Phase 3 Study to Evaluate the Efficacy and Safety of ORMD-0801 in Subjects With Type 2 Diabetes Mellitus

Summary

Participation Requirements

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 ini...

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: From Day 1 (Visit 1) through Week 6 (Visit 2), if at least two fasting SMBG levels are > 270 mg/dL in the week preceding a visit are confirmed by a single central laboratory fasting glucose > 270 mg/dL. From Week 6 (Visit 2) through Week 12 (Visit 3), if at least two fasting SMBG levels are > 240 mg/dL in the week preceding a visit are confirmed by a single central laboratory fasting glucose > 240 mg/dL. From Week 12 (Visit 3) through Week 26 (Visit 6), if at least two fasting SMBG levels are > 220 mg/dL in the week preceding a visit are confirmed by a single central laboratory fasting glucose > 220 mg/dL. From Week 26 (Visit 6) through the end of the study, if at least two fasting SMBG levels are > 200 mg/dL in the week preceding a visit are confirmed by a single central laboratory fasting glucose > 200 mg/dL. 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.

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