Diabetes MellitusPhase 1/2ORA2NCT00990444
A Two Part Study of Peroral Insulin in Type 2 Diabetes
A Phase 1/2 study testing Insulin in Dextran Matrix in people with Diabetes Mellitus, run by Bows Pharmaceuticals AG at 1 site in Sweden.
Trial summary
Insulin is normally not bioavailable when taken through the oral route, as degradation of the molecule may occur both in the ventricle and in the intestine. Oral administration with uptake from the lesser intestine would offer major advantages if made possible. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Insulin in Dextran Matrix
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteSweden
- Study dates
- Sep 2009to Dec 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects with Type 2 diabetes who were diagnosed for a minimum of 6 months, age 30-65 years.
- Subjects on a stable dose of metformin for at least two months with a total daily dose of
- ≤ 2600 mg/day.
- Subjects demonstrating an insulin resistance value (IR) lower than 3 based on the HOMA-2 model (University of Oxford, 2004) at Screening 2.
- Hemoglobin A1c <9%.
- Fasting capillary blood glucose within the range 6.0-9.0 mmol/L (108-162 mg/dL) at Screening 1, Screening 2 and Randomization visit. For study Part 1 only, the maximum and minimum of these three measurements may not differ by more than 2 mmol/L.
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- Body Mass Index (BMI) of 25-32 kg/m2
- Medically stable as determined by history and physical examination, including vital signs.
- Screening laboratory tests must be within normal range or judged as not clinically significant by Principal investigator/Subinvestigator.
- Negative urine ketoacidosis test
- ECG including QTcB shows no clinically significant abnormality or acute ischemia
- Supine BP ≤ 160/100 mm Hg diastolic/systolic.
- Able to adhere to the study visit schedule, and to understand and comply with other protocol requirements.
- Capable of giving informed consent, which must be obtained prior to any screening procedures.
- Non user of tobacco products for a minimum of 6 months prior to the first dose.
- Negative urine screen for drugs of abuse and an alcohol breath test at screening and check in.
- Negative laboratory screen for Hepatitis B (HBsAg and anti-HBc antibodies), Hepatitis C (anti HCV) and HIV (1\&2).
- Not on any prohibited medication, including alcohol.
- Female subjects willing to use adequate method of contraception from the time of the first dose until one month after the last dose.
- Willing to eat standard meal in accordance with the protocol.
Who cannot join
- History of significant coronary disease or renal failure
- Other significant medical problems that would preclude participation in a clinical trial
- Participation in a clinical trial within the prior 3 months
- History of GI surgery or known GI motility disorders.
- History of a serious infection, including but not limited to hepatitis, pneumonia, or pyelonephritis, or have been hospitalized or received intravenous antibiotics for an infection, during the previous two months.
- A chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (bronchiectasis), sinusitis, recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), open skin wound, or ulcer.
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- Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine (other than diabetes), pulmonary, cardiac, neurologic, or cerebral disease, or any other condition which increases risk of participation in this trial in the opinion of the investigator.
- Currently known malignancy or a history of malignancy within the previous 5 years.
- History of polyps in the gastrointestinal tract.
- Known to have had a substance abuse (drug or alcohol) problem within the previous 5 years
- Unable to undergo venipunctures for study purposes because of poor tolerability or lack of easy access.
- Engaging in any strenuous exercise (such as running or weight lifting or playing any team sports such as soccer for 48 hours prior to admission to the inpatient unit and no strenuous exercise will be permitted for the duration of the study (applies to both part 1 and part 2).
- Donation or loss of 400 ml blood or more within 3 months prior to the first dose or donation of plasma within 7 days prior to the first dose.
- Difficulty in swallowing capsules.
- A recent adult history of clinically significant allergic reaction to any drug.
- Any other medical condition that, in the opinion of the investigator, disqualifies the subject.
- Female subject with positive pregnancy test at screening, Day -1.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Karolinska Trial Alliance, Phase I Unit
Stockholm, Solna, Stockholm, 17176
About this study
Official title: A Double-Blind Two Part Placebo-Controlled Study Consisting of a Single Ascending and Multiple-Dose Tolerance Study of Peroral Insulin in Patients With Type 2 Diabetes
Insulin is normally not bioavailable when taken through the oral route, as degradation of the molecule may occur both in the ventricle and in the intestine. Oral administration with uptake from the lesser intestine would offer major advantages if made possible. It would offer a simple non-injection method to administer insulin in connection with a meal and absorbed insulin would enter the blood stream and mimic the natural distribution in the body with a first pass through the liver. The sponsor of this study has developed a novel oral insulin formulation that is based on a proprietary dextran matrix. The investigational drug is a capsule containing 100 IU of human insulin in dextran matrix.
The primary objective of this study is to establish the safety, tolerance and PD profile (i.e. pharmacodynamic parameters for glucose and insulin) of peroral insulin in dextran matrix in patients with type 2 diabetes.
The phase I/II study protocol consists of two parts; part 1 (dose finding) and part 2 (dose verification). In study part 1 single escalating doses of oral insulin or placebo is given to the test subjects. Capillary blood glucose is used to assess the insulin effect. Subsequently, in study part 2, the investigational drug will be administered 3 times daily on 6 consecutive days. The starting dose of part 2 will be the lowest effective dose found in study part 1. Dose escalation will be done in increments of 100 IU. The total number of subjects will be 32 (for part 1 and 2 combined).
- Conditions
- Diabetes Mellitus
- Being tested
- Insulin in Dextran Matrix
- Keywords
- blood glucose, blood insulin, dextran, diabetes, hyperglycemia, hypoglycemia, oral delivery, portal delivery
- Medical subject headings
- Diabetes Mellitus, Hyperglycemia, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin in Dextran MatrixDrug
Also called Peroral insulin
Fixed dose capsule with 100 IU of insulin in dextran matrix. Investigational drug or placebo are administered in conjunction with food intake on a background of metformin.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Treatment with vehicle capsule containing excipients only, taken in conjunction with standard meal. Receives: Drug: Insulin in Dextran Matrix |
| Oral Insulin in Dextran | Active comparator | Treatment with fixed insulin dose taken in conjunction with standard meal. Receives: Drug: Insulin in Dextran Matrix |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the lowest dose of oral insulin in dextran matrix that produces a significant lowering of post-prandial blood glucose.
Measured: 6 hours
Secondary outcomes (1)
To establish the dose(s) when administered in a multi-dose fashion that lowers plasma glucose levels versus placebo in patients with Type 2 diabetes
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionSep 2010 (estimated)
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bows Pharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Nabil Al-Tawil, M.D.; Ph.D., Principal investigator, Karolinska Trial Alliance
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00990444
- Sponsor's protocol ID
- ORA2-2009-010660-42
- Acronym
- ORA2
- Status last verified
- Oct 2010
- First submitted
- 5 Oct 2009
- Last updated
- 5 Oct 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Two Part Placebo-Controlled Study Consisting of a Single Ascending and Multiple-Dose Tolerance Study of Peroral Insulin in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00990444
- Acronym / sponsor ID
- ORA2 / ORA2-2009-010660-42
- Conditions
- Diabetes Mellitus
- Keywords
- blood glucose, blood insulin, dextran, diabetes, hyperglycemia, hypoglycemia, oral delivery, portal delivery
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Suspended
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Bows Pharmaceuticals AGIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Sep 2010 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 6 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Insulin is normally not bioavailable when taken through the oral route, as degradation of the molecule may occur both in the ventricle and in the intestine. Oral administration with uptake from the lesser intestine would offer major advantages if made possible. It would offer a simple non-injection method to administer insulin in connection with a meal and absorbed insulin would enter the blood stream and mimic the natural distribution in the body with a first pass through the liver. The sponsor of this study has developed a novel oral insulin formulation that is based on a proprietary dextran matrix. The investigational drug is a capsule containing 100 IU of human insulin in dextran matrix.
The primary objective of this study is to establish the safety, tolerance and PD profile (i.e. pharmacodynamic parameters for glucose and insulin) of peroral insulin in dextran matrix in patients with type 2 diabetes.
The phase I/II study protocol consists of two parts; part 1 (dose finding) and part 2 (dose verification). In study part 1 single escalating doses of oral insulin or placebo is given to the test subjects. Capillary blood glucose is used to assess the insulin effect. Subsequently, in study part 2, the investigational drug will be administered 3 times daily on 6 consecutive days. The starting dose of part 2 will be the lowest effective dose found in study part 1. Dose escalation will be done in increments of 100 IU. The total number of subjects will be 32 (for part 1 and 2 combined).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Insulin in Dextran MatrixTreatment with vehicle capsule containing excipients only, taken in conjunction with standard meal. |
| Oral Insulin in Dextran | Active comparator | Drug: Insulin in Dextran MatrixTreatment with fixed insulin dose taken in conjunction with standard meal. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Male and female subjects with Type 2 diabetes who were diagnosed for a minimum of 6 months, age 30-65 years.
- Subjects on a stable dose of metformin for at least two months with a total daily dose of
- ≤ 2600 mg/day.
- Subjects demonstrating an insulin resistance value (IR) lower than 3 based on the HOMA-2 model (University of Oxford, 2004) at Screening 2.
- Hemoglobin A1c <9%.
Key exclusion criteria (17 listed)
- History of significant coronary disease or renal failure
- Other significant medical problems that would preclude participation in a clinical trial
- Participation in a clinical trial within the prior 3 months
- History of GI surgery or known GI motility disorders.
- History of a serious infection, including but not limited to hepatitis, pneumonia, or pyelonephritis, or have been hospitalized or received intravenous antibiotics for an infection, during the previous two months.
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 |
|---|---|---|
| Insulin in Dextran MatrixAlso: Peroral insulinFixed dose capsule with 100 IU of insulin in dextran matrix. Investigational drug or placebo are administered in conjunction with food intake on a background of metformin. | Drug | Oral Insulin in Dextran, Placebo |
Primary outcome
Identification of the lowest dose of oral insulin in dextran matrix that produces a significant lowering of post-prandial blood glucose.
Time frame: 6 hours
1 secondary outcome
To establish the dose(s) when administered in a multi-dose fashion that lowers plasma glucose levels versus placebo in patients with Type 2 diabetes
Time frame: 8 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2010.
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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.
Nabil Al-Tawil, M.D.; Ph.D. principal investigator
Karolinska Trial Alliance
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Insulin in Dextran Matrix in people with Diabetes Mellitus, run by Bows Pharmaceuticals AG at 1 site in Sweden.
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 20 inclusion and 17 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: paused, as of the sponsor's last update on 5 Oct 2010. 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 Sweden. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
Identification of the lowest dose of oral insulin in dextran matrix that produces a significant lowering of post-prandial blood glucose. (time frame: 6 hours). 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 5 Oct 2010.