Diabetes Mellitus, Type 2, NASH - Nonalcoholic Steatohepatitis
Conditions
Brief summary
This is a double-blind, randomized, placebo-controlled, multi-center study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM.
Detailed description
This is a double-blind, randomized, placebo-controlled, multi-center study using the oral ORMD-0801 insulin formulation in patients with NASH and confirmed type 2 DM. The study will consist of a Screening Phase, Placebo Run-in Phase, Treatment Phase and an End-of-Study Phase. Approximately 36 subjects will be randomized in a 2:1 ratio to receive either 8 mg ORMD-0801, 1 capsule twice a day (once in the morning approximately 30 to 45 minutes prior to breakfast and no later than 10 AM, and once at night between 8 PM to Midnight and no sooner than 1 hour after dinner) or matching placebo.
Interventions
DRUGORMD-0801 (Insulin) capsule 8 mg BD
8 mg ORMD-0801, 1 capsule, twice a day, once in the morning and once in the evening.
OTHERPlacebo
Matching Placebo
Sponsors
Integrium
Oramed, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The study will consist of a Screening Phase, Placebo Run-in Phase, Treatment Phase, and an End-of-Study Phase. Approximately 36 subjects will be randomized in a 2:1 ratio to receive either 8 mg ORMD-0801, 1 capsule twice a day (once in the morning approximately 30 to 45 minutes prior to breakfast and no later than 10 AM, and once at night between 8 PM to Midnight and no sooner than 1 hour after dinner) or matching placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female aged 18-70 years. * BMI ≥25 * Known type 2 DM according to American Diabetic Association (one of the three needed): Fasting Plasma Glucose ≥126 mg/dl or 2h postprandial (PG) following 75g OGTT ≥200 mg/dl or HbA1c \> 6.5%28 or on treatment with metformin only or metformin in addition to no more than two of the following medications sulfonylurea, DPP-4 inhibitors, GLP-1 receptor agonists, Thiazolidinediones (TZDs) * Diagnosis of NAFLD by non-invasive determination of hepatic steatosis grade S1, defined as hepatic steatosis\>8% by MRI- PDFF and CAP FibroScan ≥ 238 dB/m. * Liver enzyme abnormalities: ULN≤5 times. * Fibrosis score 21≤F≤3 as defined by FibroScan measurement (Liver stiffness measurement, LSM) of 6 ≤ LSM ≤ 12 kPa. * Signature of the written informed consent. * Negative urine serum pregnancy test at Screening study entry for females of childbearing potential (WCBP). * WCBP must have a negative urine pregnancy test result prior to the start of the run-in period and initiation if active dosing. A negative urine and serum pregnancy test must be obtained prior to active dosing. Males and females of childbearing potential must use two methods of contraception (double barrier method), one of which must be an acceptable barrier method from the time of screening to the last dosing study visit (22 weeks). Barrier methods of contraception include male condoms plus spermicide, diaphragm with spermicide plus male condom, cervical cap with spermicide plus male condom, or oral contraceptives. Acceptable methods of birth control include abstinence, oral contraceptives, surgical sterilization, vasectomy, the contraceptive patch, and the contraceptive ring. If a subject is not usually sexually active but becomes active, he or his partner should use medically accepted forms of contraception. Sperm donations will not be allowed for the duration of the study and for 90 days after the last dose of study drug. * Females of non-childbearing potential are defined as postmenopausal who a) had more than 24 months since last menstrual cycle with menopausal levels of FSH (FSH Level \> 40), b) who are surgically menopausal (surgical sterility defined by tubal occlusion, bilateral oophorectomy, bilateral salpingectomy or hysterectomy). * For hypertensive patients, hypertension must be controlled by a stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study) with BP \< 150/\<95 mmHg * Patients previously treated with vitamin E (\>400IU/day), Polyunsaturated fatty acid (\>2g/day) or Ursodeoxycholic acid fish oil can be included if drugs are stopped at least 3 months prior to enrolment and up to the end of the study. * Glycaemia must be controlled (Glycosylated Hemoglobin A1C ≤8.5%) while any HbA1C increment should not exceed 1% during 6 months prior to enrolment).
Exclusion criteria
* Patients with active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, genetic hemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, alcohol liver disease, drug-induced liver disease) at the time of enrolment. * ALT or AST \> 5 times ULN. * Abnormal synthetic liver function (serum albumin ≤3.5gm%, INR \>1.3). * Known alcohol and/or any other drug abuse or dependence in the last five years. * Weight \>120 Kg (264.6 lbs.) * Known history or presence of clinically significant, cardiovascular, gastrointestinal, metabolic (other than diabetes mellitus), neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder, or nephrotic syndrome. * History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolites (e.g. inflammatory bowel disease (IBD), previous intestinal (ileal or colonic) operation, chronic pancreatitis, celiac disease, or previous vagotomy. * Weight loss of more than 5% within 6 months prior to enrolment. * History of bariatric surgery. * Uncontrolled blood pressure BP ≥150/≥95. * Non-type 2 DM (type 1, endocrinopathy, genetic syndromes etc.). * Patients with HIV. * Daily alcohol intake \>20 g/day (2 units/day) for women and \>30 g/day (3 units/day) for men. * Treatment with anti-diabetic medications other than metformin and more than two of the following medications sulfonylurea, DPP-4 inhibitors, GLP-1 receptor agonists, TZDs * Metformin, fibrates, statins, not provided on a stable dose in the last 6 months. * Patients who are treated with valproic acid, Tamoxifen, methotrexate, amiodarone. * Chronic treatment with antibiotics (e.g. Rifaximin). * Homeopathic and/or Alternative treatments. Any treatment must be stopped before the screening period. * Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone \>2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted. * Patients with renal dysfunction: eGFR\< 40 ml/min. * Unexplained serum creatinine phosphokinase (CPK) \>3X the upper limit of normal (ULN). Patients with a reason for CPK elevation may have the measurement repeated prior to enrolment; a CPK retest \> 3X ULN leads to exclusion. * Subjects meeting criteria for contraindication for MRI - including the following: i. History of severe claustrophobia impacting the ability to perform MRI during the study, even despite mild sedation/treatment with as anxiolytic. ii. Subjects with metal implants, devices, paramagnetic objects contained within the body, and excessive or metal-containing tattoos. iii. Subjects unable to lie still within the environment of the MRI scanner or maintain a breath-hold for the required period to acquire images, even despite mild sedation/treatment with an anxiolytic. * The subject participated in a clinical research study involving a new chemical entity within 4 weeks of study entry. * Known allergy to soy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Events | Screening through Week 16 | The Number of Treatment-Emergent Adverse Events (TEAE) according to CTCAE version 4.03. A TEAE is an adverse event for which the start date is on or after the date that the treatment began. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline of Median MRPDFF of Whole Liver | Baseline and Week 12 (Visit 8) | The percent change in MR PDFF from baseline to Week 12 of Whole Liver |
| Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | Baseline and Week 12 | Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver at Baseline and Week12. The Whole liver was delineated by a central radiologist. The liver was subdivided into 8 sections according to the Coinaud liver segmentation for MRI. |
| Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | Screening and Week 12 (Visit 8) | The percent change from basline in liver fat content as measured by the mean MRI Proton density Fat Fraction (MR PDFF) at baseline and at week 12 of Whole Liver |
| Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 | Baseline and Week 12 (Visit 8) | Median MRPDFF (percentage fat in the liver) of liver segment 3 as measured by MRI Proton Density Fat Fraction at baseline and at week 12. Delineation by a central radiologist of the Liver Segment 3 in the slice with the largest Liver Segment 3 cross-section. |
| Percent Change From Baseline of Median MRPDFF of Liver Segment 3 | Baseline and Week 12 (Visit 8) | Percent Change from Baseline Median MRPDFF of Liver Segment measured at baseline and Week 12 (Visit 8) |
| Mean MRPDFF of Liver Segment 3 | Baseline and Week 12 (Visit 8) | Mean MRPDFF of Liver Segment measured at baseline and Week 12 |
| Percent Change of Mean MRPDFF of Liver Segment 3 | Baseline and Week 12 (Visit 8) | Percent change from baseline of mean MR PDFF measurement of liver segment 3 at baseline and week 12 |
| Median MR PDFF of Liver Segment 6 | Screening and Week 12 (Visit 8) | Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8). Delineation by a central radiologist of Liver Segment 6 in the slice with the largest Liver Segment 6 cross-section. |
| Percent Change From Baseline of Median MR PDFF of Liver Segment 6 | Screening and Week 12 (Visit 8) | Percent Change from Baseline of Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 |
| Median MRPDFF at Baseline and Week 12 of Whole Liver | Baseline and Week 12 (Visit 8) | Median MRPDFF at Baseline and Week 12 of Whole Liver. Delineation by a central radiologist of the whole liver in the slice with the largest liver cross-section. The Liver was subdivided into 8 sections according to the Coinaud liver segmentation for MRI. |
| Percent Change From Baseline of Mean MR PDFF of Liver Segment 6 | Screening and Week 12 (Visit 8) | Percent Change from Baseline Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8) |
| Median MRPDFF of Liver Segment 8 | Baseline and Week 12 (Visit 8) | Median MRPDFF of Liver Segment 8 measured at baseline and Week 12 (Visit 8) |
| Percent Change in Median MRPDFF of Liver Segment 8 | Baseline and Week 12 (Visit 8) | Percent change from baseline in median MRPDFF of Liver segment 8 measured at baseline and week 12 (Visit 8). |
| Mean MRPDFF of Liver Segment 8 | Baseline and Week 12 (Visit 8) | Liver fat percentage of liver segment 8 as measured by MRI Proton Density Fat Fraction (MR PDFF) at baseline and at week 12 (Visit 8). Delineation by a central radiologist of Liver Segment 8 in the slice with the largest Liver Segment 8 cross-section. |
| Percent Change From Baseline in Mean MRPDFF of Liver Segment 8 | Baseline and Week 12 (Visit 8) | Percent change from baseline in MRPDFF of liver segment 8 at baseline and at week 12 (Visit 8) |
| Liver Steatosis | Baseline and Week 12 (Visit 8) | Liver steatosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M) |
| Change in Liver Steatosis From Baseline | Baseline and Week 12 (Visit 8) | Change in Liver steatosis from baseline measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M) |
| Liver Fibrosis | Baseline and Week 12 (Visit 8) | Liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa). |
| Change From Baseline of Liver Fibrosis | Baseline and Week 12 (Visit 8) | The change from baseline in liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa). |
| Mean MR PDFF of Liver Segment 6 | Screening and Week 12 (Visit 8) | Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8) |
Countries
Israel, United States
Participant flow
Pre-assignment details
All screened participants must have an MRI scan prior to enrollment to confirm satisfying the entry criteria of MR PDFF \>= 8%
Participants by arm
| Arm | Count |
|---|---|
| Placebo Fish oil
Placebo: Matching Placebo | 11 |
| ORMD-0801 (Insulin) Capsule 8 mg BD ORMD-0801 (insulin) capsule Dose: 8 mg BD Dosage Regimen: 1 capsule twice a day (once in the morning approximately 30 to 45 minutes prior to breakfast and no later than 10 AM, and once at night between 8 PM to Midnight and no sooner than 1 hour after dinner) Mode of Administration: Oral
ORMD-0801 (Insulin) capsule 8 mg BD: 8 mg ORMD-0801, 1 capsule, twice a day, once in the morning and once in the evening. | 21 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | ORMD-0801 (Insulin) Capsule 8 mg BD | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.67 Years STANDARD_DEVIATION 7.565 | 56.73 Years STANDARD_DEVIATION 10.355 | 58.00 Years STANDARD_DEVIATION 8.508 |
| Body Mass Index (BMI) | 33.567 Kg/m^2 STANDARD_DEVIATION 5.2981 | 32.109 Kg/m^2 STANDARD_DEVIATION 4.5496 | 33.066 Kg/m^2 STANDARD_DEVIATION 5.0281 |
| Childbearing Status At least 24 months Post-Menopausal | 3 Participants | 3 Participants | 6 Participants |
| Childbearing Status Not Applicable | 14 Participants | 6 Participants | 20 Participants |
| Childbearing Status Of Childbearing Potential | 0 Participants | 0 Participants | 0 Participants |
| Childbearing Status Surgically Sterilized | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 7 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 4 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Median Magnetic Resonance Proton Fat Fraction (MRPDFF) | 13.900 percent liver fat | 21.100 percent liver fat | 14.250 percent liver fat |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 21 |
| other Total, other adverse events | 4 / 11 | 7 / 21 |
| serious Total, serious adverse events | 1 / 11 | 1 / 21 |
Outcome results
Primary
Number of Treatment-Emergent Adverse Events
The Number of Treatment-Emergent Adverse Events (TEAE) according to CTCAE version 4.03. A TEAE is an adverse event for which the start date is on or after the date that the treatment began.
Time frame: Screening through Week 16
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Treatment-Emergent Adverse Events | 0 Adverse Events |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Number of Treatment-Emergent Adverse Events | 2 Adverse Events |
Secondary
Change From Baseline of Liver Fibrosis
The change from baseline in liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).
Time frame: Baseline and Week 12 (Visit 8)
Population: Safety Population. One subject did not have a Visit 8 Fibroscan (discontinued study due to Withdrew Consent)~A second subject did not have a Visit 8 Fibroscan (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change From Baseline of Liver Fibrosis | 0.3 kPa (kilo Pascals) |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Change From Baseline of Liver Fibrosis | -0.8 kPa (kilo Pascals) |
Secondary
Change in Liver Steatosis From Baseline
Change in Liver steatosis from baseline measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M)
Time frame: Baseline and Week 12 (Visit 8)
Population: Safety Population. One subject did not have a Visit 8 Fibroscan (discontinued study due to Withdrew Consent)~A second subject did not have a Visit 8 Fibroscan (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Liver Steatosis From Baseline | 13.0 dB/M |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Change in Liver Steatosis From Baseline | -16.0 dB/M |
Secondary
Liver Fibrosis
Liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).
Time frame: Baseline and Week 12 (Visit 8)
Population: Safety Population. One subject did not have a Visit 8 Fibroscan (discontinued study due to Withdrew Consent)~A second subject did not have a Visit 8 Fibroscan (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Liver Fibrosis | Median Liver Fibrosis Baseline | 8.4 kPa (kilo Pascals) |
| Placebo | Liver Fibrosis | Median Liver Fibrosis Week 12 | 7.4 kPa (kilo Pascals) |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Liver Fibrosis | Median Liver Fibrosis Baseline | 8.6 kPa (kilo Pascals) |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Liver Fibrosis | Median Liver Fibrosis Week 12 | 7.4 kPa (kilo Pascals) |
Secondary
Liver Steatosis
Liver steatosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M)
Time frame: Baseline and Week 12 (Visit 8)
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Liver Steatosis | Median Liver Steatosis Baseline | 335 dB/M |
| Placebo | Liver Steatosis | Median Liver Steatosis Week 12 | 345.0 dB/M |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Liver Steatosis | Median Liver Steatosis Baseline | 329 dB/M |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Liver Steatosis | Median Liver Steatosis Week 12 | 329.0 dB/M |
Secondary
Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver
Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver at Baseline and Week12. The Whole liver was delineated by a central radiologist. The liver was subdivided into 8 sections according to the Coinaud liver segmentation for MRI.
Time frame: Baseline and Week 12
Population: Intent-to-Treat. Placebo population: One subject's baseline Whole Liver MRPDFF was missing. This patient did have their Visit 8 MRI, however since there was no baseline MRPDFF Whole Liver, the change from baseline measurement cannot be calculated. A second patient did not have their Visit 8 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | Mean MRPDFF of Whole Liver at Baseline | 21.558 percentage of fat | Standard Deviation 8.2072 |
| Placebo | Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | Mean MR PDFF of Whole Liver at Week 12 | 17.414 percentage of fat | Standard Deviation 8.6331 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | Mean MRPDFF of Whole Liver at Baseline | 15.683 percentage of fat | Standard Deviation 6.1605 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | Mean MR PDFF of Whole Liver at Week 12 | 14.274 percentage of fat | Standard Deviation 6.8032 |
Secondary
Mean MRPDFF of Liver Segment 3
Mean MRPDFF of Liver Segment measured at baseline and Week 12
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean MRPDFF of Liver Segment 3 | MRPDFF of Liver Segment 3 at baseline | 20.617 percentage fat | Standard Deviation 9.1032 |
| Placebo | Mean MRPDFF of Liver Segment 3 | MR PDFF of Liver Segment 3 at Week 12 | 16.610 percentage fat | Standard Deviation 9.2736 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean MRPDFF of Liver Segment 3 | MRPDFF of Liver Segment 3 at baseline | 14.560 percentage fat | Standard Deviation 5.3974 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean MRPDFF of Liver Segment 3 | MR PDFF of Liver Segment 3 at Week 12 | 13.119 percentage fat | Standard Deviation 6.2239 |
Secondary
Mean MR PDFF of Liver Segment 6
Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8)
Time frame: Screening and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 6 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean MR PDFF of Liver Segment 6 | Mean MRPDFF of liver segment 6 at Baseline | 22.174 percentage liver fat | Standard Deviation 8.9629 |
| Placebo | Mean MR PDFF of Liver Segment 6 | Mean MRPDFF of Liver segment 6 at Week 12 | 16.226 percentage liver fat | Standard Deviation 8.4452 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean MR PDFF of Liver Segment 6 | Mean MRPDFF of Liver segment 6 at Week 12 | 14.009 percentage liver fat | Standard Deviation 7.1855 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean MR PDFF of Liver Segment 6 | Mean MRPDFF of liver segment 6 at Baseline | 15.828 percentage liver fat | Standard Deviation 7.3523 |
Secondary
Mean MRPDFF of Liver Segment 8
Liver fat percentage of liver segment 8 as measured by MRI Proton Density Fat Fraction (MR PDFF) at baseline and at week 12 (Visit 8). Delineation by a central radiologist of Liver Segment 8 in the slice with the largest Liver Segment 8 cross-section.
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 8 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean MRPDFF of Liver Segment 8 | Mean MRPDFF of liver segment 8 at Baseline | 22.565 percentage fat | Standard Deviation 7.8978 |
| Placebo | Mean MRPDFF of Liver Segment 8 | Mean MRPDFF of Liver segment 8 at Week 12 | 17.451 percentage fat | Standard Deviation 2.8338 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean MRPDFF of Liver Segment 8 | Mean MRPDFF of liver segment 8 at Baseline | 16.071 percentage fat | Standard Deviation 6.3147 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Mean MRPDFF of Liver Segment 8 | Mean MRPDFF of Liver segment 8 at Week 12 | 14.817 percentage fat | Standard Deviation 7.1945 |
Secondary
Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3
Median MRPDFF (percentage fat in the liver) of liver segment 3 as measured by MRI Proton Density Fat Fraction at baseline and at week 12. Delineation by a central radiologist of the Liver Segment 3 in the slice with the largest Liver Segment 3 cross-section.
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 3 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 | Median MRPDFF Liver Segment 3 Baseline | 21.10 percentage fat |
| Placebo | Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 | Median MRPDFF Liver Segment 3 Week 12 | 15.150 percentage fat |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 | Median MRPDFF Liver Segment 3 Baseline | 13.900 percentage fat |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 | Median MRPDFF Liver Segment 3 Week 12 | 11.900 percentage fat |
Secondary
Median MRPDFF at Baseline and Week 12 of Whole Liver
Median MRPDFF at Baseline and Week 12 of Whole Liver. Delineation by a central radiologist of the whole liver in the slice with the largest liver cross-section. The Liver was subdivided into 8 sections according to the Coinaud liver segmentation for MRI.
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Whole Liver MRPDFF was missing. This patient did have their Visit 8 MRI, however since there was no baseline MRPDFF Whole Liver, the change from baseline measurement cannot be calculated. A second patient did not have their Visit 8 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median MRPDFF at Baseline and Week 12 of Whole Liver | Median MRPDFF at Baseline | 24.350 Percent fat (MRPDFF) |
| Placebo | Median MRPDFF at Baseline and Week 12 of Whole Liver | Median MRPDFF (percentage fat) at Week 12 | 17.300 Percent fat (MRPDFF) |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median MRPDFF at Baseline and Week 12 of Whole Liver | Median MRPDFF at Baseline | 15.340 Percent fat (MRPDFF) |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median MRPDFF at Baseline and Week 12 of Whole Liver | Median MRPDFF (percentage fat) at Week 12 | 13.300 Percent fat (MRPDFF) |
Secondary
Median MR PDFF of Liver Segment 6
Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8). Delineation by a central radiologist of Liver Segment 6 in the slice with the largest Liver Segment 6 cross-section.
Time frame: Screening and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 6 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median MR PDFF of Liver Segment 6 | Median MRPDFF of Liver Segment 6 Baseline | 22.900 percentage of liver fat |
| Placebo | Median MR PDFF of Liver Segment 6 | Median MRPDFF of Liver Segment 6 Week 12 | 15.400 percentage of liver fat |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median MR PDFF of Liver Segment 6 | Median MRPDFF of Liver Segment 6 Baseline | 15.420 percentage of liver fat |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median MR PDFF of Liver Segment 6 | Median MRPDFF of Liver Segment 6 Week 12 | 12.600 percentage of liver fat |
Secondary
Median MRPDFF of Liver Segment 8
Median MRPDFF of Liver Segment 8 measured at baseline and Week 12 (Visit 8)
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 8 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median MRPDFF of Liver Segment 8 | Median MRPDFF of Liver Segment 8 at baseline | 25.100 percentage liver fat |
| Placebo | Median MRPDFF of Liver Segment 8 | Median MR PDFF of Liver Segment 8 at Week 12 | 18.200 percentage liver fat |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median MRPDFF of Liver Segment 8 | Median MRPDFF of Liver Segment 8 at baseline | 15.600 percentage liver fat |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Median MRPDFF of Liver Segment 8 | Median MR PDFF of Liver Segment 8 at Week 12 | 13.500 percentage liver fat |
Secondary
Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver
The percent change from basline in liver fat content as measured by the mean MRI Proton density Fat Fraction (MR PDFF) at baseline and at week 12 of Whole Liver
Time frame: Screening and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Whole Liver MRPDFF was missing. This patient did have their Visit 8 MRI, however since there was no baseline MRPDFF Whole Liver, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | -6.526 Percentage of change in MRPDFF | Standard Deviation 15.3158 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change From Baseline in Mean Magnetic Resonance Proton Density Fat Fraction (MRPDFF) of Whole Liver | -7.489 Percentage of change in MRPDFF | Standard Deviation 27.3972 |
Secondary
Percent Change From Baseline in Mean MRPDFF of Liver Segment 8
Percent change from baseline in MRPDFF of liver segment 8 at baseline and at week 12 (Visit 8)
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 8 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Mean MRPDFF of Liver Segment 8 | 17.451 percentage change in MRPDFF | Standard Deviation 8.6343 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change From Baseline in Mean MRPDFF of Liver Segment 8 | 14.817 percentage change in MRPDFF | Standard Deviation 7.1945 |
Secondary
Percent Change From Baseline of Mean MR PDFF of Liver Segment 6
Percent Change from Baseline Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8)
Time frame: Screening and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 6 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline of Mean MR PDFF of Liver Segment 6 | -9.891 percent change | Standard Deviation 15.3865 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change From Baseline of Mean MR PDFF of Liver Segment 6 | -9.310 percent change | Standard Deviation 21.7602 |
Secondary
Percent Change From Baseline of Median MRPDFF of Liver Segment 3
Percent Change from Baseline Median MRPDFF of Liver Segment measured at baseline and Week 12 (Visit 8)
Time frame: Baseline and Week 12 (Visit 8)
Population: ntent-to-Treat. Placebo population: One subject's baseline Liver Segment 3 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline of Median MRPDFF of Liver Segment 3 | 0.000 percentage change |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change From Baseline of Median MRPDFF of Liver Segment 3 | -6.424 percentage change |
Secondary
Percent Change From Baseline of Median MR PDFF of Liver Segment 6
Percent Change from Baseline of Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12
Time frame: Screening and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 6 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline of Median MR PDFF of Liver Segment 6 | -4.965 percent change |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change From Baseline of Median MR PDFF of Liver Segment 6 | -6.488 percent change |
Secondary
Percent Change From Baseline of Median MRPDFF of Whole Liver
The percent change in MR PDFF from baseline to Week 12 of Whole Liver
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Whole Liver MRPDFF was missing. This patient did have their Visit 8 MRI, however since there was no baseline MRPDFF Whole Liver, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline of Median MRPDFF of Whole Liver | -1.103 percent change |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change From Baseline of Median MRPDFF of Whole Liver | -7.105 percent change |
Secondary
Percent Change in Median MRPDFF of Liver Segment 8
Percent change from baseline in median MRPDFF of Liver segment 8 measured at baseline and week 12 (Visit 8).
Time frame: Baseline and Week 12 (Visit 8)
Population: Intent-to-Treat. Placebo population: One subject's baseline Liver Segment 8 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change in Median MRPDFF of Liver Segment 8 | -6.376 percent change of the median MRPDFF |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change in Median MRPDFF of Liver Segment 8 | -5.419 percent change of the median MRPDFF |
Secondary
Percent Change of Mean MRPDFF of Liver Segment 3
Percent change from baseline of mean MR PDFF measurement of liver segment 3 at baseline and week 12
Time frame: Baseline and Week 12 (Visit 8)
Population: ntent-to-Treat. Placebo population: One subject's baseline Liver Segment 3 radius was missing. This patient did have their Visit 8 MRI, however since there was baseline data missing, the change from baseline measurement cannot be calculated. A second patient did not have their Week 12 MRI acquired.~ORMD-0801:One subject did not have a Visit 8 MRI (discontinued study due to Withdrew Consent). A second subject did not have a Visit 8 MRI (discontinued study due to Adverse Event)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change of Mean MRPDFF of Liver Segment 3 | 0.105 percentage of Change in MR PDFF | Standard Deviation 17.263 |
| ORMD-0801 (Insulin) Capsule 8 mg BD | Percent Change of Mean MRPDFF of Liver Segment 3 | -10.763 percentage of Change in MR PDFF | Standard Deviation 20.9231 |