Nonalcoholic Steatohapatitis
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the effect of roflumilast and pioglitazone therapy on serum transaminase (ALT) levels in adults with Nonalcoholic SteatoHepatitis.
Detailed description
This proof of concept study will evaluate the effect of roflumilast and pioglitazone on transaminase levels and liver fat content. Takeda has chosen not to continue this Study, however, randomized subjects were allowed to complete the study per protocol. The decision to terminate the study is not related to any safety concerns with either of the study medications.
Interventions
DRUGRoflumilast
Roflumilast dose
DRUGPioglitazone
Pioglitazone dose
DRUGPlacebo
Pioglitazone placebo-matching dose
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements. 2. The patient or, when applicable, the patient's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Has a historical diagnosis of NASH, established no more than 12 months prior to study entry based on histology (liver biopsy). 4. Has a NAFLD Activity Score (NAS) of ≥3, with a score of at least 1 in steatosis and lobular inflammation - the subcomponents of NAS. It is acceptable if the score for hepatocyte ballooning is zero. 5. The subject has a MRI determined liver fat fraction of equal or higher than 7 percent. 6. The subject is female or male and aged 18 to 80 years, inclusive. 7. A male who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 weeks after last dose. 8. A female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose. 9. If taking Vitamin E and/or pentoxifylline, the subject has been receiving a stable dose for 6 months prior to randomization, started Vitamin E and/or pentoxifylline therapy prior to the qualifying liver biopsy, and agrees to maintain a stable dose throughout the study when possible. 10. Subject has an ALT level at Screening between 55 and 250 IU/L, inclusive, and between 60 and 250 IU/L at one other occasion during the 6 months prior to Randomization. 11. If taking a statin, should be on stable dose for 6 months prior to screening. 12. If taking angiotensin receptor blockers and fish oil, should be on a stable dose for at least 3 month prior to screening. 13. If diabetic, the subject is on a stable dose of metformin, dipeptidyl peptidase-4 inhibitor, sulfonylurea or insulin or a combination thereof for at least 3 months prior to Screening.
Exclusion criteria
1. The subject has a history of chronic liver disease other than NASH eg, chronic or acute hepatitis, Wilson's disease, alcoholic liver diseases or any other non-NASH active liver disease. 2. Subjects with liver cirrhosis (of any cause) or laboratory or clinical signs of functional liver failure 3. Clinically relevant abnormal laboratory values suggesting an undiagnosed disease other than NASH requiring further clinical evaluation (as assessed by the Investigator). 4. The subject has active cancer or a history of a malignant disease (except basal cell carcinoma) within 5 years prior to Screening or any history of bladder cancer. 5. Subject with a history of weight loss or weight gain of \>10 pounds within 6 months prior to Screening. 6. Subject with a history of bariatric surgery within 5 years prior to Screening. 7. The subject has received any investigational compound within 30 days prior to Screening or is currently participating in another clinical study. 8. The subject has a history of hypersensitivity or allergies to roflumilast or pioglitazone including any associated excipients. 9. The subject is required to take excluded medications. 10. The subject has taken oral or injectable glucocorticoids for longer than 7 days within 3 months prior to Screening. 11. The subject has poorly controlled Type 1 or Type 2 diabetes mellitus with an HbA1c ≥8.5 at Screening or per Investigator judgment. 12. The subject has hepatitis A, B or C. 13. The subject has severe immunological diseases (eg, known HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy) assessed at Screening. 14. The subject had a history of diabetic gastroparesis or history of gastric bypass surgery. 15. The subject had a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening. 16. The subject had New York Heart Association heart failure of Class (II-IV) regardless of therapy. 17. The subject had a diastolic blood pressure greater than 100 mm Hg or a systolic blood pressure of greater than 160 mm Hg (The mean of the 3 serial BP measurements will be used to determine subject eligibility). 18. The subject has presence or history of psychotic disorder that may be associated with suicidal thinking, ideation or behavior. These disorders include, but are not limited to, depression, psychosis, psychotic disorder, and schizophrenia. Subjects will be monitored by Columbia-Suicide Severity Rating Scales throughout the duration of the study. 19. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day for women or 3 alcoholic drinks per day for men. One drink is equivalent to a 12-ounce beer, a 4-ounce glass of wine, or a 1-ounce shot of hard liquor.) within 1 year prior to the Screening visit. 20. The subject has a hemoglobin \<120 g/L for men and \<100 g/L for women. 21. The subject has received pioglitazone or roflumilast in a previous clinical study or as a therapeutic agent within 1 year prior to screening. 22. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. 23. The subject is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 24. The subject has significant results from physical examinations or clinical laboratory results that, at the discretion of the investigator, would make it difficult to successfully manage and follow the subject according to the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Serum Alanine Transaminase (ALT) at Baseline | Baseline | — |
| Percent Change From Baseline in Serum ALT at Month 4 | Month 4 | The percent change between the serum ALT value collected at Month 4 or final visit relative to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amount of Serum Aspartate Transaminase (AST) at Baseline | Baseline | — |
| Percent Change From Baseline in Serum AST at Month 4 | Month 4 | The percent change between the serum AST value collected at Month 4 or final visit relative to baseline. |
| Liver Fat Content at Baseline | Baseline | Liver fat content was quantitatively measured by evaluating the percentage of proton density fat fraction (PDFF) from an abdominal magnetic resonance imaging (MRI). On the basis of Couinaud classification (a classification used to describe functional liver anatomy), the liver was divided into 8 segments: caudate, left superolateral, left inferolateral, left superomedial (4a), left inferomedial (4b), right anteroinferior, right posteroinferior, right posterosuperior and right anterosuperior. |
| Change From Baseline in Liver Fat Content at Month 4 | Baseline and Month 4 | Liver fat content was quantitatively measured by evaluating the percentage of PDFF from an abdominal MRI. On the basis of Couinaud classification (a classification used to describe functional liver anatomy), the liver was divided into 8 segments: caudate, left superolateral, left inferolateral, left superomedial (4a), left inferomedial (4b), right anteroinferior, right posteroinferior, right posterosuperior and right anterosuperior. |
Countries
United States
Participant flow
Recruitment details
Participants took part at 11 sites in the United States from 26 April 2013 to 30 September 2014.
Pre-assignment details
Participants with a historical diagnosis of nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) activity score (NAS) of greater than or equal to (\>=) 3 were enrolled in 1 of 3 treatment groups as follows: roflumilast + pioglitazone; roflumilast only; pioglitazone only.
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast + Pioglitazone Roflumilast, 500 microgram (mcg), tablet, orally, once daily and pioglitazone, 30 milligram (mg), tablet, orally, once daily for up to 4 months. | 7 |
| Roflumilast Only Roflumilast, 500 mcg, tablet, orally, once daily and pioglitazone placebo-matching tablet, orally, once daily for up to 4 months. | 7 |
| Pioglitazone Only Pioglitazone, 30 mg, tablet, orally, once daily and roflumilast placebo-matching tablet, orally, once daily for up to 4 months. | 6 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Study Termination | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Roflumilast + Pioglitazone | Total | Pioglitazone Only | Roflumilast Only |
|---|---|---|---|---|
| Age, Continuous | 45.4 years STANDARD_DEVIATION 9.64 | 44.0 years STANDARD_DEVIATION 10.93 | 42.5 years STANDARD_DEVIATION 8.67 | 43.9 years STANDARD_DEVIATION 14.77 |
| Age, Customized 18 - 39 years | 3 participants | 8 participants | 3 participants | 2 participants |
| Age, Customized 40 - 59 years | 4 participants | 11 participants | 3 participants | 4 participants |
| Age, Customized 60 - 80 years | 0 participants | 1 participants | 0 participants | 1 participants |
| Body Mass Index (BMI) | 37.18 kilogram per square meter(kg/m^2) STANDARD_DEVIATION 5.192 | 35.26 kilogram per square meter(kg/m^2) STANDARD_DEVIATION 6.381 | 36.60 kilogram per square meter(kg/m^2) STANDARD_DEVIATION 7.475 | 32.19 kilogram per square meter(kg/m^2) STANDARD_DEVIATION 6.189 |
| Gender Female | 5 Participants | 9 Participants | 2 Participants | 2 Participants |
| Gender Male | 2 Participants | 11 Participants | 4 Participants | 5 Participants |
| Height | 165.6 centimeter (cm) STANDARD_DEVIATION 15.13 | 169.3 centimeter (cm) STANDARD_DEVIATION 11.13 | 174.3 centimeter (cm) STANDARD_DEVIATION 7.5 | 168.7 centimeter (cm) STANDARD_DEVIATION 8.62 |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 4 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic or Latino | 7 participants | 16 participants | 5 participants | 4 participants |
| Race/Ethnicity, Customized White | 7 participants | 17 participants | 6 participants | 4 participants |
| Region of Enrollment United States | 7 participants | 20 participants | 6 participants | 7 participants |
| Smoking Classification Current Smoker | 1 participants | 3 participants | 1 participants | 1 participants |
| Smoking Classification Ex-Smoker | 3 participants | 3 participants | 0 participants | 0 participants |
| Smoking Classification Had Never Smoked | 3 participants | 14 participants | 5 participants | 6 participants |
| Type 2 Diabetes Mellitus Did Not Have Diabetes Mellitus | 5 participants | 15 participants | 5 participants | 5 participants |
| Type 2 Diabetes Mellitus Had Diabetes Mellitus | 2 participants | 5 participants | 1 participants | 2 participants |
| Weight | 102.19 kilogram (kg) STANDARD_DEVIATION 21.041 | 101.03 kilogram (kg) STANDARD_DEVIATION 19.887 | 110.15 kilogram (kg) STANDARD_DEVIATION 15.456 | 92.06 kilogram (kg) STANDARD_DEVIATION 20.784 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 4 / 7 | 4 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 6 |
Outcome results
Primary
Amount of Serum Alanine Transaminase (ALT) at Baseline
Time frame: Baseline
Population: Safety analysis set included all participants who were randomized, received at least 1 dose of double-blind study medication and had baseline assessment available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast + Pioglitazone | Amount of Serum Alanine Transaminase (ALT) at Baseline | 101.7 international units per liter (IU/L) | Standard Deviation 56.98 |
| Roflumilast Only | Amount of Serum Alanine Transaminase (ALT) at Baseline | 83.4 international units per liter (IU/L) | Standard Deviation 31.63 |
| Pioglitazone Only | Amount of Serum Alanine Transaminase (ALT) at Baseline | 118.8 international units per liter (IU/L) | Standard Deviation 36.76 |
Primary
Percent Change From Baseline in Serum ALT at Month 4
The percent change between the serum ALT value collected at Month 4 or final visit relative to baseline.
Time frame: Month 4
Population: Safety analysis set included all participants who were randomized, received at least 1 dose of double-blind study medication and had baseline and at least 1 post-baseline assessment available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast + Pioglitazone | Percent Change From Baseline in Serum ALT at Month 4 | -53.89 percent change | Standard Deviation 23.362 |
| Roflumilast Only | Percent Change From Baseline in Serum ALT at Month 4 | -56.22 percent change | Standard Deviation 6.014 |
| Pioglitazone Only | Percent Change From Baseline in Serum ALT at Month 4 | -28.86 percent change | Standard Deviation 53.298 |
Secondary
Amount of Serum Aspartate Transaminase (AST) at Baseline
Time frame: Baseline
Population: Safety analysis set included all participants who were randomized, received at least 1 dose of double-blind study medication and had baseline assessment available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast + Pioglitazone | Amount of Serum Aspartate Transaminase (AST) at Baseline | 64.0 IU/L | Standard Deviation 43.49 |
| Roflumilast Only | Amount of Serum Aspartate Transaminase (AST) at Baseline | 44.9 IU/L | Standard Deviation 15.25 |
| Pioglitazone Only | Amount of Serum Aspartate Transaminase (AST) at Baseline | 88.3 IU/L | Standard Deviation 73.06 |
Secondary
Change From Baseline in Liver Fat Content at Month 4
Liver fat content was quantitatively measured by evaluating the percentage of PDFF from an abdominal MRI. On the basis of Couinaud classification (a classification used to describe functional liver anatomy), the liver was divided into 8 segments: caudate, left superolateral, left inferolateral, left superomedial (4a), left inferomedial (4b), right anteroinferior, right posteroinferior, right posterosuperior and right anterosuperior.
Time frame: Baseline and Month 4
Population: Safety analysis set included all participants who were randomized, received at least 1 dose of double-blind study medication and had baseline and at least 1 post-baseline assessment available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Left superomedial: (n= 3, 3, 3) | -14.687 percent change in PDFF | Standard Deviation 13.6909 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Right anterosuperior: (n=3, 3, 3) | -16.127 percent change in PDFF | Standard Deviation 13.982 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Right anteroinferior: (n= 3, 3, 3) | -13.990 percent change in PDFF | Standard Deviation 13.1266 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Left inferomedial: (n= 3, 3, 3) | -14.107 percent change in PDFF | Standard Deviation 15.2957 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Caudate; (n= 3, 3, 3) | -18.787 percent change in PDFF | Standard Deviation 11.5646 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Right posterosuperior: (n=3, 3, 3) | -17.717 percent change in PDFF | Standard Deviation 13.0691 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Left inferolateral; (n= 3, 3, 3) | -14.290 percent change in PDFF | Standard Deviation 13.1654 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Left superolateral; (n= 6, 6, 6) | -15.170 percent change in PDFF | Standard Deviation 13.7442 |
| Roflumilast + Pioglitazone | Change From Baseline in Liver Fat Content at Month 4 | Right posteroinferior: (n=3, 3, 3) | -18.073 percent change in PDFF | Standard Deviation 13.147 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Left inferomedial: (n= 3, 3, 3) | -10.977 percent change in PDFF | Standard Deviation 5.0052 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Caudate; (n= 3, 3, 3) | -11.590 percent change in PDFF | Standard Deviation 5.5674 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Left superolateral; (n= 6, 6, 6) | -10.287 percent change in PDFF | Standard Deviation 1.9695 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Left inferolateral; (n= 3, 3, 3) | -10.077 percent change in PDFF | Standard Deviation 2.903 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Left superomedial: (n= 3, 3, 3) | -11.177 percent change in PDFF | Standard Deviation 3.9429 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Right anteroinferior: (n= 3, 3, 3) | -10.260 percent change in PDFF | Standard Deviation 6.9972 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Right posteroinferior: (n=3, 3, 3) | -9.250 percent change in PDFF | Standard Deviation 1.6808 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Right posterosuperior: (n=3, 3, 3) | -9.797 percent change in PDFF | Standard Deviation 4.4053 |
| Roflumilast Only | Change From Baseline in Liver Fat Content at Month 4 | Right anterosuperior: (n=3, 3, 3) | -9.803 percent change in PDFF | Standard Deviation 3.3661 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Left inferolateral; (n= 3, 3, 3) | -8.773 percent change in PDFF | Standard Deviation 7.0821 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Caudate; (n= 3, 3, 3) | -10.287 percent change in PDFF | Standard Deviation 8.8098 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Right posteroinferior: (n=3, 3, 3) | -8.790 percent change in PDFF | Standard Deviation 10.2188 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Left superolateral; (n= 6, 6, 6) | -8.067 percent change in PDFF | Standard Deviation 7.6318 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Right anterosuperior: (n=3, 3, 3) | -8.647 percent change in PDFF | Standard Deviation 10.1658 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Left inferomedial: (n= 3, 3, 3) | -9.417 percent change in PDFF | Standard Deviation 8.936 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Left superomedial: (n= 3, 3, 3) | -9.217 percent change in PDFF | Standard Deviation 8.7999 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Right posterosuperior: (n=3, 3, 3) | -8.113 percent change in PDFF | Standard Deviation 10.4166 |
| Pioglitazone Only | Change From Baseline in Liver Fat Content at Month 4 | Right anteroinferior: (n= 3, 3, 3) | -7.693 percent change in PDFF | Standard Deviation 9.7985 |
Secondary
Liver Fat Content at Baseline
Liver fat content was quantitatively measured by evaluating the percentage of proton density fat fraction (PDFF) from an abdominal magnetic resonance imaging (MRI). On the basis of Couinaud classification (a classification used to describe functional liver anatomy), the liver was divided into 8 segments: caudate, left superolateral, left inferolateral, left superomedial (4a), left inferomedial (4b), right anteroinferior, right posteroinferior, right posterosuperior and right anterosuperior.
Time frame: Baseline
Population: Safety analysis set included all participants who were randomized, received at least 1 dose of double-blind study medication and had baseline assessment available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Right posteroinferior: (n= 6, 7, 6) | 23.710 percentage of PDFF | Standard Deviation 8.6478 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Left inferolateral; (n= 6, 7, 6) | 22.385 percentage of PDFF | Standard Deviation 8.9894 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Right posterosuperior: (n= 6, 7, 6) | 23.282 percentage of PDFF | Standard Deviation 9.5984 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Right anterosuperior: (n=6, 7, 6) | 23.630 percentage of PDFF | Standard Deviation 8.7454 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Left superomedial: (n= 6, 7, 6) | 22.115 percentage of PDFF | Standard Deviation 9.7126 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Caudate; (n= 6, 7, 6) | 22.233 percentage of PDFF | Standard Deviation 8.275 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Left inferomedial: (n= 6, 6, 6) | 21.553 percentage of PDFF | Standard Deviation 9.5912 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Left superolateral; (n= 6, 6, 6) | 19.485 percentage of PDFF | Standard Deviation 8.808 |
| Roflumilast + Pioglitazone | Liver Fat Content at Baseline | Right anteroinferior: (n= 6, 7, 6) | 22.478 percentage of PDFF | Standard Deviation 9.0548 |
| Roflumilast Only | Liver Fat Content at Baseline | Left inferomedial: (n= 6, 6, 6) | 18.977 percentage of PDFF | Standard Deviation 8.697 |
| Roflumilast Only | Liver Fat Content at Baseline | Right posteroinferior: (n= 6, 7, 6) | 18.804 percentage of PDFF | Standard Deviation 6.6882 |
| Roflumilast Only | Liver Fat Content at Baseline | Left superomedial: (n= 6, 7, 6) | 20.426 percentage of PDFF | Standard Deviation 7.917 |
| Roflumilast Only | Liver Fat Content at Baseline | Right anteroinferior: (n= 6, 7, 6) | 19.994 percentage of PDFF | Standard Deviation 9.0103 |
| Roflumilast Only | Liver Fat Content at Baseline | Right posterosuperior: (n= 6, 7, 6) | 18.870 percentage of PDFF | Standard Deviation 7.5764 |
| Roflumilast Only | Liver Fat Content at Baseline | Left inferolateral; (n= 6, 7, 6) | 19.747 percentage of PDFF | Standard Deviation 7.8306 |
| Roflumilast Only | Liver Fat Content at Baseline | Left superolateral; (n= 6, 6, 6) | 17.813 percentage of PDFF | Standard Deviation 7.441 |
| Roflumilast Only | Liver Fat Content at Baseline | Right anterosuperior: (n=6, 7, 6) | 19.786 percentage of PDFF | Standard Deviation 8.5929 |
| Roflumilast Only | Liver Fat Content at Baseline | Caudate; (n= 6, 7, 6) | 19.107 percentage of PDFF | Standard Deviation 7.799 |
| Pioglitazone Only | Liver Fat Content at Baseline | Right anterosuperior: (n=6, 7, 6) | 21.527 percentage of PDFF | Standard Deviation 9.6648 |
| Pioglitazone Only | Liver Fat Content at Baseline | Caudate; (n= 6, 7, 6) | 20.117 percentage of PDFF | Standard Deviation 9.8492 |
| Pioglitazone Only | Liver Fat Content at Baseline | Left inferolateral; (n= 6, 7, 6) | 19.153 percentage of PDFF | Standard Deviation 10.5909 |
| Pioglitazone Only | Liver Fat Content at Baseline | Left superomedial: (n= 6, 7, 6) | 20.100 percentage of PDFF | Standard Deviation 9.8688 |
| Pioglitazone Only | Liver Fat Content at Baseline | Left inferomedial: (n= 6, 6, 6) | 21.530 percentage of PDFF | Standard Deviation 9.5193 |
| Pioglitazone Only | Liver Fat Content at Baseline | Right anteroinferior: (n= 6, 7, 6) | 20.742 percentage of PDFF | Standard Deviation 8.7829 |
| Pioglitazone Only | Liver Fat Content at Baseline | Right posteroinferior: (n= 6, 7, 6) | 20.070 percentage of PDFF | Standard Deviation 9.9727 |
| Pioglitazone Only | Liver Fat Content at Baseline | Right posterosuperior: (n= 6, 7, 6) | 19.943 percentage of PDFF | Standard Deviation 8.9666 |
| Pioglitazone Only | Liver Fat Content at Baseline | Left superolateral; (n= 6, 6, 6) | 17.278 percentage of PDFF | Standard Deviation 7.2225 |
Secondary
Percent Change From Baseline in Serum AST at Month 4
The percent change between the serum AST value collected at Month 4 or final visit relative to baseline.
Time frame: Month 4
Population: Safety analysis set included all participants who were randomized, received at least 1 dose of double-blind study medication and had baseline and at least 1 post-baseline assessment available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast + Pioglitazone | Percent Change From Baseline in Serum AST at Month 4 | -41.31 percent change | Standard Deviation 36.087 |
| Roflumilast Only | Percent Change From Baseline in Serum AST at Month 4 | -43.20 percent change | Standard Deviation 7.339 |
| Pioglitazone Only | Percent Change From Baseline in Serum AST at Month 4 | -17.56 percent change | Standard Deviation 45.458 |