ORMD-0801 for Diabetes

Overseen By Meir S. Silver, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Oramed, Ltd.

Must be taking: Glucose-lowering agents

Must not be taking: Injected insulin, Steroids

Disqualifiers: Type 1 diabetes, Severe hypertension, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral medication called ORMD-0801 to determine its effectiveness for people with Type 2 Diabetes (T2DM) who have not found success with other treatments. The study compares different doses of ORMD-0801 to a placebo, a pill without the active medication. The goal is to assess the safety and effectiveness of ORMD-0801 in controlling blood sugar levels. This trial may suit individuals who have had Type 2 Diabetes for at least 6 months, are on stable doses of certain diabetes medications, and still experience high blood sugar. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current glucose-lowering medications if you are on a stable dose of up to three specific types. However, if you are using injected insulin or certain other medications, you may need to stop those before joining the trial.

Is there any evidence suggesting that ORMD-0801 is likely to be safe for humans?

Research has shown that ORMD-0801 is generally safe for use. In various studies, participants tolerated ORMD-0801 well at doses of both 8 mg and 16 mg. For example, studies found that taking ORMD-0801 once or twice daily was safe and caused few unwanted side effects. One study demonstrated that ORMD-0801 lowered HbA1c, a measure of blood sugar levels, more effectively than a placebo, while maintaining safety. Additionally, trials with doses ranging from 8 to 48 mg reported no serious side effects. This suggests that ORMD-0801 is likely safe for participants, even at higher doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetes?

Researchers are excited about ORMD-0801 for diabetes because it offers a novel oral insulin delivery method. Unlike traditional insulin therapies, which typically require injections, ORMD-0801 is taken as a pill, making it potentially more convenient and less invasive for patients. This oral form of insulin may improve patient compliance and comfort, and it works by mimicking the natural path of insulin through the liver, which could offer better blood glucose regulation.

What evidence suggests that ORMD-0801 might be an effective treatment for Type 2 Diabetes?

Research shows that ORMD-0801, a pill form of insulin, may help treat Type 2 Diabetes. In this trial, participants may receive different dosages of ORMD-0801 or a placebo. Studies have found that ORMD-0801 lowers HbA1c levels, a key measure of blood sugar control, more effectively than a placebo. It is considered safe and well-tolerated by patients. Some research highlights its ability to lower blood sugar levels throughout the day, especially when taken at night. While some studies did not achieve their main goals, others have shown positive results, indicating potential benefits for people with uncontrolled diabetes. ^{2 3 6 7 8}

Who Is on the Research Team?

Miriam Kidron, Ph.D.

Principal Investigator

Oramed, Ltd.

Are You a Good Fit for This Trial?

This trial is for people with Type 2 Diabetes Mellitus who haven't had much success with other glucose-lowering meds. They'll be part of a study lasting about 34 weeks.

Inclusion Criteria

I have been on a stable dose of a diabetes medication for at least 3 months.

Body mass index (BMI) of ≤ 28 kg/m2 at Screening and stable weight, with no more than 5 kg gain or loss in the 3 months prior to Screening

My kidney function is good, with an eGFR of 30 ml/min or higher.

Exclusion Criteria

A history of > 2 episodes of severe hypoglycemia within 6 months prior to Screening

A history of hypoglycemic unawareness

My kidney function is low, with an eGFR under 30 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

3 visits (in-person)

Treatment

Participants receive double-blind treatment with ORMD-0801 or placebo for 26 weeks

26 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ORMD-0801

Trial Overview The study tests ORMD-0801, an oral capsule for diabetes, at two different doses (8 mg and 16 mg) compared to a placebo to see how effective and safe it is.

How Is the Trial Designed?

Group I: ORMD-0801 8 mg once-daily at night - QD Active Control 2 Interventions

Double-Dummy; the subject receives both experimental drug and placebo. 1 x 8 mg capsule between 8 PM to 12 Midnight and no sooner than 1 hour after dinner and 2 placebo capsules (1 in the morning and 1 at night).

Group II: ORMD-0801 8 mg twice daily - BID Active Control 2 Interventions

Double-Dummy; the subject receives both experimental drug and placebo. 1 x 8 mg capsule each morning approximately 45 minutes (±15 minutes) prior to breakfast and 1 x 8 mg capsule each night prior to bedtime (between 8 PM to 12 Midnight and no sooner than 1 hour after dinner) and 1 placebo capsule at night.

Group III: ORMD-0801 16 mg once-daily at night - QD Active Control 2 Interventions

Double-Dummy; the subject receives both experimental drug and placebo. 2 x 8 mg capsules between 8 PM to 12 Midnight and no sooner than 1 hour after dinner and 1 placebo capsule in the morning.

Group IV: Placebo Placebo Group 1 Intervention

The subject receives 3 placebo capsules.

Who Is Running the Clinical Trial?

Oramed, Ltd.

Lead Sponsor

Trials

15

Recruited

2,800+

InClin, Inc.

Collaborator

Trials

3

Recruited

620+

Published Research Related to This Trial

In a study of 69 patients with poorly controlled type 2 diabetes, improved control was significantly associated with better understanding of diabetes, adherence to meal plans, and regular glucose monitoring, highlighting the importance of self-care behaviors.

Interestingly, increased use of medications was inversely related to achieving better control, suggesting that patient education and lifestyle changes may be more effective than simply intensifying medication regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors that influence improvement for patients with poorly controlled type 2 diabetes. Hartz, A., Kent, S., James, P., et al.[2022]

In a study of 4627 patients with type 2 diabetes, those with moderate or poor glycemic control were significantly more likely to change their oral antidiabetic treatment patterns, such as switching or augmenting therapy, compared to those with good control.

Men generally had worse glycemic control at the start of treatment, and younger patients were more likely to modify their therapy, indicating that initial control levels and demographics play a crucial role in treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic control and the first use of oral antidiabetic agents among patients with type 2 diabetes mellitus. Mitchell, BD., Eby, EL., Lage, MJ.[2013]

In a study of type 2 diabetes patients with poor glycemic control despite insulin therapy, adding tofogliflozin significantly improved HbA1c levels, reducing them by -1.0% compared to a slight decrease in the insulin-only group.

Tofogliflozin not only helped lower HbA1c but also reduced the total daily insulin dose and weight in patients, indicating it may be a safe and effective add-on therapy for better diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Combined Tofogliflozin and Glargine, Tofogliflozin Added to Insulin, and Insulin Dose-Increase Therapy in Uncontrolled Type 2 Diabetes. Suzuki, K., Mitsuma, Y., Sato, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03467932

A Study to Evaluate the Efficacy and Safety of ORMD-0801 ... This is a four-way (Participant, Care Provider, Investigator, Outcomes Assessor) masked (blinded) study designed to explore the efficacy of ORMD-0801 when ...

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14901

Oral insulin (ORMD‐0801) in type 2 diabetes mellitus: A dose ... Oral insulin (ORMD-0801) induced greater reductions in HbA1c when compared to placebo, and was safe and well tolerated in individuals with uncontrolled T2DM.

3. oramed.com oramed.com/oramed-reports-positive-results-in-the-final-cohort-of-its-phase-2b-oral-insulin-trial/

Oramed Reports Positive Results in the Final Cohort of Its ... Patients randomized in the trial treated with 8 mg of ORMD-0801 once daily achieved an observed mean reduction of 1.29% from baseline and a least square mean ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34310011/

Efficacy and safety of 28-day treatment with oral insulin ... Conclusions: In patients with T2D, bedtime ORMD-0801 curbed increases in night-time glycaemia, 24-hour glycaemia and HbA1c, without increasing ...

5. oramed.com oramed.com/wp-content/uploads/2022/11/Final-Manuscript-Diabetes-Obesity-and-Metabolism-Nov.-2022.pdf

Oral Insulin (ORMD‐0801) in Type 2 Diabetes Mellitus Conclusions: Oral insulin (ORMD-0801) induced greater reductions in HbA1c when compared to placebo and was safe and well-tolerated in individuals with ...

6. oramed.com oramed.com/oramed-announces-additional-positive-safety-and-efficacy-data-from-its-phase-2-clinical-trial-of-ormd-0801-for-nash/

Oramed Announces Additional Positive Safety and Efficacy ... The trial demonstrated that ORMD-0801 was safe and well tolerated at 8 mg twice daily dosing, meeting the primary endpoint of no difference in adverse events ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35182035/

A Randomized, Double-Blind, Phase 1 Trial The results showed that the oral insulin formulations with either source in the dose range 8 to 48 mg were safe, and no serious adverse events ...

8. oramed.com oramed.com/wp-content/uploads/2022/06/007-CODHY-presentation.pdf

Efficacy and safety of ORMD-0801(Insulin Capsules) in the safety and efficacy of the addition of ORMD-0801 (16 mg insulin or 24 mg insulin) to metformin for 28 days in patients with T2DM. 7. Page 8. Completed ...