Type 2 Diabetes Mellitus (T2DM) MedDRA version: 21.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 21.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Code: ORMD-0801
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ORMD-0801
Current Sponsor code: ORA-D-013-2
Other descriptive name: INSULIN HR1799
Concentration unit: mg milligram(s)
Sponsors
Oramed Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged, 18 to 75 years. 2. Established diagnosis of T2DM prior to Screening AND an A1C = 7.0% but = 9.0% at Screening. 3. Subjects should be on: a. Diet and exercise therapy and have never been treated with any oral or injectable glucose-lowering therapy, determined at Screening; OR b. Diet and exercise therapy with no oral or injectable glucose-lowering therapy for a period of at least 3 months prior to Screening; OR c. Diet and exercise therapy with a stable glucose-lowering agent as monotherapyfor a period of at least 3 months prior to Screening. 4. Body mass index (BMI) of 25-40 kg/m2at Screening and stable weight, with no more than 5 kg gain or loss in the 3 months prior to Screening. 5. Renal function – eGFR = 30 ml/min. 6. Females of childbearing potential must: a. have a negative serum pregnancy test result at Screening. b. agree to avoid becoming pregnant while receiving IP for at least 30 days prior to IP administration, during the entire study, and for 30 days following their last dose of IP. c. agree to use an acceptable method of contraception at least 30 days prior to IP administration, during the entire study, and for 30 days following their last dose of IP. Acceptable methods of contraception are hormonal contraception (contraceptive pill or injection) PLUS an additional barrier method of contraception such as a diaphragm, condom, sponge, or spermicide. d. In the absence of hormonal contraception, double-barrier methods must be used which include a combination of any two of the following: diaphragm, condom, copper intrauterine device, sponge, or spermicide, and must be used for at least 30 days prior to administration of IP, during the entire study, and for 30 days following their last dose of IP. e. Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject’s preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception. f. Females who are not of childbearing potential are defined as: i. Postmenopausal (defined as at least 12 months with no menses in women =45 years of age); OR ii. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR iii. Have a congenital or acquired condition that prevents childbearing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 383 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 67
Exclusion criteria
Exclusion criteria: 1. Type 1 diabetes. 2. A history of diabetes mellitus with ketoacidosis or is assessed by the Investigator as possibly having type 1 diabetes mellitus confirmed by a C-peptide 2 episodes of severe hypoglycemia within 6 months prior to Screening. 6. A history of hypoglycemic unawareness. 7. A history of unstable angina or myocardial infarction within 6 months prior to Screening, New York Heart Association (NYHA) Grade 3 or 4 congestive heart failure (CHF), valvular heart disease, ventricular cardiac arrhythmia requiring treatment, pulmonary hypertension, cardiac surgery, coronary angioplasty, stroke or transient ischemic attack (TIA) within 6 months prior to Screening. 8. A history of uncontrolled or untreated severe hypertension defined as systolic blood pressure above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg. A single repeat measurement will be permitted. 9. Renal dysfunction: eGFR 1.5X the upper limit of normal; a single repeat test is allowable. c. Elevated liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)) >3X the upper limit of normal; a single repeat test is allowable. d. Very elevated fasting triglyceride levels (>600 mg/dL); a single repeat test is allowable. e. Any relevant abnormality that would interfere with the efficacy or the safety assessments during study treatment administration. 13. Positive history of active liver disease (other than non- alcoholic hepatic steatosis), primary biliary cirrhosis, or active symptomatic gallbladder disease. 14. Positive results for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus ribonucleic acid (RNA). 15. Patient has active or history of neoplastic disease (except for adequately treated non-invasive basal cell and/or squamous cell carcinoma or carcinoma in situ of the cervix) within the past 5 years prior to baseline. 16. Use of the following medications: a. History of use of any injectable or inhaled, basal, pre- mixed or prandial insulin (greater than 7 days) within 6 months prior to Screening. b. Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening. c. Requirements (in the last 12 months), or may require, systemic (oral, intravenous, intramuscular) glucocorticoid therapy for more than 2 weeks during the study period. I
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ORMD-0801 compared to placebo in improving glycemic control as assessed by A1C in inadequately controlled T2DM subjects on diet control alone or on diet control and glucose-lowering agents as monotherapy over a 26-week treatment period.;Secondary Objective: • To examine the efficacy of ORMD-0801 compared to placebo in maintaining glycemic control over a 52-week treatment period. • To compare the safety of ORMD-0801 treatment compared to placebo in inadequately controlled T2DM subjects on diet control alone or on diet control and glucose-lowering agents as monotherapy.;Primary end point(s): Change from baseline (Visit 1) in A1C at 26 weeks (Visit 6).;Timepoint(s) of evaluation of this end point: 26 weeks (Visit 6) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: 1. Change from baseline (Visit 1) in fasting plasma glucose at 26 weeks (Visit 6). 2. Incidence of A1C 250 mg/dL. • Incidence of A1C < 8% at 26 weeks (Visit 6), and at 52 weeks (Visit 10). • Incidence of A1C < 7% at 52 weeks (Visit 10) without reported severe hypoglycemic events. • Incidence rate of subjects requiring glycemic rescue therapy and the time to rescue during the Double-Blind Treatment Period and the Double-Blind Treatment Extension Period. • Change in weight from baseline during the Double-Blind Treatment Period and the Double-Blind Treatment Extension Period. • Changes from baseline over time for C-peptide and HOMA during the Double-Blind Treatment Period and the Double-Blind Treatment Extension Period.;Timepoint(s) of evaluation of this end point: Primary Endpoint: 26 weeks (Visit 6) Secondary Efficacy Endpoints: 26 weeks (Visit 6) Secondary Safety Endpoint: Based on adverse event reporting Exploratory endpoints: 1. from baseline (Visit 1) during the Double- Blind Treatment Period and the Double-Blind Treatment Extension Period. 2. from baseline (Visit 1) at weeks 26 and 52. 3. at 26 weeks (Visit 6), and at 52 weeks (Visit 10). 4. at 52 weeks (Visit 10) 5. during the Double- Blind Treatment Period and the Double-Blind Treatment Extension Period. 6. during the Double- Blind Treatment Period and the Double-Blind Treatment Extension Period. 7. during the Double- Blind Treatment Period and the Double-Blind Treatment Extension Period. | — |
Countries
Germany, Hungary, Israel, Italy, Spain, United Kingdom
Contacts
Public ContactBarbara Hevesi-Tóth
Precision for Medicine
Outcome results
None listed