The most recent safety data I could find only measures pulmonary efficiency at the beginning and end of the study, which was three months. Not sure if more patients are needed or longer time periods. Obviously, the latter is more onerous. From the Annals of Internal Medicine:
>>BRIEF COMMUNICATIONS
Inhaled Human Insulin Treatment in Patients with Type 2 Diabetes Mellitus
William T. Cefalu, MD; Jay S. Skyler, MD; Ione A. Kourides, MD; William H. Landschulz, MD, PhD; Cecile C. Balagtas, PhD; Shu-Lin Cheng, PhD; Robert A. Gelfand, MD, for the Inhaled Insulin Study Group
Background: Despite demonstrated benefits, intensive insulin therapy has not gained widespread clinical acceptance for several reasons: Multiple daily injections are inconvenient, adherence is a concern, and the time-activity profile may not mimic normal insulin secretion. As such, alternate means of administering insulin are being evaluated.
Objective: To assess the efficacy and safety of pulmonary delivery of insulin in type 2 diabetic patients who require insulin.
Design: Randomized, open-label, 3-month study consisting of a screening visit, a 4-week baseline lead-in phase, and a 12-week treatment phase.
Setting: General clinical research center and outpatient research clinics.
Patients: 26 patients (16 men, 10 women) with type 2 diabetes (average age, 51.1 years; average duration of diabetes, 11.2 years).
Intervention: Patients received inhaled insulin before each meal plus a bedtime injection of ultralente insulin, performed home glucose monitoring, and had weekly adjustment of insulin dose; target level for preprandial plasma glucose was 5.55 to 8.88 mmol/L (100 to 160 mg/dL).
Measurements: Glycemic control (hemoglobin A1c level) obtained at baseline and monthly for 3 months. Pulmonary function tests were done at baseline and at the end of the study.
Results: Inhaled insulin treatment for 3 months significantly improved glycemic control compared with baseline: Mean hemoglobin A1c levels decreased by 0.0071 0.0072 (0.71% 0.72%). Patients experienced an average of 0.83 mild to moderate hypoglycemic event per month; no severe events were recorded. Patients showed no significant weight gain or change in pulmonary function compared with baseline.
Conclusions: Pulmonary delivery of insulin in type 2 diabetic patients who require insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects. Larger-scale studies are ongoing to provide long-term efficacy and safety data.
Ann Intern Med. 2001;134:203-207.
Author and Article Information
From University of Vermont College of Medicine, Burlington, Vermont; University of Miami Medical Center, Miami, Florida; and Pfizer Central Research, Groton, Connecticut.
For members of the Inhaled Insulin Study Group, see Appendix.
Presented in abstract form as an oral presentation at the Annual Meeting of the American Diabetes Association, Chicago, Illinois, June 1998.
Acknowledgment: The authors thank Becky Aksdal for her skillful preparation of the manuscript and her valuable editorial assistance.
Grant Support: By Pfizer, Inc. Technology used for this study was licensed from Inhale Therapeutic Systems, San Carlos, California.
Requests for Single Reprints: William T. Cefalu, MD, University of Vermont College of Medicine, UHC Campus, Arnold 3433, One South Prospect Street, Burlington, VT 05401.
Current Author Addresses: Dr. Cefalu: University of Vermont College of Medicine, UHC Campus, Arnold 3433, One South Prospect Street, Burlington, VT 05401.
Dr. Skyler: University of Miami Medical Center, 1500 NW 12th Avenue, Suite 1012 East, Miami, FL 33136.
Dr. Kourides: Clinical and Scientific Affairs, Pfizer, Inc., 235 East 42nd Street, New York, NY 10017.
Drs. Landschulz and Gelfand: Department of Clinical Research, Pfizer, Inc., Eastern Point Road, Groton, CT 06340-8030.
Drs. Balagtas and Cheng: Department of Biometrics and Data Management, Pfizer, Inc., Eastern Point Road, Groton, CT 06340.<<
snip
According to Ian Stromberg on the firesales thread, EMIS made noise about safety issues with pulmonary delivery a couple of quarters ago, but it doesn't sound very specific. Also, another study published this summer (ARDM's PIII results) mentions increased serum binding of the pulmonary insulin by antibodies, but noted no clinical impact from this.
Message 15991337
Note that this is a six month study. What I can't figure out is this: Is this a big issue? Is it what EMIS is talking about and what's causing the delay? If it didn't show up in 3 month studies, but did in six month studies, how long will the FDA want the next studies to be? Perhaps this is why ARDM CEO Thompson said that they were not ceding the achievement of being the first to launch pulmonary insulin to INHL.
Anybody got anything solid that's more up to date?
Cheers, Tuck |
