Outcome Measure Data

Analysis Population Description

% Change in participants in group A and group B

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
Apolipoprotein B Baseline to Week 12	-5.38	-6.04
Apolipoprotein B Baseline to Week 24	8.60	5.02

14. Secondary Outcome

Title	Change in High-Sensitivity C-Reactive Protein (hsCRP)
Description	This is measured by change in high-sensitivity C-reactive protein (hsCRP) from baseline to weeks 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
hsCRP Baseline to Week 12	-0.70	-0.33
hsCRP Baseline to Week 24	0.15	0.77

15. Secondary Outcome

Title	Percent Change in High-Sensitivity C-Reactive Protein (hsCRP)
Description	This is measured by percent change in high-sensitivity C-reactive protein (hsCRP) from baseline to weeks 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
hsCRP Baseline to W12	-42.36	3.71
hsCRP Baseline to W24	15.28	43.41

16. Secondary Outcome

Title	Change in Alanine Aminotransferase (ALT)
Description	This is measured by change in alanine aminotransferase (ALT) from baseline to weeks 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
ALT Baseline to Week 12	2.50	13.33
ALT Baseline to Week 24	22.50	40.67

17. Secondary Outcome

Title	Percent Change in Alanine Aminotransferase (ALT)
Description	This is measured by percent change in alanine aminotransferase (ALT) from baseline to weeks 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
ALT Baseline to W12	6.32	40.10
ALT Baseline to W24	58.78	82.17

18. Secondary Outcome

Title	Change in Aspartate Aminotransferase (AST)
Description	This is measured by change in aspartate aminotransferase (AST) from baseline to weeks 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
AST Baseline to Week 12	6.00	8.00
AST Baseline to Week 24	11.00	62.67

19. Secondary Outcome

Title	Percent Change in Aspartate Aminotransferase (AST)
Description	This is measured by percent change in aspartate aminotransferase (AST) from baseline to weeks 12 and week 24
Time Frame	Baseline, week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24	Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
Measure Participants	2	3
AST Baseline to W12	19.25	25.44
AST Baseline to W24	35.56	160.41

Adverse Events

Time Frame	28 weeks (24 week Treatment Period, and a follow-on safety assessment 4 weeks post final dose)
Arm/Group Title	Group 1: 300 mg Gemcabene Daily Week 1-24		Group 2: 600mg Gemcabene Daily Week 12-24
Arm/Group Description	Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 300mg Gemcabene daily for 12 weeks total, starting at week 12. 300mg Gemcabene: 300mg Gemcabene		Patients will take Gemcabene 300mg daily for weeks 1-12. After 12 weeks, at visit T4, patients will be randomized 1:1 according to pre-generated randomization code to either of the following groups. Group 1: Gemcabene 300mg daily for weeks 12-24. Group 2: Gemcabene 600mg daily for weeks 12-24. This arm will receive 600mg Gemcabene daily for 12 weeks total, starting at week 12. 600mg Gemcabene: 600mg Gemcabene
All Cause Mortality
	Group 1: 300 mg Gemcabene Daily Week 1-24		Group 2: 600mg Gemcabene Daily Week 12-24
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)
Serious Adverse Events
	Group 1: 300 mg Gemcabene Daily Week 1-24		Group 2: 600mg Gemcabene Daily Week 12-24
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		1/3 (33.3%)
Nervous system disorders
Vertigo	0/2 (0%)		1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Group 1: 300 mg Gemcabene Daily Week 1-24		Group 2: 600mg Gemcabene Daily Week 12-24
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		3/3 (100%)
Cardiac disorders
Palpitations	1/2 (50%)	1	0/3 (0%)	0
Endocrine disorders
hypoglycemia	0/2 (0%)	0	1/3 (33.3%)	1
increase in calcium level (lab)	0/2 (0%)	0	1/3 (33.3%)	1
Increased Blood Sugars	0/2 (0%)	0	1/3 (33.3%)	1
Gastrointestinal disorders
Bloating	1/2 (50%)	1	0/3 (0%)	0
Abdominal Pain	0/2 (0%)	0	1/3 (33.3%)	1
GERD	0/2 (0%)	0	1/3 (33.3%)	1
Nausea	0/2 (0%)	0	1/3 (33.3%)	2
Stomach pain	0/2 (0%)	0	1/3 (33.3%)	1
vomited (intermittent)	0/2 (0%)	0	1/3 (33.3%)	1
General disorders
Fatigue	1/2 (50%)	1	0/3 (0%)	0
Body Pain	0/2 (0%)	0	1/3 (33.3%)	1
Increase in fatigue	0/2 (0%)	0	1/3 (33.3%)	1
Increased stress levels	0/2 (0%)	0	1/3 (33.3%)	1
upper right quadrant pain of abdomen	0/2 (0%)	0	1/3 (33.3%)	1
Hepatobiliary disorders
Increase in liver fat	2/2 (100%)	2	1/3 (33.3%)	1
Increased GGTP	0/2 (0%)	0	2/3 (66.7%)	2
increased liver enzymes	0/2 (0%)	0	2/3 (66.7%)	3
Immune system disorders
increased CRP	0/2 (0%)	0	1/3 (33.3%)	1
Infections and infestations
Upper Respiratory Infection	1/2 (50%)	1	1/3 (33.3%)	1
Cellulitis on R finger	1/2 (50%)	1	0/3 (0%)	0
Sore Throat	1/2 (50%)	1	0/3 (0%)	0
HSV Outbreak	0/2 (0%)	0	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Pain from Liver Bx	1/2 (50%)	1	0/3 (0%)	0
Fall down steps	0/2 (0%)	0	1/3 (33.3%)	1
Investigations
Lesion L side of mouth	0/2 (0%)	0	1/3 (33.3%)	1
Metabolism and nutrition disorders
Increased Hunger	1/2 (50%)	1	1/3 (33.3%)	1
weight loss	0/2 (0%)	0	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Increased Muscle Pain	1/2 (50%)	1	0/3 (0%)	0
Arthritis of thumb	1/2 (50%)	1	0/3 (0%)	0
Increase in Creatinine Phosphokinase	1/2 (50%)	1	0/3 (0%)	0
Back Pain	0/2 (0%)	0	1/3 (33.3%)	1
increased pain hips (arthritis)	0/2 (0%)	0	1/3 (33.3%)	1
Pain increased knees both (arthritis bath)	0/2 (0%)	0	1/3 (33.3%)	1
Shoulder soreness/stiffness	0/2 (0%)	0	1/3 (33.3%)	1
Nervous system disorders
dizzyness 'spell' has history of these last episode ago 1 year	0/2 (0%)	0	1/3 (33.3%)	1
Headache (migraine)	0/2 (0%)	0	1/3 (33.3%)	1
Increased diabetic neuropathy	0/2 (0%)	0	2/3 (66.7%)	2
Increased headaches	0/2 (0%)	0	1/3 (33.3%)	1
Psychiatric disorders
Depression	1/2 (50%)	1	0/3 (0%)	0
Renal and urinary disorders
Kidney Stones	1/2 (50%)	1	1/3 (33.3%)	1
Decreased EGFR non-black	0/2 (0%)	0	1/3 (33.3%)	1
Increased Creatinine	0/2 (0%)	0	2/3 (66.7%)	2
Skin and subcutaneous tissue disorders
Dry skin itchniness	0/2 (0%)	0	1/3 (33.3%)	1
Vascular disorders
Increased Hypertension	1/2 (50%)	1	0/3 (0%)	0

Limitations/Caveats

The expected number of study subjects (8), was not reached.

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.