Pharmacokinetics/Dynamics of Basal (Continuous) Insulin Infusion Administered Either Intradermally or Subcutaneously

Diabetes Mellitus, Type 2 Clinical Trial

Official title: A Mono-center, Open Label, Randomised 2-period Crossover Study to Compare the Pharmacokinetics and Pharmacodynamics of Continuous Insulin Infusion Administered Either Intradermally or Subcutaneously in Subjects With Type 1 Diabetes Mellitus

Status Completed

Clinical Trial Summary

The primary objective of this study will be to assess the PK/PD responsiveness of basal ID administered insulin compared to SC, and to determine the safety and local tolerability of extended (two six-hour periods) microneedle insulin delivery (MID) infusion. The primary endpoint will be the PK response to changes in rapid-acting insulin basal infusion rate.

Faster PK transitions coupled with faster PD responsiveness could provide clinical benefit, compared to current subcutaneous insulin infusion. In addition, for nocturnal basal pumping, more rapid insulin offset could decrease the occurrence rate and severity of hypoglycemic episodes.

Clinical Trial Description

Twenty (20) male T1 diabetic subjects will be studied under manual partial glucose clamp conditions over a 16 hour infusion period (approximately 36 hours of overall time in clinic). Subjects will be admitted to the clinic the night before their study visit for overnight stabilization in which, via insulin and/or glucose infusions, blood glucose will be stabilized to approximately 140 mg/dL. Subjects will receive as background IV Humulin insulin with an initial dose equivalent to one-half of their usual daily basal insulin dose. In the morning the subjects will start the experimental intervention and have administered a low rate stair-stepped Lispro insulin infusion profile via an infusion pump (Harvard Syringe Pump, Harvard Apparatus).

The profile is designed to examine the initial "on" rate for microneedle insulin delivery, the transition time between basal rate changes and the "off-rate" after insulin cessation. Subjects will receive the same profile by SC infusion on a second clinic day in a randomized order. PK endpoints will be established using timed blood samples. Safety and tolerability at the local infusion site will also be recorded.

In parallel, using a commercially available insulin pump (One Touch "Ping" Insulin Pump, Animas) and an infusion set (either the RCS or a commercially available SC insulin infusion set); a second infusion of insulin diluent will be used to assess the feasibility of longer-term ID infusions (16 hours) as compared to SC.

During each infusion the pumps will control the fluid delivery rate and volume. In addition an in-line pressure transducer will record the pressure and transfer the information to a laptop computer.

Primary Objective:

• To define the PK profile of initiation, rate change, and discontinuation of continuously infused basal insulin administered either intradermally or subcutaneously over two separate infusion periods.

Secondary Objectives:

• Determine the PD effect of the infused insulin as measured by time to glucose rebound following discontinuation of test insulin infusion.

• Assess the safety and tolerability of intradermally infused insulin over two six-hour periods.

• Assess the feasibility of the research catheter set (RCS) for longer-term ID infusion ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2

• NCT number: NCT01061216
• Study type: Interventional
• Source: Becton, Dickinson and Company
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2010
• Completion date: March 2010