A Study Designed to Determine if the Pharmacokinetic Disposition of Inhaled Insulin Exposure is the Same for Asthmatics and Non-asthmatics

Phase 1

Completed

• Conditions: Asthma; Diabetes Mellitus
• Interventions: Drug: Technosphere Insulin Inhalation Powder; Drug: Salbutamol (Albuterol); Drug: Methacholine chloride

• Registration Number: NCT00673621
• Lead Sponsor: Mannkind Corporation

Brief Summary

This study will compare the rate and extent of absorption of TI Inhalation Powder in subjects with asthma and subjects with normal lung function. 24 eligible subjects will be enrolled into the treatment phase of the trial.

Detailed Description

Visit 1 screening will determine eligibility and obtain informed consent. At visit 2, 3 and 4 subjects inhale 1 dose of 45U TI Inhalation Powder. At visit 3 subjects inhale 2 puffs (200mcg) Albuterol prior to dosing. Only asthmatic subjects undergo visit 4 where a methacholine challenge test (MCT) is performed followed by inhalation of Albuterol then administration of TI Inhalation Powder. Each visit's dosing will occur during a hyperinsulinemic euglycemic clamp. Visit 5 is the follow up visit.

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-05-05
• Study First Submitted QC: 2008-05-05
• Study First Posted: 2008-05-07
• Primary Completion: 2008-11
• Study Completion: 2008-12
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-12
• Last Update Posted: 2012-06-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Non smoking male and female subjects = 18 and = 55 years of age with BMI = 34 kg/m2 Fasting blood glucose (FBG) < 110 mg/dL (6.1 mmol/L). Written informed consent Asthmatic Subjects: Clinical diagnosis of asthma along with defined reversibility from pre- to post-bronchodilator spirometry.

Pulmonary Function Testing for Asthmatic subjects: FEV1 > 70% (NHANES III), TLC >70% (ITS), Dlco >80% (Miller) Non-asthmatic healthy subjects: FEV1 > 80% (NHANES III), FEV1/FVC > LLN (NHANES), TLC >80% (ITS), Dlco >80% (Miller), no significant improvement from pre- to post-bronchodilator spirometry.

Exclusion Criteria

Unable and/or unlikely to comprehend how to use the investigational device in this study or to follow study instructions Change in asthma therapeutic regimen from Screening through visit 5 Exacerbation of asthma within 8 weeks prior to Screening History of diabetes mellitus Previous exposure to any inhaled insulin product other than TI inhalation Powder or similar formulation Inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria Any clinically important pulmonary disease Major organ system diseases including seizures, heart failure, uncontrolled hypertension, cancer within the past 5 years, aneurysm, liver disease, anemia or autoimmune disorder Clinically significant abnormalities on screening laboratory evaluation Female subjects who are pregnant, lactating, or planning to become pregnant during the clinical trial period or not practicing adequate birth control

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Technosphere Insulin Inhalation Powder	-
1	Salbutamol (Albuterol)	-
1	Methacholine chloride	-

Primary Outcome Measures

Name	Time	Method
AUCF 0-360 min of serum insulin	0-360 min

Trial Locations

Locations (2)

ICON Development Solutions; 🇬🇧 Manchester, United Kingdom

Medicines Evaluation Unit (MEU); 🇬🇧 Manchester, England, United Kingdom