Clinical trial NCT00982254: Oral Insulin: A Comparison With Subcutaneous Regular Human Insulin in Patients With Type 2 Diabetes
Official title: A Comparison of the Pharmacodynamic and Pharmacokinetic Properties of Oral Insulin vs. s.c. Regular Insulin in Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: Type 2 Diabetes
Oral Insulin
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Profil Institut für Stoffwechselforschung GmbH
Sponsor class: INDUSTRY
Collaborators: name: Emisphere Technologies, Inc.
First posted: 2009-09-23
Enrollment: 10
Sex: MALE
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study compared the pharmacokinetic and pharmacodynamic properties of an oral insulin formulation with that of a standard subcutaneous injection of regular human insulin.

Detailed description: This study was a single centre, randomized, 3-period crossover study performed in patients with type 2 diabetes. Patients received single doses of an oral insulin formulation and subcutaneous regular human insulin on separate visits.

The primary objective of this study was to compare the pharmacokinetic and pharmacodynamic properties of an oral insulin formulation with that of 15 U subcutaneous injected regular human insulin.

Pharmacokinetic and pharmacodynamic parameters including bioavailability and bioefficacy were measured during 6-hour glucose clamp experiments.

Study duration: 2 months

Eligibility criteria: Inclusion Criteria:

* Male subjects between the ages of 35 and 70 years, inclusive, with Type 2 diabetes mellitus as defined by the ADA criteria for more than one year
* Subjects must have Body Mass Index (BMI) \< 36 kg/m²
* Stable glycemic control (HbA1C \<11%)
* Subjects must be off all oral hypoglycemic agents 24 hours prior to each study dosing day and off any investigational drug for at least 4 weeks
* Subjects must refrain from strenuous physical activity beginning 72 hours prior to admission and through the duration of the study
* Subjects must be willing and able to be confined to the Clinical Research Unit as required by the protocol
* Subjects must be willing and able to provide written informed consent

Exclusion Criteria:

* History or presence of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, neurological or infectious disorders capable of altering the absorption, metabolism or elimination of drugs, or of constituting a risk factor when taking the study medication
* Subjects with gastroparesis, orthostatic hypotension and hypoglycemia unawareness (autonomic neuropathy).
* Subjects with "brittle" diabetes or predisposition to severe hypoglycemia, e.g., 2 or more serious hypoglycemic episodes (requiring another's assistance) within the past year, or any hospitalization or emergency room visit due to poor diabetic control within the past 6 months.
* Evidence of significant active hematological disease and/or cumulative blood donation of 1 unit (500 mL) or more including blood drawn during clinical trials in the last 3 months
* Positive hepatitis B (hepatitis B surface antigen) and/or hepatitis C (hepatitis C antibody) serology
* Positive HIV serology
* Evidence of significant active neuropsychiatric disease
* Known allergy to human insulin excipients contained in these products
* Regular alcohol intake greater than 28 units\*/week (male), or 21 units/week (female), or subjects unwilling to stop alcohol for the duration of the study (\* 1 unit = 8 g ethanol, ¼ liter of beer or 1 glass wine or 1 measure of spirits)
* Intake of any drug which in the evaluation of the investigator may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilisation or recovery from hypoglycaemia.
* Treatment with s.c. insulin injections.
* Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted
* Have any other condition (including drug abuse, alcohol abuse, or psychiatric disorder) that, in the opinion of the investigator, precludes the patient from following and completing the protocol.

Primary outcomes:
measure: Glucose Infusion Rate (GIR)
timeFrame: For each treatment continuously from 6 hours before dosing until 6 hours after dosing
Secondary outcomes:
measure: Plasma insulin concentration
timeFrame: For each treatment at regular times from 6 hours before dosing until 6 hours after dosing
measure: Plasma C-Peptide
timeFrame: For each treatment at regular times from 6 hours before dosing until 6 hours after dosing
measure: Adverse Events
timeFrame: For each treatment before and after end of clamp
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany
name: Tim Heise, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kapitza C, Zijlstra E, Heinemann L, Castelli MC, Riley G, Heise T. Oral insulin: a comparison with subcutaneous regular human insulin in patients with type 2 diabetes. Diabetes Care. 2010 Jun;33(6):1288-90. doi: 10.2337/dc09-1807. Epub 2010 Feb 25.