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

NCT06731075 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: ORA-D-013-3
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

ORA-013-3 is a randomized, controlled study to test the efficacy and safety of an oral capsule of ORMD-0801 at several doses in patients with Type 2 Diabetes Mellitus (T2DM) who have not responded well to other glucose-lowering medications. A total of three hundred subjects will be enrolled in this study and will be required to complete this thirty-four-week clinical trial.

Conditions

Type 2 Diabetes Mellitus

Keywords

Oral Insulin; Type 2 Diabetes Mellitus (T2DM)

Outcome Measures

Primary Outcomes (1)

• Change from baseline in A1C at 26 weeks

  Change from baseline (Visit 1) in A1C at 26 weeks (Visit 6).

  Visit 1 (baseline) and Visit 6 (week 26)

Secondary Outcomes (3)

• Incidence of A1C < 7% at 26 weeks (Visit 6).

  Week 26

• Change from baseline in fasting plasma glucose at week 26

  Baseline (Visit 1) to Week 26 (Visit 6)

• Safety Assessment by number of adverse events.

  Visit 1 (baseline) through Visit 6 (week 26)

Other Outcomes (13)

• Changes from baseline over time for A1C

  Measurements between Visit 1 (baseline) and Visit 6 (week 26)

• Changes from baseline over time for FPG

  Measurements between Visit 1 (baseline) and Visit 6 (week 26)

• Change of Mean Sensor Glucose,

  Baseline (Visit 1) to Week 26 (Visit 6)

Study Arms (4)

ORMD-0801 8 mg once-daily at night - QD

ACTIVE COMPARATOR

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).

Drug: ORMD-0801 8 mg; Other: Placebo capsule

ORMD-0801 8 mg twice daily - BID

ACTIVE COMPARATOR

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.

Drug: ORMD-0801 8 mg; Other: Placebo capsule

ORMD-0801 16 mg once-daily at night - QD

ACTIVE COMPARATOR

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.

Other: Placebo capsule; Drug: ORMD-0801 16 mg

Placebo

PLACEBO COMPARATOR

The subject receives 3 placebo capsules.

Other: Placebo capsule

Interventions

ORMD-0801 8 mg DRUG

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).

Also known as: Oral Insulin

ORMD-0801 8 mg once-daily at night - QD; ORMD-0801 8 mg twice daily - BID

Placebo capsule OTHER

Placebo capsule

ORMD-0801 16 mg once-daily at night - QD; ORMD-0801 8 mg once-daily at night - QD; ORMD-0801 8 mg twice daily - BID; Placebo

ORMD-0801 16 mg DRUG

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.

ORMD-0801 16 mg once-daily at night - QD

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged ≥ 50 years.
• Established diagnosis of T2DM for at least 6 months prior to Screening AND an A1C ≥ 7.2% but ≤ 10.0% at Screening.
• On a stable dose of at least one and up to three of the following glucose-lowering agents: Metformin, sulfonylurea, DPP-4 inhibitor, SGLT-2 inhibitor, thiazolidinedione, insulin secretagogue, oral or injected GLP-1 receptor agonists, glucosidase inhibitor, or pramlintide (injected insulin is excluded) for a minimum of 3 months prior to Screening.
• 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.
• Renal function - eGFR ≥ 30 ml/min.
• Females of childbearing potential must:
• \- a. Have a negative serum pregnancy test result at Screening.
• \- b. Agree to avoid becoming pregnant while receiving IP for at least 30 days prior to IP administration, during the entire study, and for 30 days following their last dose of IP.
• \- c. Agree to use an acceptable method of contraception at least 30 days prior to IP administration, during the entire study, and for 30 days following their last dose of IP. Acceptable methods of contraception are hormonal contraception (contraceptive pill or injection) PLUS an additional barrier method of contraception such as a diaphragm, condom, sponge, or spermicide.
• \- d. In the absence of hormonal contraception, double-barrier methods must be used which include a combination of any two of the following: diaphragm, condom, copper intrauterine device, sponge, or spermicide, and must be used for at least 30 days prior to administration of IP, during the entire study, and for 30 days following their last dose of IP.
• \- e. Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.
• \- f. Females who are not of childbearing potential are defined as:
• \- - - - - 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.

You may not qualify if:

• Type 1 diabetes by history.
• 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 injected insulin 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:
• \- - a. Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or \>1.5X the upper limit of normal; a single repeat test is allowable.
• \- - b. Elevated liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)) \> 3X the upper limit of normal; a single repeat test is allowable.
• \- - c. Very elevated fasting triglyceride levels (\> 600 mg/dL); a single repeat test is allowable.
• \- - d. Any relevant abnormality that would interfere with the efficacy or the safety assessments during study treatment administration.

Sponsors & Collaborators

• Oramed, Ltd.: lead
• InClin, Inc.: collaborator

Study Sites (1)

Velocity Clinical Research Dallas

Dallas, Texas, 75230, United States

Location

Related Publications (7)

• Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22.

  PMID: 18945920 BACKGROUND

• Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006 Aug;29(8):1963-72. doi: 10.2337/dc06-9912. No abstract available.

  PMID: 16873813 BACKGROUND

• Li X, Yang S, Cao C, Yan X, Zheng L, Zheng L, Da J, Tang X, Ji L, Yang X, Zhou Z. Validation of the Swedish Diabetes Re-Grouping Scheme in Adult-Onset Diabetes in China. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa524. doi: 10.1210/clinem/dgaa524.

  PMID: 32808015 BACKGROUND

• ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 3. Prevention or Delay of Type 2 Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S41-S48. doi: 10.2337/dc23-S003.

  PMID: 36507633 BACKGROUND

• Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.

  PMID: 8366922 BACKGROUND

• Cleary PA, Orchard TJ, Genuth S, Wong ND, Detrano R, Backlund JY, Zinman B, Jacobson A, Sun W, Lachin JM, Nathan DM; DCCT/EDIC Research Group. The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study. Diabetes. 2006 Dec;55(12):3556-65. doi: 10.2337/db06-0653.

  PMID: 17130504 BACKGROUND

• Mansour Aly D, Dwivedi OP, Prasad RB, Karajamaki A, Hjort R, Thangam M, Akerlund M, Mahajan A, Udler MS, Florez JC, McCarthy MI; Regeneron Genetics Center; Brosnan J, Melander O, Carlsson S, Hansson O, Tuomi T, Groop L, Ahlqvist E. Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes. Nat Genet. 2021 Nov;53(11):1534-1542. doi: 10.1038/s41588-021-00948-2. Epub 2021 Nov 4.

  PMID: 34737425 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ORMD-0801; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Miriam Kidron, Ph.D.

  Oramed, Ltd.

  STUDY DIRECTOR

Central Study Contacts

Miriam Kidron, Ph.D.

CONTACT

972-2-566-0001; miriam@oramed.com

Meir S. Silver, Ph.D.

CONTACT

+19706804074; meir@oramed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor, Contract Reserarch Organization and Medical Laboratories.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this randomized, double-blind, double dummy, placebo-controlled study, approximately 300 eligible subjects with T2DM and inadequate control on at least one to three glucose-lowering agents will undergo an initial 4-week Screening Period. This will be followed by a 26-week Double-Blind Treatment Period, commencing with a safety Follow-up Visit four weeks after the completion of the trial.

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 12, 2024
• Study Start: December 15, 2025
• Primary Completion (Estimated): April 25, 2027
• Study Completion (Estimated): May 22, 2027
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)