Trial Outcomes & Findings for A Study to Assess the Safety and Efficacy of Oral Insulin in T2DM Patients With Nonalcoholic Steatohepatitis (NASH) (NCT NCT04618744)

NCT ID: NCT04618744

Last Updated: 2024-08-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: Screening through Week 16
• Results posted on: 2024-08-07

Participant Flow

All screened participants must have an MRI scan prior to enrollment to confirm satisfying the entry criteria of MR PDFF >= 8%

Participant milestones

Measure	Placebo Fish oil Placebo: Matching Placebo	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.
Overall Study STARTED	11	21
Overall Study COMPLETED	11	19
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Placebo Fish oil Placebo: Matching Placebo	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.
Overall Study Adverse Event	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

A Study to Assess the Safety and Efficacy of Oral Insulin in T2DM Patients With Nonalcoholic Steatohepatitis (NASH)

Baseline characteristics by cohort

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.	Total n=32 Participants Total of all reporting groups
Age, Continuous	56.73 Years STANDARD_DEVIATION 10.355 • n=5 Participants	58.67 Years STANDARD_DEVIATION 7.565 • n=7 Participants	58.00 Years STANDARD_DEVIATION 8.508 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	19 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index (BMI)	32.109 Kg/m^2 STANDARD_DEVIATION 4.5496 • n=5 Participants	33.567 Kg/m^2 STANDARD_DEVIATION 5.2981 • n=7 Participants	33.066 Kg/m^2 STANDARD_DEVIATION 5.0281 • n=5 Participants
Childbearing Status Of Childbearing Potential	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Childbearing Status Surgically Sterilized	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Childbearing Status At least 24 months Post-Menopausal	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Childbearing Status Not Applicable	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Median Magnetic Resonance Proton Fat Fraction (MRPDFF)	21.100 percent liver fat n=5 Participants	13.900 percent liver fat n=7 Participants	14.250 percent liver fat n=5 Participants

PRIMARY outcome

Timeframe: Screening through Week 16

Population: Safety Population

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.

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Number of Treatment-Emergent Adverse Events	0 Adverse Events	2 Adverse Events

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Median MRPDFF at Baseline and Week 12 of Whole Liver Median MRPDFF at Baseline	24.350 Percent fat (MRPDFF) Interval 9.8 to 31.9	15.340 Percent fat (MRPDFF) Interval 5.34 to 27.2
Median MRPDFF at Baseline and Week 12 of Whole Liver Median MRPDFF (percentage fat) at Week 12	17.300 Percent fat (MRPDFF) Interval 3.66 to 29.5	13.300 Percent fat (MRPDFF) Interval 3.33 to 26.8

SECONDARY outcome

Timeframe: 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)

The percent change in MR PDFF from baseline to Week 12 of Whole Liver

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change From Baseline of Median MRPDFF of Whole Liver	-1.103 percent change Interval -28.97 to 16.33	-7.105 percent change Interval -65.78 to 59.18

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=10 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
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	15.683 percentage of fat Standard Deviation 6.1605
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	14.274 percentage of fat Standard Deviation 6.8032

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
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	-7.489 Percentage of change in MRPDFF Standard Deviation 27.3972

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 Median MRPDFF Liver Segment 3 Week 12	15.150 percentage fat Interval 3.11 to 28.7	11.900 percentage fat Interval 3.28 to 26.43
Median Magnetic Resonance Proton Density Fat Fraction (MR PDFF) of Liver Segment 3 Median MRPDFF Liver Segment 3 Baseline	21.10 percentage fat Interval 6.97 to 33.5	13.900 percentage fat Interval 5.34 to 26.9

SECONDARY outcome

Timeframe: 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)

Percent Change from Baseline Median MRPDFF of Liver Segment measured at baseline and Week 12 (Visit 8)

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change From Baseline of Median MRPDFF of Liver Segment 3	0.000 percentage change Interval -26.97 to 26.4	-6.424 percentage change Interval -66.67 to 10.19

SECONDARY outcome

Timeframe: Baseline and Week 12 (Visit 8)

Population: Intent to Treat

Mean MRPDFF of Liver Segment measured at baseline and Week 12

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Mean MRPDFF of Liver Segment 3 MRPDFF of Liver Segment 3 at baseline	20.617 percentage fat Standard Deviation 9.1032	14.560 percentage fat Standard Deviation 5.3974
Mean MRPDFF of Liver Segment 3 MR PDFF of Liver Segment 3 at Week 12	16.610 percentage fat Standard Deviation 9.2736	13.119 percentage fat Standard Deviation 6.2239

SECONDARY outcome

Timeframe: 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)

Percent change from baseline of mean MR PDFF measurement of liver segment 3 at baseline and week 12

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change of Mean MRPDFF of Liver Segment 3	0.105 percentage of Change in MR PDFF Standard Deviation 17.2630	-10.763 percentage of Change in MR PDFF Standard Deviation 20.9231

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Median MR PDFF of Liver Segment 6 Median MRPDFF of Liver Segment 6 Baseline	22.900 percentage of liver fat Interval 8.76 to 37.0	15.420 percentage of liver fat Interval 4.81 to 30.0
Median MR PDFF of Liver Segment 6 Median MRPDFF of Liver Segment 6 Week 12	15.400 percentage of liver fat Interval 3.28 to 27.4	12.600 percentage of liver fat Interval 5.19 to 27.13

SECONDARY outcome

Timeframe: 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)

Percent Change from Baseline of Median Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change From Baseline of Median MR PDFF of Liver Segment 6	-4.965 percent change Interval -37.19 to 15.01	-6.488 percent change Interval -41.49 to 54.63

SECONDARY outcome

Timeframe: 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)

Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8)

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Mean MR PDFF of Liver Segment 6 Mean MRPDFF of liver segment 6 at Baseline	22.174 percentage liver fat Standard Deviation 8.9629	15.828 percentage liver fat Standard Deviation 7.3523
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	14.009 percentage liver fat Standard Deviation 7.1855

SECONDARY outcome

Timeframe: 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)

Percent Change from Baseline Mean Magnetic Resonance Proton Density Fat Fraction of Liver Segment 6 measured at baseline and at week 12 (Visit 8)

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change From Baseline of Mean MR PDFF of Liver Segment 6	-9.891 percent change Standard Deviation 15.3865	-9.310 percent change Standard Deviation 21.7602

SECONDARY outcome

Timeframe: 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)

Median MRPDFF of Liver Segment 8 measured at baseline and Week 12 (Visit 8)

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Median MRPDFF of Liver Segment 8 Median MRPDFF of Liver Segment 8 at baseline	25.100 percentage liver fat Interval 8.06 to 31.2	15.600 percentage liver fat Interval 6.63 to 28.2
Median MRPDFF of Liver Segment 8 Median MR PDFF of Liver Segment 8 at Week 12	18.200 percentage liver fat Interval 3.66 to 27.9	13.500 percentage liver fat Interval 3.27 to 28.03

SECONDARY outcome

Timeframe: 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)

Percent change from baseline in median MRPDFF of Liver segment 8 measured at baseline and week 12 (Visit 8).

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change in Median MRPDFF of Liver Segment 8	-6.376 percent change of the median MRPDFF Interval -35.71 to 12.54	-5.419 percent change of the median MRPDFF Interval -65.18 to 32.75

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Mean MRPDFF of Liver Segment 8 Mean MRPDFF of liver segment 8 at Baseline	22.565 percentage fat Standard Deviation 7.8978	16.071 percentage fat Standard Deviation 6.3147
Mean MRPDFF of Liver Segment 8 Mean MRPDFF of Liver segment 8 at Week 12	17.451 percentage fat Standard Deviation 2.8338	14.817 percentage fat Standard Deviation 7.1945

SECONDARY outcome

Timeframe: 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)

Percent change from baseline in MRPDFF of liver segment 8 at baseline and at week 12 (Visit 8)

Outcome measures

Measure	Placebo n=9 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Percent Change From Baseline in Mean MRPDFF of Liver Segment 8	17.451 percentage change in MRPDFF Standard Deviation 8.6343	14.817 percentage change in MRPDFF Standard Deviation 7.1945

SECONDARY outcome

Timeframe: Baseline and Week 12 (Visit 8)

Population: Safety Population

Liver steatosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of decibels per meter (dB/M)

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Liver Steatosis Median Liver Steatosis Baseline	335 dB/M Interval 276.0 to 345.0	329 dB/M Interval 299.0 to 357.0
Liver Steatosis Median Liver Steatosis Week 12	345.0 dB/M Interval 320.0 to 360.0	329.0 dB/M Interval 279.0 to 351.0

SECONDARY outcome

Timeframe: 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)

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)

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Change in Liver Steatosis From Baseline	13.0 dB/M Interval 0.0 to 38.0	-16.0 dB/M Interval -38.0 to 22.0

SECONDARY outcome

Timeframe: 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)

Liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 Participants 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.
Liver Fibrosis Median Liver Fibrosis Baseline	8.4 kPa (kilo Pascals) Interval 6.4 to 9.0	8.6 kPa (kilo Pascals) Interval 6.7 to 9.2
Liver Fibrosis Median Liver Fibrosis Week 12	7.4 kPa (kilo Pascals) Interval 6.5 to 8.7	7.4 kPa (kilo Pascals) Interval 6.4 to 9.7

SECONDARY outcome

Timeframe: 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)

The change from baseline in liver fibrosis measured by FibroScan® at baseline and at week 12 (Visit 8), in units of kilo Pascals (kPa).

Outcome measures

Measure	Placebo n=11 Participants Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=19 Participants 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.
Change From Baseline of Liver Fibrosis	0.3 kPa (kilo Pascals) Interval -2.6 to 2.3	-0.8 kPa (kilo Pascals) Interval -2.5 to 3.8

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

ORMD-0801 (Insulin) Capsule 8 mg BD

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=11 participants at risk Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 participants at risk 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.
Cardiac disorders Atrial fibrillation	9.1% 1/11 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	0.00% 0/21 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Gastrointestinal disorders Gastrointenstinal hemorrhage	0.00% 0/11 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	4.8% 1/21 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03

Other adverse events

Measure	Placebo n=11 participants at risk Fish oil Placebo: Matching Placebo	ORMD-0801 (Insulin) Capsule 8 mg BD n=21 participants at risk 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.
Cardiac disorders Atrial Fibrillation	9.1% 1/11 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	4.8% 1/21 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Cardiac disorders Atrial Flutter	9.1% 1/11 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	0.00% 0/21 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Gastrointestinal disorders Addominal Distention	0.00% 0/11 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	23.8% 5/21 • Number of events 5 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Gastrointestinal disorders Nausea	0.00% 0/11 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	9.5% 2/21 • Number of events 2 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Infections and infestations COVID-19	9.1% 1/11 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	0.00% 0/21 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Metabolism and nutrition disorders Hyperglycemia	9.1% 1/11 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	0.00% 0/21 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/11 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03	4.8% 1/21 • Number of events 1 • Placebo Run-In (Week -2) through End-of-Study (Week 16); total of 18 weeks. NCI CTCAE v. 4.03

Additional Information

Chief Scientific Officer

Oramed, Ltd.

Phone: +97225660001

Email: miriam@oramed.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60