Clinical trial NCT02496000: Phase II Safety and Efficacy Study of Oral ORMD-0801 in Patients With Type 2 Diabetes Mellitus
Official title: Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Multiple Oral Bedtime Doses of ORMD-0801 in Adult Patients With Type 2 Diabetes Mellitus Who Are Inadequately Controlled With Diet and Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Type 2
Keywords: Diabetes Mellitus type 2
Metformin
oral insulin
Lead sponsor: Oramed, Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Integrium
First posted: 2015-07-14
Enrollment: 188
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, double-blind, placebo-controlled, parallel group study.

Detailed description: This is a multicenter, Phase II, randomized, double-blind, placebo-controlled, parallel group study. After appropriate screening, approximately 180 male and female patients from up to 33 study centers will be treated in this study. Patients with type 2 diabetes mellitus who are being treated by diet, exercise, untreated with antidiabetic medications or treated with and metformin monotherapy or in combination with one other antidiabetic drug (excluding insulin) are eligible for enrollment.

Eligibility criteria: Inclusion Criteria:

* HbA1c ≥7.5% if naïve to antidiabetic therapy; ≥6.5% and ≤10% if on metformin ≥1,500 mg daily; ≥6.5% and ≤9.5% if on monotherapy with an antidiabetic drug other than metformin; ≥ 6.5% and ≤9.5% if on metformin and one other antidiabetic drug; ≥ 7.0% if on metformin \<1,500 mg daily.
* At time of randomization, patients will be treated for their diabetes by diet, exercise, and metformin (≥1500 mg/day; any type and regimen). Patients will have been on a stable regimen of metformin (defined as the same metformin dose and type) for at least two weeks prior to entering the single-blind placebo run-in period.
* Other antidiabetic agents will not be used for the two weeks prior to entering the placebo run-in period.
* Patients in whom the maximum tolerated dose (MTD) of metformin is 1,000 mg will be allowed to enter the study.
* At Day -7 (Visit 3), all patients will have HbA1c ≥ 6.5% and ≤10%.
* Body Mass Index between 25 and 40 kg/m2, inclusive.
* Fasting blood glucose ≥ 126 mg/dL (8.3 mmol/L) prior to randomization at Day -7 (Visit 3). For patients in whom the Day -7 (Visit 3) fasting blood glucose is \<126 mg/dL and ≥ 115 mg/dL, and the Day -7 (Visit 3) HbA1C is ≥ 7% and ≤ 10%, a minimum of 5 daily self- monitored fasting blood glucose checks recorded in the patient diary can be averaged. If the average value is ≥ 126 mg/dL, the patient may continue in the trial.
* Females of childbearing potential must have a negative urine pregnancy test result at screening. A negative urine pregnancy test must be obtained during Visit 2 and at Visit 4 (prior to randomization).
* Males and females of childbearing potential must use two methods of contraception (double barrier method), one of which must be an acceptable barrier method from the time of screening to the last study visit (Day 43).
* Patient has \>80% compliance with placebo during run in prior to randomization.
* Patient has ≥ 80% of the glucose readings on at least two 24 hour periods (6AM - 6AM) during the seven day CGM period.
* Patient has performed ≥ 10/14 of the self monitored glucose level measurements during placebo run-in, prior to randomization.

Exclusion Criteria:

- Patients who meet any of the following criteria are not eligible for this study.

* Presence of any clinically significant endocrine disease according to the Investigator (euthyroid patients on replacement therapy will be included if the dosage of thyroxine is stable for at least six weeks prior to Screening Visit).
* Clinical diagnosis of Type 1 diabetes.
* Fasting blood glucose \>260 mg/dL at the end of Day -7/Visit 3. For patient in whom the Day 07 (Visit 3) fasting blood glucose is \> 260 mg/dL and \< 300 mg/dL, and the Day -7 (Visit 3) HbA1C is ≥ 7% and ≤ 10%, a minimum of 5 self-monitored fasting blood glucose checks recorded in the patient diary can be averaged. If the average value is ≤ 260 mg/dL, the patient may continue in the trial.
* Presence or history of cancer within the past five years with the exception of adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer.
* Laboratory abnormalities at screening including:

  1. C-peptide \< 1.0 ng/mL.
  2. Positive pregnancy test in females of childbearing potential (at screening and start of run-in period).
  3. Abnormal serum thyrotropin (TSH) levels \>1.5 times the upper limit of normal.
  4. Positive test for hepatitis B surface antigen and/or hepatitis C antibody.
  5. Positive test for HIV.
  6. Serum Cr \>1.4mg/dl in males, \>1.3mg/dl in females.
  7. Any relevant abnormality interfering with the efficacy or the safety assessments during study drug administration.
* Use of the following medications:

  1. History of use of insulin for greater than one week in the last six months and any use of insulin in the last six weeks prior to randomization.
  2. Administration of anti-diabetic drugs other than metformin within four weeks prior to randomization visit. Administration of thyroid preparations or thyroxine within six weeks prior to screening visit. (Patients on stable thyroid replacement therapy for greater than 6 weeks may enter the study.)
* Administration of systemic long-acting corticosteroids within two months or prolonged use (more than one week) of other systemic corticosteroids or inhaled corticosteroids within 30 days prior to screening visit.
* Use of medications known to modify glucose metabolism or to decrease the ability to recover from hypoglycemia such as oral, parenteral, and inhaled steroids (as discussed above), beta blockers (with the exception of beta blocker ophthalmic solutions for glaucoma or ocular hypertension), and immunosuppressive or immunomodulating agents.
* History of tobacco or nicotine use in excess of two packs/day within ten weeks prior to screening.
* Patient is on a weight loss program and is not in the maintenance phase, or patient that started any approved or non approved weight loss medication within eight weeks prior to screening.
* Pregnancy or breast-feeding.
* Patient has a screening visit systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥100 mm Hg Patients will be allowed to take BP medication as long as they have been on a stable dose for a period of four weeks prior to the screening visit.
* Patient is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) 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).
* Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) greater than two times the upper limit of normal at screening.
* Very high triglyceride level (\>500 mg/dL) at screening.
* Any clinically significant electrocardiogram (ECG) abnormality at screening or cardiovascular disease. Clinically significant cardiovascular disease will include:

  1. History of stroke, transient ischemic attack, or myocardial infarction within six months prior to screening,
  2. History of or currently have New York Heart Associate Class II-IV heart failure prior to screening, or
  3. Uncontrolled hypertension defined as blood pressure ≥160 mmHg (systolic) or ≥100 mmHg (diastolic) at screening.

Primary outcomes:
measure: Measure of the Mean Night Time Glucose Levels Based on Two Nights of Glucose Measurements.
timeFrame: Baseline-Study day -7 (± 1 day) through Study day 1 (± 1 day), and Week 4 -Study day 22 (± 1 day) through Study day 29 (± 1 day)
Secondary outcomes:
measure: The Effect of ORMD-0801 on Mean 24-hour Glucose
timeFrame: Study day -7 (± 1 day) through Study day 1 (± 1 day), and Study day 22 (±1 day) - Study day 29 (± 1 day)
measure: Measure Percent Change in Continuous Glucose Monitoring Mean Fasting Glucose Between Treatment and Run-In
timeFrame: Baseline (Run-in days 13-14) and Study day 1 (± 1 day) through Study day 29 (± 1 day)
measure: Measure the Change From Baseline to End of the Study of Morning Fasting C-Peptide (Nmol/L)
timeFrame: Study day 1 (±1 day) through Study day43 (± 1 day)
measure: The Effect of ORMD-0801 on the Percent Change in HbA1c
timeFrame: Study day 1 (± 1 day) through Study day 29 (± 1 day)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Steingard Medical Group
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic, PA
state: Arkansas
city: Anaheim
country: United States
facility: Dream Team Clinical Research
state: California
city: Los Angeles
country: United States
facility: ACTCA, Inc.
state: California
city: Los Angeles
country: United States
facility: ACTCA
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: San Mateo
country: United States
facility: Mills-Peninsula Health Services
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates, PC
state: Colorado
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Hialeah
country: United States
facility: Research in Miami Inc.
state: Florida
city: Hialeah
country: United States
facility: Research in Miami, Inc.
state: Florida
city: Miami
country: United States
facility: Phoenix Medical Research LLC
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Medical Arts Pharmaceutical Research Center
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc
state: Florida
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Auburn
country: United States
facility: Maine Research Associates
state: Maine
city: Flint
country: United States
facility: Apex Medical Research, MI, Inc
state: Michigan
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: New York
country: United States
facility: New York Clinical Trials
state: New York
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Greenville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Corpus Christi
country: United States
facility: Padre Coast Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: San Antonio
country: United States
facility: Southwest Clinic
state: Texas
city: San Antonio
country: United States
facility: Panacea Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc.
state: Washington
Study officials:
affiliation: Orange County Research Center
name: Joel M Neutel, M.D.
role: PRINCIPAL_INVESTIGATOR
References: