Type 2 Diabetes MellitusPhase 2NCT02954601
A Study of Single and Multiple Doses of Oral Insulin or Placebo in Subjects With Type 2 Diabetes Mellitus
A Phase 2 study testing ORMD-0801 (qd), ORMD-0801 (bid) and ORMD-0801 (tid) in people with Type 2 Diabetes Mellitus, run by Oramed, Ltd. at 1 site in United States.
Trial summary
This is a four-way crossover (non-parallel) study with each subject receiving three of the four arms. The study will enroll approximately 30 adult subjects with T2DM from age 20 to 75 inclusive. Following a 7-10 day Screening period, eligible subjects will enter a 3-day single-blind placebo run-in. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- ORMD-0801 (qd), ORMD-0801 (bid) and ORMD-0801 (tid)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to 15 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects, age 20 to 75 years, inclusive with type 2 diabetes mellitus.
- At Visit 2/Period 1/Day 1, subjects will have been treated for their diabetes by metformin (≥1000 mg/day; any type and regimen), metformin and a DPP-4 inhibitor ( Dipeptidyl-Peptidase)-4), metformin and an SGLT-2 (Sodium-glucose co-transporter 2) inhibitor, metformin and TZD (Thiazolidinediones), or metformin and sulfonylurea. Subjects will have been on a stable regimen of metformin (defined as the same metformin dose and type) and other treatments for at least 8 weeks prior to Visit 2/Period 1/Day 1.
- Body Mass Index (BMI) between 25 and 40 kg/m2, inclusive, at Screening.
- Hemoglobin A1c (HbA1c) between ≥7.5 and ≤10.5% at Screening.
- Fasting serum glucose greater than or equal to 126 mg/dL at Screening.
- Females of childbearing potential must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test at Visit 2/Day 1 for all study Periods.
Show all 10Show fewer
- Females who are not of childbearing potential are defined as:
- Postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age) ii. Has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR iii. Has a congenital or acquired condition that prevents childbearing.
- Females of childbearing potential agree to avoid becoming pregnant while receiving study treatment and for 14 days after the last dose of study treatment by complying with one of the following:
- practice abstinence† from heterosexual activity OR ii. Use (or have her partner use) acceptable contraception during heterosexual activity.
Who cannot join
- Usage of anti-diabetic agents other than metformin, sulfonylurea, SGLT-2 inhibitors, TZD, or DPP-4 inhibitors within 6 weeks prior to Visit 2/Period 1/Day 1.
- Presence of any clinically significant endocrine disease according to the Investigator (euthyroid subjects on replacement therapy will be included if the dosage of thyroxine is stable for at least six weeks prior to Screening).
- Clinical diagnosis of type 1 diabetes.
- Fasting serum glucose >300 mg/dL at Screening; a single repeat test is allowable.
- Evidence of unawareness of hypoglycemia, a documented plasma glucose ≤50 mg/dL in the absence of symptoms of hypoglycemia at Screening.
- Presence of any clinically significant condition (in the opinion of the Investigator) that might interfere with the evaluation of study medication, such as significant renal, hepatic, gastrointestinal (GI), cardiovascular (CV), immune disease, blood dyscrasias or any disorders causing hemolysis or unstable red blood cells, or clinically important hematological disorders (i.e. aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) at Screening.
Show all 33Show fewer
- Presence or history of cancer within the past 5 years of Screening, with the exception of adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer.
- A subject with a history of malignancy >5 years prior to Screening should have no evidence of residual or recurrent disease.
- A subject with a history of melanoma, leukemia, lymphoma, or renal carcinoma is excluded.
- Laboratory abnormalities at Screening including:
- C-peptide < 1.0 ng/mL;
- Positive pregnancy test in females of childbearing potential (at Screening and Visit 2/Periods 1-3/Day 1);
- Abnormal serum thyrotropin (TSH) levels below the lower limit of normal or >1.5X (1.5 times) the upper limit of normal
- Elevated liver enzymes (alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase) >2X the upper limit of normal.
- Very high triglyceride levels (>600 mg/dL); a single repeat test is allowable.
- 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), including chronic hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease.
- Positive history of HIV.
- Use of the following medications:
- History of use of insulin for more than 1 week within 6 months prior to and none within 6 weeks prior to Visit 2/Period 1/Day 1.
- History of use of aprotinin at any time prior to Screening (e.g., Trasylol, any type or dose).
- Administration of thyroid preparations or thyroxine (except in subjects on stable replacement therapy) within 6 weeks prior to Screening.
- Administration of systemic long-acting corticosteroids within two months or prolonged use (more than one week) of other systemic corticosteroids or inhaled corticosteroids (if daily dosage is > 1,000 μg equivalent beclomethasone) within 30 days prior to Screening. Intra-articular and/or topical corticosteroids are not considered systemic.
- 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), and immunosuppressive or immunomodulating agents.
- Subject is on a weight loss program and is not in the maintenance phase, or subject has started weight loss medication (e.g., orlistat or liraglutide), within 8 weeks prior to Screening. Subjects who have had bariatric surgery are also excluded.
- Subject is pregnant or breast-feeding.
- Subject has a Screening systolic blood pressure ≥165 mmHg or diastolic blood pressure ≥100 mmHg. Subjects will be allowed to take a BP rescue medication.
- 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.
- Any clinically significant ECG abnormality at Screening or cardiovascular disease. Clinically significant cardiovascular disease will include:
- History of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to Screening,
- History of or currently have New York Heart Associate Class II-IV heart failure prior to Screening, or
- One or more contraindications to metformin.
- At the Principal Investigator's discretion, any condition or other factor that is deemed unsuitable for subject enrollment into the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Orange County Research Center
Tustin, California, 92780
About this study
Official title: A Phase 2a, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, 3-Way Crossover Study to Compare Safety, Efficacy, and Pharmacodynamics of Single and Multiple Doses of ORMD-0801 in Adult Subjects With Type 2 Diabetes Mellitus
This is a four-way crossover (non-parallel) study with each subject receiving three of the four arms. The study will enroll approximately 30 adult subjects with T2DM from age 20 to 75 inclusive.
Following a 7-10 day Screening period, eligible subjects will enter a 3-day single-blind placebo run-in. On Day 4, each subject will be randomized to a treatment sequence that will include three treatment assignments for each of three treatment Periods according to the randomization scheme.
Read the detailed description
Following the screening, eligible subjects entered a 3-day, single-blind placebo run-in. On Day 4, each subject was randomized to a treatment sequence that included three treatment assignments for each of three treatment Periods according to the randomization scheme.
Pre-assignment Details The number of participants receiving each Intervention, in each Period, is reported.
Subjects received the randomized treatment from Day 4 through Day 8. There was a 24-hour single-blind placebo washout on Day 9. Each subject received placebo for one of the three treatment periods. Each subject also received 1 of the 3 active doses randomly in each of the two other treatment periods respectively. The dosing order is random.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- ORMD-0801 (qd), ORMD-0801 (bid), ORMD-0801 (tid), Placebo
- Keywords
- Oral Insulin, DM T2 (Diabetes Mellitus Type 2)
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORMD-0801 (qd)Drug
Also called Oral Insulin
Dose 1 = ORMD-0801 (qd)
ORMD-0801 (bid)Drug
Also called Oral Insulin
Dose 2 = ORMD-0801 (bid)
ORMD-0801 (tid)Drug
Also called Oral Insulin
Dose 3 = ORMD-0801 (tid)
PlaceboOther
Also called fish oil
fish oil placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Active comparator | Placebo (fish oil) Receives: Other: Placebo |
| Dose1 | Active comparator | Dose 1 ORMD-0801 (qd) Receives: Drug: ORMD-0801 (qd) |
| Dose2 | Active comparator | Dose 2 ORMD-0801 (bid) Receives: Drug: ORMD-0801 (bid) |
| Dose 3 | Active comparator | Dose 3 ORMD-0801 (tid) Receives: Drug: ORMD-0801 (tid) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glucose Levels Between Pre-treatment and End of Treatment as Measured by 24-hour Continuous Glucose Monitoring (CGM)
Measure the change in Glucose (mg/dL) by 24 hour CGM between Day3 and Day8 (Change in mg/dL between run-in and Day 5 of Active treatment)
Measured: Day 3 (run-in) and Day 8 (Day 5 of Active treatment)
Secondary outcomes (3)
Calculate the C-peptide Ratio for Single and Multiple Doses of ORMD-0801 vs Placebo.
For each dose, calculate the ratio of the C-Peptide measurement area-under-the-curve (ng-hr/mL) Day 8 to the C-peptide measurement area-under-the-curve (ng-hr/mL) Day 3. This ratio is called the C-peptide Ratio.
Measured: Day 3 and Day 8
The Number Hypoglycemic Events for Single and Multiple Doses of ORMD-0801 vs Placebo
The number of safety parameter hypoglycemic events for single and multiple doses of ORMD-0801 vs placebo.
Measured: Day 3 through Day 8 of treatment
Calculate the Difference Between Values of Pre-treatment and End-of-treatment Mean Daytime CGM Glucose
Calculate the difference between pre-treatment (Day 3) and end of treatment (Day 8) mean daytime CGM glucose for single and multiple doses of ORMD-0801 vs placebo.
Measured: Day 3 and Day 8 (two timepoints)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2016 (estimated)
- Study startOct 2016
- Primary completion24 Feb 2017
- Study completion15 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oramed, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Integrium
- Responsible party
- Sponsor
- Investigators
- Joel M Neutel, M. D., Principal investigator, Orange County Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02954601
- Sponsor's protocol ID
- ORA-D-012
- Status last verified
- Jul 2018
- First submitted
- 13 Oct 2016
- Last updated
- 12 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, 3-Way Crossover Study to Compare Safety, Efficacy, and Pharmacodynamics of Single and Multiple Doses of ORMD-0801 in Adult Subjects With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02954601
- Acronym / sponsor ID
- ORA-D-012
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Oral Insulin, DM T2 (Diabetes Mellitus Type 2)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Oramed, Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Integrium
- Study start
- Oct 2016
- Primary completion
- 24 Feb 2017 (actual)
- Study completion
- 15 Mar 2017 (actual)
- First posted
- 3 Nov 2016 (estimated)
- Results
- Posted 12 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a four-way crossover (non-parallel) study with each subject receiving three of the four arms. The study will enroll approximately 30 adult subjects with T2DM from age 20 to 75 inclusive.
Following a 7-10 day Screening period, eligible subjects will enter a 3-day single-blind placebo run-in. On Day 4, each subject will be randomized to a treatment sequence that will include three treatment assignments for each of three treatment Periods according to the randomization scheme.
Detailed description
Following the screening, eligible subjects entered a 3-day, single-blind placebo run-in. On Day 4, each subject was randomized to a treatment sequence that included three treatment assignments for each of three treatment Periods according to the randomization scheme.
Pre-assignment Details The number of participants receiving each Intervention, in each Period, is reported.
Subjects received the randomized treatment from Day 4 through Day 8. There was a 24-hour single-blind placebo washout on Day 9. Each subject received placebo for one of the three treatment periods. Each subject also received 1 of the 3 active doses randomly in each of the two other treatment periods respectively. The dosing order is random.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Active comparator | Other: PlaceboPlacebo (fish oil) |
| Dose1 | Active comparator | Drug: ORMD-0801 (qd)Dose 1 ORMD-0801 (qd) |
| Dose2 | Active comparator | Drug: ORMD-0801 (bid)Dose 2 ORMD-0801 (bid) |
| Dose 3 | Active comparator | Drug: ORMD-0801 (tid)Dose 3 ORMD-0801 (tid) |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female subjects, age 20 to 75 years, inclusive with type 2 diabetes mellitus.
- At Visit 2/Period 1/Day 1, subjects will have been treated for their diabetes by metformin (≥1000 mg/day; any type and regimen), metformin and a DPP-4 inhibitor ( Dipeptidyl-Peptidase)-4), metformin and an SGLT-2 (Sodium-glucose co-transporter 2) inhibitor, metformin and TZD (Thiazolidinediones), or metformin and sulfonylurea. Subjects will have been on a stable regimen of metformin (defined as the same metformin dose and type) and other treatments for at least 8 weeks prior to Visit 2/Period 1/Day 1.
- Body Mass Index (BMI) between 25 and 40 kg/m2, inclusive, at Screening.
- Hemoglobin A1c (HbA1c) between ≥7.5 and ≤10.5% at Screening.
- Fasting serum glucose greater than or equal to 126 mg/dL at Screening.
Key exclusion criteria (33 listed)
- Usage of anti-diabetic agents other than metformin, sulfonylurea, SGLT-2 inhibitors, TZD, or DPP-4 inhibitors within 6 weeks prior to Visit 2/Period 1/Day 1.
- Presence of any clinically significant endocrine disease according to the Investigator (euthyroid subjects on replacement therapy will be included if the dosage of thyroxine is stable for at least six weeks prior to Screening).
- Clinical diagnosis of type 1 diabetes.
- Fasting serum glucose >300 mg/dL at Screening; a single repeat test is allowable.
- Evidence of unawareness of hypoglycemia, a documented plasma glucose ≤50 mg/dL in the absence of symptoms of hypoglycemia at Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ORMD-0801 (qd)Also: Oral InsulinDose 1 = ORMD-0801 (qd) | Drug | Dose1 |
| ORMD-0801 (bid)Also: Oral InsulinDose 2 = ORMD-0801 (bid) | Drug | Dose2 |
| ORMD-0801 (tid)Also: Oral InsulinDose 3 = ORMD-0801 (tid) | Drug | Dose 3 |
| PlaceboAlso: fish oilfish oil placebo | Other | Placebo |
Primary outcome
Change in Glucose Levels Between Pre-treatment and End of Treatment as Measured by 24-hour Continuous Glucose Monitoring (CGM)
Time frame: Day 3 (run-in) and Day 8 (Day 5 of Active treatment)
Measure the change in Glucose (mg/dL) by 24 hour CGM between Day3 and Day8 (Change in mg/dL between run-in and Day 5 of Active treatment)
3 secondary outcomes
Calculate the C-peptide Ratio for Single and Multiple Doses of ORMD-0801 vs Placebo.
Time frame: Day 3 and Day 8
The Number Hypoglycemic Events for Single and Multiple Doses of ORMD-0801 vs Placebo
Time frame: Day 3 through Day 8 of treatment
Calculate the Difference Between Values of Pre-treatment and End-of-treatment Mean Daytime CGM Glucose
Time frame: Day 3 and Day 8 (two timepoints)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joel M Neutel, M. D. principal investigator
Orange County Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ORMD-0801 (qd), ORMD-0801 (bid) and ORMD-0801 (tid) in people with Type 2 Diabetes Mellitus, run by Oramed, Ltd. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glucose Levels Between Pre-treatment and End of Treatment as Measured by 24-hour Continuous Glucose Monitoring (CGM) (time frame: Day 3 (run-in) and Day 8 (Day 5 of Active treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2018.