Status and phase
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Treatments
About
To compare the efficacy of ORMD-0801 to placebo in improving glycemic control as assessed by A1C in inadequately controlled T2DM subjects on diet control alone or on diet control and metformin monotherapy or two or three oral glucose-lowering agents.
To assess the safety of repeat administration of ORMD-0801 in inadequately controlled T2DM subjects on on diet control alone or on diet control and metformin monotherapy or two or three oral glucose-lowering agents.
Full description
In this randomized, double-blind, double dummy, placebo-controlled study, approximately 608 eligible subjects with type 2 diabetes and inadequate control on diet control alone or on diet control and metformin monotherapy or on at least two and up to 3 oral glucose-lowering agents will undergo an initial 21-day Screening Period, followed by a 6 month Double-Blind Treatment Period and a 6 month Double-Blind Treatment Extension Period.
Screening Period:
The Investigator will review the aim of the study, study procedures and potential risks and benefits. These subjects will then sign a written informed consent during the Screening Visit 1. They will be scheduled to return to the clinic 10 days prior to randomization for Screening Visit 2. At this visit, a CGM sensor will be placed with appropriate instructions by the study team for a 10-day blinded continuous glucose monitoring (CGM) data collection by the site. Subjects will then return to the clinic after 10 days (± 1-day) for removal of the CGM sensor. The subjects will be randomized to one of the three arms of the study treatment.
6 month Double-Blind Treatment Period: After the Screening Period, subjects will be randomized to 6 months of the Double-Blind Treatment Period. In a double-blind, double dummy randomization scheme, subjects will either receive ORMD-0801 administered once-daily at night (1 x 8 mg capsule between 8 PM to 12 Midnight and no sooner than 1 hour after dinner) or ORMD-0801 8 mg (1 x 8 mg capsule) administered twice daily, each morning approximately 45 minutes (±15 minutes) prior to breakfast and each night prior to bedtime (between 8 PM to 12 Midnight and no sooner than 1 hour after dinner); or matching placebo. Subjects will receive 1 capsule approximately 45 minutes (±15 minutes) prior to breakfast and 1 capsule between 8 PM to 12 Midnight and no sooner than 1 hour after dinner.
During the Double-Blind Treatment Period commencing at Week 0 (Visit 1, CGM removal), subjects will return to the clinic every six weeks.
The visit requiring CGM application will occur 10 days prior to the CGM removal visit within ± 1-day window.
6-Month Double-Blind Treatment Extension Period: Following the completion of the Double-Blind Treatment Period, subject will enter a 6-month Double-Blind Treatment Extension Period. Subjects previously randomized to placebo during the Double-Blind Treatment Period will be randomized to receive either ORMD-0801 8 mg QD or 8 mg BID for the duration of the Double-Blind Treatment Extension Period. Subjects previously randomized to 8 mg QD or 8 mg BID during the Double-Blind Treatment Period will remain in the same treatment arm for the duration of the Double-Blind Treatment Extension Period. The Extension Period treatment assignments will remain blinded for the duration of the study.
Visits will occur at the following intervals during the 6-month Double-Blind Treatment: every six weeks. Extension Period: also every six weeks until the last visit (CGM removal and end of Double-Blind Treatment Extension Period visit).
The visit requiring CGM application will occur 10 days prior to the CGM removal visit within ± 1-day window.
All subjects completing the trial will return to the clinic in 2 weeks ± 3 days for a safety Follow-Up Visit. Subjects withdrawing prematurely from the trial will have the early termination (ET) visit procedures completed. All patients will continue to be followed in accordance with ITT principles to avoid lost to follow up and missing data.
Throughout the course of the study, subjects will measure and record fasting blood glucose levels at least 2-3 times a week [self-monitored blood glucose (SMBG)] or when they experience any symptoms of hypoglycemia using a glucose meter. Subjects will be provided a paper diary at each clinic visit and trained to record information related to fasting blood glucose and description of hypoglycemic events: time and date of occurrence; symptoms experienced, if any; treatment given, if any; and specific circumstances. Subjects will be required to bring the paper diary at each clinic visit where data will be reviewed.
Rescue Visits and Medication:
During both the Double-Blind Treatment Period and Double-Blind Treatment Extension Period, background oral glucose-lowering dose regimens will be maintained, and further dose adjustments are discouraged unless clinically indicated as follows:
Subjects will be eligible for rescue based on the following glycemic criteria:
Rescue will allow subjects to remain in the study, remain on double-blind study medication, complete all visits until the end of the study, and thereby, contribute to exposure and safety data. Rescue medication will be prescribed in accordance with the study Investigator's usual standard of practice.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Male and female subjects aged 18 - 75 years
Established diagnosis of T2DM for at least 6 months prior to Screening AND an A1C ≥ 7.5% but ≤ 11.0% at Screening
On a stable dose of at least two and up to three of the following oral glucose-lowering agents: Metformin, DPP-4 inhibitor, SGLT-2 inhibitor, thiazolidinedione, insulin secretagogue, or oral GLP-1 receptor agonists for a period of 3 months prior to Screening
Body mass index (BMI) of 25-40 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 ≥ 30 ml/min.
Females of childbearing potential must:
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.
Exclusion criteria
Subjects with:
Type 1 diabetes
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 < 0.4 ng/mL (0.13 nmol/L) at Screening
Diabetes attributable to other secondary causes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant).
Treatment involving glucosidase inhibitor, injected insulin, or injected GLP-1 receptor agonists (oral GLP-1 receptor antagonists are permitted), and pramlintide within 3 months prior to Visit 1.
A history of >2 episodes of severe hypoglycemia within 6 months prior to Screening.
A history of hypoglycemic unawareness.
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.
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
Renal dysfunction: eGFR < 30 mL/min
A history of or active proliferative retinopathy requiring treatment
Psychiatric disorders that, per Investigator judgment, may have impact on the safety of the subject or interfere with subject's participation or compliance in the study
Laboratory abnormalities at Screening including:
Positive history of active liver disease (other than non-alcoholic hepatic steatosis), primary biliary cirrhosis, or active symptomatic gallbladder disease
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)
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
Use of the following medications:
Known allergy to soy
Involvement in a weight loss program and is not in the maintenance phase, or subject has started weight loss medication (e.g., orlistat or liraglutide) within 3 months prior to Screening
Prior bariatric surgery
Subject is pregnant or breast-feeding
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
Any condition or other factor (at the Investigator's discretion) that is deemed unsuitable for subject enrollment into the study
Primary purpose
Allocation
Interventional model
Masking
608 participants in 3 patient groups
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Central trial contact
Dr. Dalal Alromaihi
Data sourced from clinicaltrials.gov
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