Clinical Trials

Date: 2014-04-24

Type of information: Results

phase: 2a

Announcement: results

Company: Oramed Pharmaceuticals (Israel)

Product: oral insulin ORMD-0801

Action mechanism:

Disease:

type 2 diabetes

Therapeutic area: Metabolic diseases

Country: USA

Trial details: Study ORA-D-009 was a single-center, randomized, double-blind, placebo-controlled, parallel group study that enrolled 30 patients with type 2 diabetes. It was designed as a sub-study, requested by the FDA prior to commencement of a large scale clinical trial with a similar design. At the time of enrollment, patients who enrolled were being treated by diet and exercise, or by diet, exercise and a stable dose of metformin for at least 6 weeks. Patients using metformin continued their treatment regimen throughout the study period. There was an initial outpatient, single-blind (patient blinded) placebo run-in period. Patients were then admitted to the clinical research center and received an additional dose of placebo, regardless of randomization, on the evening of Day 1 for the determination of baseline pharmacokinetic (PK) values. Prior to the first randomized treatment on the evening of Day 2, all patients were outfitted with a continuous glucose monitor (CGM). Patients were then randomized 1:1:1 to receive one of two doses of ORMD-0801 – 16 mg (two 8 mg gel capsules) or 24 mg (one 8 mg + one 16 mg dose capsule) – or matching placebo for the subsequent seven days, with a final PK evaluation performed on last day of treatment. Seven days after the end of the inpatient treatment period, patients returned to the study center for a follow-up visit and fasting blood draw. All 30 patients completed the study. The primary objective of this study was to evaluate the safety and tolerability of ORMD-0801. Secondary objectives were to evaluate the pharmacodynamic effects of ORMD?0801 on mean night time glucose, to evaluate the pharmacokinetics of ORMD-0801 and to evaluate changes from baseline in fasting blood (finger stick) and plasma glucose (FBG), morning fasting serum insulin, and C-peptide.

Latest news:

• • On April 24, 2014, Oramed Pharmaceuticals, a clinical-stage pharmaceutical company focused on the development of oral drug delivery systems, has announced detailed results from its previously completed Phase IIa trial investigating ORMD-0801, its orally ingestible insulin capsule, in type 2 diabetes patients. The results are being presented by Oramed's Chief Scientific Officer, Dr. Miriam Kidron, at the 2014 GTC Diabetes Summit, taking place in Cambridge, Massachusetts, USA. The trial was conducted in the United States under a FDA Investigational New Drug (IND) protocol. The results showed that ORMD-0801 oral insulin appeared to be safe and well-tolerated for the dosing regimen considered in this study. No hypoglycemic events occurred at any point in any treatment group and no treatment related adverse events were observed. Although the study was not powered to show statistical significance, there were trends observed showing pattern of well-defined and short-term increases in plasma insulin and decreases in blood glucose. While the study was ongoing, GMP analysis of study drug formulations revealed a formulation issue involving an excipient with the 16 mg gel caps that resulted in diminished and inconsistent release of study drug. This exclusively effected patients randomized to receive the 24 mg dose of ORMD-0801. The 8 mg capsules did not have this issue and demonstrated the correct release of medication. Patients in the 24 mg group were treated with one 8 mg gel cap and one 16 mg gel cap. The effective dose was, therefore, approximately one third of the intended dose. The formulation issue with the 16 mg gel caps has been investigated, identified and fully addressed.
• ORMD-0801 was safe and well tolerated. No patient experienced a hypoglycemic event at any point during the study and there were no serious or severe adverse events (AEs) nor any AEs related to the study drug. Three patients in the 16 mg group reported a total of five adverse events, four patients in the intended 24 mg group reported a total of five adverse events and five patients in the placebo group had a total of seven adverse events. None of these adverse events were assessed to be related to the study drug. The adverse events in the 16 mg group consisted of "Gastrointestinal disorders/Nausea," one patient (10%); and "Nervous system disorders/Headache," three patients (33.3%). There were no clinically significant changes in laboratory test results, vital signs, or physical examination.
• Continuous Glucose Monitoring (CGM) data were summarized for the following daily intervals: Nighttime (10 p.m. to 6 a.m.), Daytime (6 a.m. to 10 p.m.) and Fasting (5 a.m. to 7 a.m.). Nighttime CGM results showed a trend towards lower mean glucose for patients treated with 16 mg of ORMD-0801 compared with placebo. The overall mean difference for the seven days of treatment was -26.12 mg/dL, with a mean difference of -32.31 mg/dL during the last two days of data collection. Similar to nighttime results, daytime CGM analysis showed a trend towards lower levels of mean glucose for patients treated with 16 mg ORMD-0801 compared with placebo. The overall mean difference for the seven days of treatment was -23.44 mg/dL, with a mean difference of -22.83 mg/dL during the last two days of data collection. Fasting CGM analysis showed a trend towards lower levels of mean glucose for patients treated with 16 mg of ORMD-0801 compared with placebo. The overall mean difference for the seven days of treatment was -25.10 mg/dL, with a mean difference of -30.24 mg/dL during the last two days of data collection.
• Morning fasting blood glucose was additionally monitored each morning of the study by finger stick. On each of the mornings of Days 2 through 8, there was a trend toward lower mean finger stick blood glucose values for the 16 mg ORMD-0801 group than placebo. The greatest differences were -18.3 mg/dL and -18.2 mg/dL on Days 4 and 7, respectively.
• Mean C peptide levels decreased after an initial delay. By Day 9, the average decrease in C Peptide in the 16mg ORMD 0801 group compared to placebo was 0.293mg/dL after the delay (180-300 minutes post dose). In those patients treated with the intended 24 mg (8 mg + 16 mg gel capsules) ORMD-0801 dose, there were trends towards reduction in mean nighttime, mean daytime and mean fasting glucose levels, as measured with CGM. The differences versus placebo for these measurements were less pronounced than those observed in the 16 mg ORMD-0801 dose. As stated above, due to a study drug formulation issue affecting only the 10 patients randomized to receive 24 mg of ORMD-0801, the actual dose administered to these patients was likely closer to 8 mg.
• Morning fasting serum insulin was measured using a blood draw on the mornings of the screening visit, on Days 2 and 9 of the inpatient visit, and at the Day 16 follow-up visit. During the inpatient visit on the morning of Days 2 and 9, fasting morning serum insulin in the active treatment group was 2.92 ?IU/mL and 5.85 ?IU/mL higher than placebo, respectively.
• • On January 30, 2014, Oramed Pharmaceuticals has announced results from its Phase 2a clinical trial for its ORMD-0801 oral insulin capsule for the treatment of type 2 diabetes. The trial was conducted under a FDA IND (Investigational New Drug) protocol. The Phase 2a study met all primary and secondary endpoints. 30 patients with type 2 diabetes took part in the trial in an in-patient setting for one week.  Endpoints of safety as well as pharmacodynamic and pharmacokinetic effects were evaluated against a placebo control. Full results are expected to be presented at a scientific conference in the future. "Following on the results from this type 2 diabetes study we are gearing up to start a multi-center Phase 2b study later this year, stated Oramed CEO Nadav Kidron. We are also excited about the potential of this drug for type 1 diabetes and plan to initiate a Phase 2a FDA study for this indication in the near term."
• • On November 12, 2013, Oramed Pharmaceuticals has announced that the last patient has left the clinic from its U.S. FDA Phase 2a safety study for ORMD-0801. The Phase 2a trial, which enlisted 30 type 2 diabetes patients in an in-clinic setting for a seven-day period, was implemented in response to FDA feedback requesting a safety study on ORMD-0801 prior to initiating a larger multi-center trial in the US.
• • On July 8, 2013, Oramed Pharmaceuticals has announced that the first patient has been enrolled in a Phase 2a trial of ORMD-0801, an orally ingestible insulin capsule, on patients with type 2 diabetes. The current trial is to be a randomized, double-blind study designed to assess the safety of ORMD-0801.
• • On May 17, 2013, Oramed Pharmaceuticals has announced that theFDA has cleared the Company's IND for ORMD-0801, its oral insulin capsule.
• • On April 11, 2013, Oramed Pharmaceuticals has announced  that it has submitted a new Investigational New Drug (IND) application with the FDA for a sub-study on its oral insulin candidate, ORMD-0801. This filing is in response to FDA feedback from the initial IND filing on December 31, 2012, wherein the FDA requested Oramed to perform a sub-study in a controlled in-patient setting for up to a one-week period prior to beginning the larger multi-centered Phase 2 trial.
• • On February 14, 2013, Oramed Pharmaceuticals has announced that it has been in communication with the FDA regarding its IND application for oral insulin. The FDA has asked Oramed to perform a sub study in a controlled in-patient setting for up to a one-week period. In order to accommodate the FDA's request, Oramed will submit a new IND with a clinical protocol for the aforementioned sub study.
• • On January 7, 2013, Oramed Pharmaceuticals has announced  that it has filed an Investigational New Drug (IND) application with the FDA to begin a Phase 2 clinical trial of its orally ingested insulin candidate, ORMD-0801. The IND application was filed with the FDA on December 31, 2012. The trial is to include 147 type 2 diabetic patients in multiple centers across the United States. If Oramed does not receive comments from the FDA on the IND application within 30 days from filing, Oramed intends to immediately commence the trial to evaluate the safety, tolerability and efficacy of its oral insulin capsule on type 2 diabetic volunteers.
• • On March 23, 2011, Oramed Pharmaceuticals has announced that it has successfully completed a comprehensive toxicity study for its flagship oral insulin capsule, ORMD-0801. The study was completed under conditions prescribed by the FDA Good Laboratory Practices regulations and is the last study required to be performed before an Investigational New Drug (IND) filing. Three groups comprised of 30 rats each, were orally administered a once-daily, fixed-dose of one of three ORMD-0801 formulations for a period of 28 days. In parallel, three independent groups of identical sizes received various control formulations to ensure the safety of all applied exipients. Exipient doses in the assessed formulations were up to three times those used in ORMD-0801 capsules tested in clinical trials to date. Ten animals of each treatment group were monitored throughout an additional 14-day post-treatment recovery period. At the end of the respective monitoring periods, blood samples of all animals were measured for hematological, blood clotting, clinical chemistry and urinalaysis parameters, while ophthalmic, body and organ weight changes were also recorded. Food consumption and animal survival were followed throughout the study period. No mortality, adverse effects or changes in the evaluated parameters were observed throughout the treatment and recovery periods for any of the active or control test items.

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