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

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ClinicalTrials.gov Identifier: NCT04606576
Recruitment Status : Recruiting
First Posted : October 28, 2020
Last Update Posted : January 7, 2021
Sponsor:
Collaborator:
Integrium
Information provided by (Responsible Party):
Oramed, Ltd.

Tracking Information
First Submitted Date  ICMJE October 22, 2020
First Posted Date  ICMJE October 28, 2020
Last Update Posted Date January 7, 2021
Actual Study Start Date  ICMJE November 23, 2020
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2020)
Mean change from baseline in A1C [ Time Frame: Baseline and 26 Weeks ]
The mean change from baseline (Visit 1) in A1C at 26 weeks (Visit 6) for the active and placebo groups.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2020)
Mean change in fasting glucose [ Time Frame: Baseline and 26 weeks ]
The Mean change from baseline (Visit 1) in fasting plasma glucose at 26 weeks (Visit 6) will be analyzed using a linear mixed model similar to the primary analysis.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Efficacy and Safety of ORMD-0801 in Subjects With Type 2 Diabetes Mellitus
Official Title  ICMJE A Double-Blinded, Placebo-controlled, Double Dummy, Multi-center Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of ORMD-0801 in Subjects With T2DM With Inadequate Glycemic Control on 1, 2 or 3 Oral Glucose-lowering Agents.
Brief Summary In this randomized, double-blind, double-dummy, placebo-controlled study, approximately 675 eligible subjects with type 2 diabetes and inadequate control on at least one and up to 3 oral glucose-lowering agents will undergo an initial 21-day Screening Period, followed by a 26-week Double-Blind Treatment Period and a 26-week Double-Blind Treatment Extension Period.
Detailed Description

Screening Period Subjects will provide a written informed consent during 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 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.

3.1.2 26-Week Double-Blind Treatment Period After the Screening Period, subjects will be randomized to 26 weeks 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 at the following intervals: Week 6 - Visit 2; Week 12 - Visit 3; Week 18 -Visit 4; Week 24 - Visit 5 (10 days (± 1-day) prior to Week 26 for CGM application) and Week 26 - Visit 6 (CGM removal and end of Double-Blind Treatment Period visit).

The visit requiring CGM application will occur 10 days prior to the CGM removal visit within ± 1-day window.

3.1.3 26-Week Double-Blind Treatment Extension Period Following the completion of the Double-Blind Treatment Period, subject will enter a 26-week 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
In this randomized, double-blind, double dummy, placebo-controlled study, approximately 675 eligible subjects with type 2 diabetes and inadequate control on at least one and up to 3 oral glucose-lowering agents will undergo an initial 21-day Screening Period, followed by a 26-week Double-Blind Treatment Period and a 26-week Double-Blind Treatment Extension Period.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Other: Placebo
    Fish Oil
    Other Name: Fish Oil
  • Drug: ORMD-0801 QD
    Oral Insulin once per day
    Other Name: Oral Insulin
  • Drug: ORMD-0801 BD
    Oral Insulin, twice per day
    Other Name: Oral Insulin
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Fish Oil
    Intervention: Other: Placebo
  • Experimental: ORMD-0801 QD
    8 mg ORMD-0801 administered QD at night
    Intervention: Drug: ORMD-0801 QD
  • Experimental: ORMD-0801 BID
    8 mg ORMD-0801 administered at night and in the morning 45 minutes before breakfast.
    Intervention: Drug: ORMD-0801 BD
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2020)
675
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female subjects aged 18 - 75 years.
  • Established diagnosis of T2DM for at least 6 months prior to Screening AND an A1C ≥ 7.5% but ≤ 11.0% at Screening.
  • On a stable dose of at least one and up to three of the following oral glucose-lowering agents: Metformin, DPP-4 inhibitor, SGLT-2 inhibitor, thiazolidinedione, or sulfonylurea for a period of 3 months prior to Screening.
  • Body mass index (BMI) of 25-40 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 - GFR ≥ 30 ml/min/1.73 m2.
  • 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.

Exclusion Criteria:

Subjects with:

  • Type 1 diabetes.
  • A history of diabetes mellitus with ketoacidosis or is assessed by the Investigator as possibly having type 1 diabetes mellitus confirmed by a C-peptide < 0.4 ng/mL (0.13 nmol/L) at Screening.
  • 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 glucosidase inhibitor, insulin secretagogues (other than sulfonylureas), or GLP-1 receptor agonists 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: GFR < 30 mL/min/1.73 m2.
  • Active proliferative retinopathy requiring treatment.
  • Psychiatric disorders that, per Investigator judgment, may have impact on the safety of the subject or interfere with the subject's participation or compliance in the study.
  • Laboratory abnormalities at Screening including:

    • a. C-peptide < 0.4 ng/mL.
    • b. 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.
    • c. Elevated liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)) >3X the upper limit of normal; a single repeat test is allowable.
    • d. Very high fasting triglyceride levels (>600 mg/dL); a single repeat test is allowable.
    • e. Any relevant abnormality that would interfere with the efficacy or the safety assessments during study treatment administration.
  • Positive history of active liver disease (other than non-alcoholic hepatic steatosis), primary biliary cirrhosis, or active symptomatic gallbladder disease.
  • Positive results for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus ribonucleic acid (RNA).
  • Patient has active or history of neoplastic disease (except for adequately treated non-invasive basal cell and/or squamous cell carcinoma or carcinoma in situ of the cervix) within the past 5 years prior to Baseline.
  • Use of the following medications:

    • a. History of use of any injectable or inhaled, basal, pre-mixed or prandial insulin (greater than 7 days) within 6 months prior to Screening.
    • b. Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening.
    • c. Requirements (in the last 12 months), or may require, systemic (oral, intravenous, intramuscular) glucocorticoid therapy for more than 2 weeks during the study period. Intra-articular and/or topical corticosteroids are not considered systemic.
    • d. Use of medications known to modify glucose metabolism or to decrease the ability to recover from hypoglycemia such as oral, parenteral, and immunosuppressive or immunomodulating agents. Inhaled nasal steroids are permissible.
  • Known allergy to soy.
  • Involvement in a weight loss program and is not in the maintenance phase, or subject has started weight loss medication (e.g., orlistat or liraglutide) within 3 months prior to Screening.
  • Prior bariatric surgery.
  • Subject is pregnant or breast-feeding.
  • Subject is a user of recreational or illicit drugs or has had a recent history (within 1 year of Screening) of drug or alcohol abuse or dependence. (Note: Alcohol abuse includes heavy alcohol intake as defined by >3 drinks per day or >14 drinks per week or binge drinking) at Screening. Occasional intermittent use of cannabinoid products will be allowed provided that no cannabinoid products have been used during the 1 week prior to each visit.
  • Contraindications to metformin use as per label.
  • A history of gastrointestinal disorders (e.g. hypochlorhydria) with the potential to interfere with drug absorption.
  • Any condition or other factor (at the Investigator's discretion) that is deemed unsuitable for subject enrollment into the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kim Pope, RN, BSN 830-438-7162 Kim.Pope@integrium.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04606576
Other Study ID Numbers  ICMJE ORA-D-013-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Oramed, Ltd.
Study Sponsor  ICMJE Oramed, Ltd.
Collaborators  ICMJE Integrium
Investigators  ICMJE
Study Director: Miriam Kidron, PhD Oramed, Ltd.
PRS Account Oramed, Ltd.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP