T2DM (Type 2 Diabetes Mellitus)
Conditions
Brief summary
This is a four-way (Participant, Care Provider, Investigator, Outcomes Assessor) masked (blinded) study designed to explore the efficacy of ORMD-0801 when given in different regimens across a dose range for up to 12 weeks in subjects with type 2 diabetes mellitus (T2DM).
Detailed description
This study is designed to explore the efficacy of ORMD-0801 when given in different regimens across a dose range for up to 12 weeks in subjects with type 2 diabetes mellitus (T2DM). There are two cohorts in this study. Approximately 360 subjects with T2DM will initially undergo a 2-week, single-blind placebo run-in period (Visits 1 and 2), followed by a 12-week treatment period (Visits 3 through 9). Cohort A will enroll 285 subjects; Cohort B will enroll 75 subjects For 265 of the 285 subjects of Cohort A, the total 12-week treatment period will include a Part 1dose escalation interval (2 weeks, Visits 3 and 4) and a Part 2 stable dose maintenance interval (10 weeks, Visits 5 through 9). In addition, per FDA request, the remaining 20 subjects (of the cohort total of 285 enrolled subjects) will receive excipient-matched placebo in a non-randomized single-blind fashion, TID (3 times per day), according to the same schedule as described above. For Cohort B (75 of the 360 total subjects), the total 12-week treatment period will include a stable dosing period for both Part 1 (2 weeks, Visits 3 and 4) and Part 2 (10 weeks, Visits 5 through 9). Cohort A data will be analyzed after Cohort A data collection has been completed (last subject for Cohort A screened on 7 May 2019). Estimated completion for Cohort A is October 2019. Cohort B data will be analyzed following the release of results from Cohort A.
Interventions
DRUGCohort A: ORMD-0801
Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2. Part 2: During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.
DRUGPlacebo oral capsule
Placebo provided QHS, BID, TID
DRUGCohort B: ORMD-0801
Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1. Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia.
Sponsors
Integrium
Oramed, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Single-Blind Placebo Run-in (Masking will be with Participant): During the placebo run-in period, subjects will self-administer blinded placebo study medication at night prior to bedtime (@10 PM ± 90 min. each night, no sooner than 2 hrs. after dinner). Outpatient glycemic levels and adverse events will be measured using self-monitored blood glucose (SMBG) and recorded in a diary. Treatment Period (Masking: Participant, Care Provider, Investigator, Outcomes Assessor) There are 2 Cohorts, A and B. Part 1 In the first 2 weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS (bedtime), BID (2 X / day) or TID. Part 2 Subjects will remain on fixed doses of ORMD-0801 or matched placebo for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. Treatment arms will consist of subjects receiving ORMD-0801 QHS, BID, and TID versus placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects aged 18 and older. * Established diagnosis of T2DM for at least 6 months prior to Screening, with an HbA1C (glycated hemoglobin) ≥ 7.5%. * Stable dose of metformin (at least 1500 mg or maximally tolerated dose)/oral antidiabetic (OAD) for a period of at least 3 months prior to screening. * Taking metformin only or metformin in addition to no more than two of the following: DPP-4 (DiPeptidyl Peptidase-4), SGLT-2 (Sodium-GLucose coTransporter-2), or TZD (Thiazolidinediones). * Body mass index (BMI) of up to 40 kg/m2 at Screening and stable weight, with no more than 5 kg gain or loss in the 3 months prior to Screening. * Renal function - eGFR (estimated glomerular filtration rate) \> 30 ml/min/1.73 m2 * Females of childbearing potential must have a negative serum pregnancy test result at Screening.
Exclusion criteria
* Subjects with insulin-dependent diabetes 1. has a history of type 1 diabetes mellitus or a history of ketoacidosis, or subject is assessed by the investigator as possibly having type 1 diabetes mellitus confirmed by a C-peptide \<0.7 ng/mL (0.23 nmol/L). 2. has a history of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant). * Treatment with glucosidase inhibitor, insulin secretagogues (other than sulfonylureas), glucagon-like peptide 1 (GLP-1) agonists within 3 months prior to Visit 1. * History of any basal, pre-mix or prandial insulin (greater than 7 days) within 6 months prior to Screening. * History of \>2 episodes of severe hypoglycemia within 6 months prior to Screening. * History of hypoglycemic unawareness (episodes of severe hypoglycemia with seizure or requiring third-party intervention or documented low blood glucose without associated autonomic symptoms) * Subjects with the following secondary complications of diabetes: 1. Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy/retinal photography examination performed (by a qualified person as per the country legislation) within 6 months prior to Screening. 2. Renal dysfunction: eGFR \< 30 ml/min/1.73 m2 3. History of proliferative retinopathy or severe form of neuropathy or cardiac autonomic neuropathy (CAN) 4. Uncontrolled or untreated severe hypertension defined as systolic blood pressure above or equal to 180 mmHg and/or diastolic blood pressure above or equal to 120 mmHg 5. Presence of unstable angina or myocardial infarction within 6 months prior to Screening, Grade 3 or 4 congestive heart failure (CHF) according to the New York Heart Association (NYHA) criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, cardiac surgery, history/occurrence of coronary angioplasty and/or stroke or transient ischemic attack (TIA) within 6 months prior to Screening. * Subjects with psychiatric disorders which, per investigator judgment may have an impact on the safety of the subject or interfere with the subject's participation or compliance in the study. * Subjects who needed (in the last 12 months) or may require systemic (oral, intravenous, intramuscular) glucocorticoid therapy for more than 2 weeks during the study period. * 9\. Laboratory abnormalities at Screening include: 1. C-peptide \< 1.0 ng/mL 2. Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or \>1.5X the upper limit of normal 3. Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) \>2X the upper limit of normal. 4. Very high triglyceride levels (\>600 mg/dL); a single repeat test is allowable. 5. Any relevant abnormality that would interfere with the efficacy or the safety assessments during the study treatment administration. * Positive history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease. * Positive history of HIV. * Use of the following medications: 1. History of any basal, pre-mix or prandial insulin (greater than 7 days) within 6 months prior to Screening. 2. Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening. 3. Administration of systemic long-acting corticosteroids within two months or prolonged use (more than one week) of other systemic corticosteroids or inhaled corticosteroids (if daily dosage is \> 1,000 μg equivalent beclomethasone) within 30 days prior to Screening. Intra-articular and/or topical corticosteroids are not considered systemic. 4. Use of medications known to modify glucose metabolism or to decrease the ability to recover from hypoglycemia such as oral, parenteral, and inhaled steroids (as discussed above), and immunosuppressive or immunomodulating agents. * Known allergy to soy. * Subject is on a weight loss program and is not in the maintenance phase or subject has started weight loss medication (e.g., orlistat or liraglutide), within 8 weeks prior to Screening. * Subject has had bariatric surgery. * Subject is pregnant or breastfeeding. * Subject is a user of recreational or illicit drugs or has had a recent history (within 1 year of Screening) of drug or alcohol abuse or dependence. (Note: Alcohol abuse includes heavy alcohol intake as defined by \>3 drinks per day or \>14 drinks per week, or binge drinking) at Screening. Occasional intermittent use of cannabinoid products will be allowed provided that no cannabinoid products have been used during the 1 week prior to each visit. * One or more contraindications to metformin as per local label. * History of gastrointestinal disorders (e.g. hypochlorhydria) with the potential to interfere with drug absorption. * At the Principal Investigator's discretion, any condition or other factors that are deemed unsuitable for subject enrollment into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of HbA1C (Glycated Hemoglobin) | baseline (Run-in period, Week 0, Visit 1) and Week 12 (follow-up) | Least Squares Means change in HbA1C from baseline to Week 12 of the treatment period, where HbA1C is reported in units of percent. The change in HbA1c from baseline to Week 12 is expressed as a change in the value of HbA1C. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline Over Time for HbA1C | Baseline (Run-In:Week 0, Visit 1) to Part 1, Visit 3, elapsed time: 3 weeks. | Mean change from baseline (Run-In, Week 0 Visit 1) to Part 1, Visit 3 for HbA1C (measured in mmols/mol) |
| Change Over Time in Hb1Ac | Baseline (week 0, visit 1) to Week 10, part 2 | Change of Hb1Ac from Baseline to Week 10, measured in mmol/mol |
Countries
United States
Participant flow
Recruitment details
Patients were recruited into two primary Cohorts, A and B. Cohort A: 1. ORMD-0801 1X daily 2. ORMD-0801 2X daily 3. ORMD-0801 3X daily 4. Matched Placebo Sub-Cohort A 20 subjects Per FDA, excipient matched placebo; randomized single-blind, TID, same schedule as for Cohort A. Not part of primary analysis. Cohort B: 1. ORMD-0801 8 mg 1X daily 2. ORMD-0801 8 mg 2X daily 3. ORMD-0801 16 mg 1X daily 4. ORMD-0801 16 mg 2X daily 5. Excipient matched placebo once daily
Pre-assignment details
After screening, patients underwent a 2-week, single-blind placebo run-in period (Visits 1\[baseline\] and 2), followed by a 12-week treatment period. Cohort A: 12-wk treatment period, 2 parts. Part 1, dose escalation interval for 2 weeks (Visits 3 and 4) Part 2, stable dose maintenance for 10 weeks (Visits 5-9). ; Cohort B: 12-wk treatment period, 2 parts. Part 1, stable dosing for 2 weeks (Visits 3 and 4) Part 2, stable dosing for 10 weeks, Visits 5-9).
Participants by arm
| Arm | Count |
|---|---|
| Cohort A+Cohort B Combined: Matched Oral Capsule Placebo Placebo matched to one of the three active comparator arms. (either QHS, BID, or TID)
Placebo oral capsule: Placebo provided QHS, BID, TID
This combined arm does not include the sub-cohort A, Excipient-Matched Placebo which per FDA is an exploratory endpoint, not part of the primary analysis. | 82 |
| Cohort A: ORMD-0801 Once Daily - QD Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Cohort A: ORMD-0801: Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2.
Part 2:
During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 69 |
| Cohort A: ORMD-0801 Twice Daily - BID Dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.
Cohort A: ORMD-0801: Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2.
Part 2:
During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 68 |
| Cohort A: ORMD-0801 Three Times Daily - TID ORMD-0801 three times daily - TID: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast and lunch.
Cohort A: ORMD-0801: Part 1 In the first two weeks of active treatment (Part 1) subjects will receive double-blind therapy according to their randomized regimen (placebo or ORMD-0801) to be taken QHS, BID or TID. Subjects will undergo a step-wise dose escalation from a starting dose of 16 mg (Visit 3), to 24 mg (Visit 4), to a top dose of 32 mg (Visit 5 onward). Subjects will then enter Part 2.
Part 2:
During Part 2, subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 69 |
| Cohort B:ORMD-0801, 8 mg Once Daily - QD ORMD-0801 8 mg once daily - QHS: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Cohort B: ORMD-0801: Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.
Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 15 |
| Cohort B: ORMD-0801 8 mg Twice Daily - BID ORMD-0801 8 mg twice daily - BID: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.
Cohort B: ORMD-0801: Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.
Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 17 |
| Cohort B: ORMD-0801 16 mg Once Daily - QD ORMD-0801 16 mg once daily - QHS: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes)
Cohort B: ORMD-0801: Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.
Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 18 |
| Cohort B: ORMD-0801 16 mg Twice Daily - BID ORMD-0801 16 mg twice daily - BID: dosed in the evening prior to bedtime (@ 10 PM ± 90 minutes) and 30-45 minutes prior to breakfast.
Cohort B: ORMD-0801: Part 1 In the first two weeks of active treatment, subjects will receive double-blind therapy according to their randomized regimen (ORMD 0801 8 mg or 16 mg, or matched placebo) to be taken QHS or BID. Subjects will then enter Part 2 at the same dose and regimen administered in Part 1.
Part 2 Subjects will remain on fixed doses of ORMD-0801 (or matched placebo) for 10 weeks. Doses will not be adjusted unless clinically indicated for adverse events or hypoglycemia. | 15 |
| Sub-Cohort A: Excipient Matched Placebo Data collected from participants who received excipient-matched placebo was an exploratory efficacy evaluation and therefore excluded from the primary and secondary analysis. | 20 |
| Total | 373 |
Baseline characteristics
| Characteristic | Cohort A: ORMD-0801 Once Daily - QD | Total | Sub-Cohort A: Excipient Matched Placebo | Cohort B: ORMD-0801 16 mg Twice Daily - BID | Cohort B: ORMD-0801 16 mg Once Daily - QD | Cohort B: ORMD-0801 8 mg Twice Daily - BID | Cohort B:ORMD-0801, 8 mg Once Daily - QD | Cohort A: ORMD-0801 Three Times Daily - TID | Cohort A+Cohort B Combined: Matched Oral Capsule Placebo | Cohort A: ORMD-0801 Twice Daily - BID |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.72 years STANDARD_DEVIATION 10.766 | 55.73 years STANDARD_DEVIATION 10.544 | 64.08 years STANDARD_DEVIATION 9.218 | 54.98 years STANDARD_DEVIATION 11.785 | 54.98 years STANDARD_DEVIATION 11.229 | 56.87 years STANDARD_DEVIATION 9.132 | 53.66 years STANDARD_DEVIATION 8.22 | 55.22 years STANDARD_DEVIATION 11.663 | 55.92 years STANDARD_DEVIATION 9.914 | 55.68 years STANDARD_DEVIATION 10.569 |
| BMI | 31.721 Kg/M^2 STANDARD_DEVIATION 4.9409 | 31.171 Kg/M^2 STANDARD_DEVIATION 4.7203 | 31.310 Kg/M^2 STANDARD_DEVIATION 5.5976 | 30.776 Kg/M^2 STANDARD_DEVIATION 5.453 | 31.881 Kg/M^2 STANDARD_DEVIATION 6.0514 | 31.005 Kg/M^2 STANDARD_DEVIATION 5.0333 | 31.759 Kg/M^2 STANDARD_DEVIATION 4.4393 | 31.191 Kg/M^2 STANDARD_DEVIATION 4.0045 | 31.137 Kg/M^2 STANDARD_DEVIATION 4.775 | 30.447 Kg/M^2 STANDARD_DEVIATION 4.771 |
| Diabetes Medications Metformin Alone | 20 Participants | 103 Participants | 6 Participants | 5 Participants | 7 Participants | 5 Participants | 6 Participants | 12 Participants | 22 Participants | 20 Participants |
| Diabetes Medications Metformin, No Sulfonylureas, but At Least 1 Other Medication | 10 Participants | 48 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 12 Participants | 13 Participants | 8 Participants |
| Diabetes Medications Metformin with Sulfonylureas and Other Medication(s) | 5 Participants | 40 Participants | 6 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants | 10 Participants | 8 Participants |
| Diabetes Medications Metformin with Sulfonylureas Only | 30 Participants | 151 Participants | 4 Participants | 3 Participants | 8 Participants | 7 Participants | 7 Participants | 33 Participants | 33 Participants | 26 Participants |
| Diabetes Medications Not on Metformin, But On 1 Other Medication | 4 Participants | 20 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 4 Participants | 3 Participants |
| Diabetes Medications Not on Metformin, But On At Least 2 Other Medications | 0 Participants | 11 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 191 Participants | 0 Participants | 8 Participants | 9 Participants | 8 Participants | 9 Participants | 36 Participants | 48 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 174 Participants | 20 Participants | 6 Participants | 9 Participants | 6 Participants | 6 Participants | 33 Participants | 33 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 8 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| HbA1c | 8.96 percent HbA1c STANDARD_DEVIATION 1.281 | 9.31 percent HbA1c STANDARD_DEVIATION 1.512 | 8.93 percent HbA1c STANDARD_DEVIATION 0.929 | 9.18 percent HbA1c STANDARD_DEVIATION 1.687 | 8.96 percent HbA1c STANDARD_DEVIATION 1.42 | 8.46 percent HbA1c STANDARD_DEVIATION 1.104 | 9.83 percent HbA1c STANDARD_DEVIATION 1.759 | 9.64 percent HbA1c STANDARD_DEVIATION 1.578 | 9.46 percent HbA1c STANDARD_DEVIATION 1.434 | 9.36 percent HbA1c STANDARD_DEVIATION 1.656 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 46 Participants | 3 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 8 Participants | 11 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 310 Participants | 17 Participants | 11 Participants | 16 Participants | 11 Participants | 12 Participants | 58 Participants | 69 Participants | 57 Participants |
| Sex: Female, Male Female | 27 Participants | 143 Participants | 8 Participants | 4 Participants | 7 Participants | 7 Participants | 5 Participants | 29 Participants | 33 Participants | 23 Participants |
| Sex: Female, Male Male | 42 Participants | 230 Participants | 12 Participants | 11 Participants | 11 Participants | 10 Participants | 10 Participants | 40 Participants | 49 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 69 | 0 / 68 | 0 / 69 | 0 / 15 | 0 / 17 | 0 / 18 | 0 / 15 | 1 / 20 |
| other Total, other adverse events | 11 / 82 | 19 / 69 | 6 / 68 | 10 / 69 | 5 / 15 | 2 / 17 | 1 / 18 | 2 / 15 | 13 / 20 |
| serious Total, serious adverse events | 0 / 82 | 5 / 69 | 0 / 68 | 3 / 69 | 0 / 15 | 0 / 17 | 0 / 18 | 1 / 15 | 3 / 20 |
Outcome results
Primary
Change From Baseline of HbA1C (Glycated Hemoglobin)
Least Squares Means change in HbA1C from baseline to Week 12 of the treatment period, where HbA1C is reported in units of percent. The change in HbA1c from baseline to Week 12 is expressed as a change in the value of HbA1C.
Time frame: baseline (Run-in period, Week 0, Visit 1) and Week 12 (follow-up)
Population: Data collected from participants who received excipient-matched placebo was an exploratory efficacy evaluation and therefore excluded from the primary and secondary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Cohort A +Cohort B: Matched-Placebo Oral Capsule | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.13 percent HbA1C |
| Cohort A: ORMD-0801 Once Daily - QHS | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.60 percent HbA1C |
| Cohort A: ORMD-0801 Twice Daily - BID | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.59 percent HbA1C |
| Cohort A: ORMD-0801 Three Times Daily - TID | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.51 percent HbA1C |
| Cohort B:ORMD-0801, 8 mg Once Daily - QHS: | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.95 percent HbA1C |
| Cohort B: ORMD-0801 8 mg Twice Daily - BID | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.95 percent HbA1C |
| Cohort B: ORMD-0801 16 mg Once Daily - QHS: | Change From Baseline of HbA1C (Glycated Hemoglobin) | 0.12 percent HbA1C |
| Cohort B: ORMD-0801 16 mg Twice Daily - BID | Change From Baseline of HbA1C (Glycated Hemoglobin) | -0.50 percent HbA1C |
Secondary
Change Over Time in Hb1Ac
Change of Hb1Ac from Baseline to Week 10, measured in mmol/mol
Time frame: Baseline (week 0, visit 1) to Week 10, part 2
Population: Intent-to-Treat; data collected from participants who received excipient-matched placebo was an exploratory efficacy evaluation and therefore excluded from the primary and secondary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Cohort A +Cohort B: Matched-Placebo Oral Capsule | Change Over Time in Hb1Ac | -1.27 mmol/mol |
| Cohort A: ORMD-0801 Once Daily - QHS | Change Over Time in Hb1Ac | -5.95 mmol/mol |
| Cohort A: ORMD-0801 Twice Daily - BID | Change Over Time in Hb1Ac | -4.95 mmol/mol |
| Cohort A: ORMD-0801 Three Times Daily - TID | Change Over Time in Hb1Ac | -6.16 mmol/mol |
| Cohort B:ORMD-0801, 8 mg Once Daily - QHS: | Change Over Time in Hb1Ac | -10.34 mmol/mol |
| Cohort B: ORMD-0801 8 mg Twice Daily - BID | Change Over Time in Hb1Ac | -10.71 mmol/mol |
| Cohort B: ORMD-0801 16 mg Once Daily - QHS: | Change Over Time in Hb1Ac | -0.25 mmol/mol |
| Cohort B: ORMD-0801 16 mg Twice Daily - BID | Change Over Time in Hb1Ac | -4.66 mmol/mol |
Secondary
Mean Change From Baseline Over Time for HbA1C
Mean change from baseline (Run-In, Week 0 Visit 1) to Part 1, Visit 3 for HbA1C (measured in mmols/mol)
Time frame: Baseline (Run-In:Week 0, Visit 1) to Part 1, Visit 3, elapsed time: 3 weeks.
Population: Intend-to-Treat; data collected from participants who received excipient-matched placebo was an exploratory efficacy evaluation and therefore excluded from the primary and secondary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Combined Cohort A +Cohort B: Matched-Placebo Oral Capsule | Mean Change From Baseline Over Time for HbA1C | -2.12 mmol/mol |
| Cohort A: ORMD-0801 Once Daily - QHS | Mean Change From Baseline Over Time for HbA1C | -2.56 mmol/mol |
| Cohort A: ORMD-0801 Twice Daily - BID | Mean Change From Baseline Over Time for HbA1C | -1.95 mmol/mol |
| Cohort A: ORMD-0801 Three Times Daily - TID | Mean Change From Baseline Over Time for HbA1C | -2.91 mmol/mol |
| Cohort B:ORMD-0801, 8 mg Once Daily - QHS: | Mean Change From Baseline Over Time for HbA1C | -3.26 mmol/mol |
| Cohort B: ORMD-0801 8 mg Twice Daily - BID | Mean Change From Baseline Over Time for HbA1C | -5.51 mmol/mol |
| Cohort B: ORMD-0801 16 mg Once Daily - QHS: | Mean Change From Baseline Over Time for HbA1C | -2.06 mmol/mol |
| Cohort B: ORMD-0801 16 mg Twice Daily - BID | Mean Change From Baseline Over Time for HbA1C | -1.87 mmol/mol |