In a randomized, double-blind, placebo-controlled phase IIa study, researchers assessed the safety and tolerability of ORMD-0801. Secondary objectives included an evaluation of pharmacodynamics on mean night time glucose and pharmacokinetics. Researchers further evaluated the changes in fasting blood glucose, morning fasting insulin levels and C-peptide levels.
Thirty patients with type 2 diabetes were assigned to receive either 16 mg or 24 mg of insulin or placebo at bedtime over the course of 8 days. These patients were concurrently treated with either diet or exercise alone or in conjunction with a stable dose of metformin for at least 6 weeks. Study participants using metformin were continued on it for the duration of the study.
A formulary issue involving an excipient found only in the 16mg gel tabs became apparent during the study, which ultimately resulted in inconsistent release of drug from the dosage form. This affected individuals randomized to receive a 24 mg dose. To account for this problem, patients in the 24 mg group were given with one 8 mg gel cap and one 16 mg gel cap, however the effective dose was, approximated at being 1/3 of the intended dose.
In study participants, ORMD-0801 was found to be both safe and well tolerated. No study participants experienced any hypoglycemic events at any point throughout the study and no severe adverse events occurred. Minor adverse events were limited to gastrointestinal disorders/nausea and nervous system disorders/headache. In those receiving 16 mg, 5 patients reported a minor adverse event in the 16 mg group reported a total of 5 adverse events. In the 24 mg group, 4 patients reported a total of 5 adverse events and in the placebo group and 5 patients reported a total of 7 adverse events. None of these adverse events were determined to be related to the study drug and no clinically significant changes were found in laboratory values, vitals, or during physical examination.
In study participants receiving 16 mg of ORMD-0801, favorable trends were observed.
The average difference of night time continuous glucose monitoring was -26.12 mg/dL after the 7 day course, with a mean difference of -32.31 mg/dL observed during the final 48 hours.
Daytime continuous glucose monitoring showed a favorable trend towards lower levels of mean glucose in those treated with a 16 mg dose of ORMD-0801 compared to placebo – with an overall average mean difference of -23.44 mg/dL and a mean difference of -22.83 mg/dL during the final 2 days.
An analysis of fasting continuous glucose monitoring revealed lower levels of mean glucose for patients with an overall average difference over the 7 days of -25.10 mg/dL and an average difference of -30.24 mg/dL during the final 2 days. Further, morning fasting blood glucose showed a trend in favor of 16 mg ORMD-0801 compared to placebo, with the largest differences being -18.3 mg/dL on day 4 and -18.2 mg/dL on day 7.
In the 16 mg ORMD-0801 group a decrease in C-peptide levels was noted. On day 9, the mean decrease in C-Peptide in compared to placebo was 0.293mg/dL.
In study participants treated with 24 mg of ORMD-0801, researchers found reductions in the mean nighttime, daytime and fasting glucose levels – with differences less pronounced in placebo compared to those receiving 16 mg of ORMD-0801.
- ORMD-0801 is an oral formulation of insulin which appears to be safe and well-tolerated in this small, short-term clinical trial
- An oral form of insulin may result in better patient compliance and ultimately result in better glycemic control
- Further, large, appropriately-powered studies are needed assess the efficacy as well as the safety and tolerability of ORMD-0801 in the long-term
1. http://pipelinereview.com/index.php/2014042554062/Proteins-and-Peptides/Oramed-Pharmaceuticals-Presents-Data-from-Phase-IIa-Trial-with-ORMD-0801-in-Type 2-Diabetes-at-the-2014-Diabetes-Summit.html