A Study to Determine the Absorption of Peroral Insulin in Dextran Matrix (ORA3) (ORA3)

A Placebo-controlled Study of Insulin Absorption in Healthy Volunteers After Single-dose Oral Administration of Insulin in Dextran Matrix

A pharmacokinetic study on the absorption of perorally delivered insulin in dextran matrix after single dose administration.

Study Overview

• Status: Suspended
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin in dextran matrix capsule (and placebo)

Detailed Description

The study is a single blind, cross over study where each subject will receive a a single active dose (200 IU) of insulin in dextran matrix and placebo on two different experimental days.

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • Karolinska Trial Alliance (KTA), Phase I Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects, age 18-40 years.
• Fasting blood glucose within the range 4.0-6.0 mmol/L at Screening, and on Day 1 before dosing ≥ 4 mmol/L. However, the subject should not be excluded from the study if the blood glucose is out of this range once the treatment period has started.
• Body Mass Index (BMI) of 20-27 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 ≤ 139/89 mm Hg diastolic/systolic, or at the discretion of the investigator
• 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.
• Negative laboratory screen for Hepatitis B (HBsAg and anti-HBc antibodies), Hepatitis C (anti HCV) and HIV (1&2).
• Willing to refrain from consuming alcohol 48 hours prior to dosing and throughout the period of sample collection.
• Not on any prohibited medication (See section 8.9), or at the discretion of the investigator.

Exclusion Criteria:

• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, 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, with the exception of basal cell or squamous cell carcinoma of the skin that has been excised more than one year ago with no evidence of recurrence
• 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.
• Other medical conditions, drug treatments or significant medical problems that would preclude participation in a clinical trial that, in the opinion of the investigator, disqualifies the subject.
• Participation in a clinical trial within the prior 3 months
• History of GI surgery (other than appendectomy) 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 recent adult history of clinically significant allergic reaction to any drug.
• History of polyps in the gastrointestinal tract.
• Known to have had a substance abuse (drug or alcohol) problem within the previous 5 years
• Alcohol use within 48 hours prior to visits to the study unit.
• 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) within 48 hours prior to visits to the study unit.
• Donation of plasma within 7 days prior to the first dose.
• Donation of blood within 3 months prior to the first dose
• Difficulty in swallowing capsules.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Insulin in Dextran Matrix; A group consisting of male healthy volunteers will be given placebo and one single dose of insulin in dextran matrix, for estimation of post-dose relative bioavailability.	Drug: Insulin in dextran matrix capsule (and placebo); Single dose capsule (and placebo)
Placebo Comparator: Placebo; A group consisting of male healthy volunteers will be given placebo and one single dose of insulin in dextran matrix, for estimation of post-dose relative bioavailability.	Drug: Insulin in dextran matrix capsule (and placebo); Single dose capsule (and placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic variable: insulin	Estimation of insulin AUC and Cmax post dose-administration	3-5 hours

Collaborators and Investigators

• Sponsor: Bows Pharmaceuticals AG
• Investigators: Principal Investigator: Nabil Al-Tawil, M.D.; Ph.D., Karolinska Trial Alliance, Stockholm

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Anticipated): August 1, 2010
• Study Completion (Anticipated): October 1, 2010

Study Registration Dates

• First Submitted: April 29, 2010
• First Submitted That Met QC Criteria: April 30, 2010
• First Posted (Estimate): May 3, 2010

Study Record Updates

• Last Update Posted (Estimate): October 5, 2010
• Last Update Submitted That Met QC Criteria: October 3, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: diabetes; hypoglycemia; blood glucose; hyperglycemia; dextran; blood insulin; oral delivery; portal delivery
• Additional Relevant MeSH Terms: Anticoagulants; Plasma Substitutes; Blood Substitutes; Dextrans
• Other Study ID Numbers: ORA3-2010-019098-14