A Study to Evaluate Insulin in the Blood After Inhalation of a Dry Powder Insulin Formulation (Called Technosphere®/Insulin) in Non-diabetic Patients With & Without Chronic Obstructive Pulmonary Disease (COPD)

A Phase 1b, Single-Dose, Open-Label, Parallel, Controlled Pharmacology Trial of Inhaled Technosphere®/Insulin in Non-Diabetic Subjects With COPD Versus Matched Non-Diabetic Subjects Without COPD.

Trial will include 40 subjects and consists of 3 visits: Screening, Treatment and Follow up. A euglycemic clamp procedure and Technosphere®/Insulin (T/I) administration will occur at Visit 2 for both COPD and non COPD subjects.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Technosphere®/Insulin

Detailed Description

Trial objectives are to evaluate the impact of a defined lung disease (COPD) on pharmacokinetic parameters of insulin and fumaryl diketopiperazine (FDKP) after inhalation of Technosphere®/Insulin (T/I), the investigational medicinal product. 40 non diabetic subjects, 20 COPD and 20 age/gender/BMI-matched non COPD subjects will participate in 3 visits: Visit 1 (screening), Visit 2 (subjects will undergo a euglycemic clamp procedure and be dosed with T/I) and Visit 3 (follow up visit).

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A-8036
    • Medical University Graz
• Netherlands
  • Zuidlaren, Netherlands, 9470 AE
    • University Medical Centre Groningen
• United Kingdom
  • Manchester, United Kingdom, M15 6SH
    • ICON Development Solutions
  • England
    • Manchester, England, United Kingdom, M23 9QZ
      • Medicines Evaluation Unit (MEU)
• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease Research Assoc PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects minimum 18 and maximum 70 years of age
• Body Mass Index (BMI) = 36 kg/m2
• Subjects with COPD: Diagnosis of COPD (emphysema and/or chronic bronchitis),
• smoking history =10 years, chronic cough present intermittently or daily with or without sputum and/or dyspnea upon exertion.
• Subjects with COPD: Pulmonary Function Tests - FEV1 =50% (NHANES) III
• Predicted; FEV1/FVC < 70 % (NHANES) III; TLC =80% of Predicted (ITS) and DLco(unc) =50% of Predicted (Miller)
• Subjects without COPD: PFTs: FEV1 = 70% NHANES III Predicted; TLC =80% of
• Predicted (ITS) and DLco(unc) =80% of Predicted (Miller)

Exclusion Criteria:

• History of pre-diabetes or diabetes
• Previous or current treatment with any anti-diabetic drugs
• Serum creatinine > 2.0 mg/dL in males and > 1.8 mg/dL in females
• Active smokers defined as having smoked their last cigarette, pipe, and/or cigar without the previous 6 months
• Previous exposure to any inhaled insulin product or investigational medicines/devices within the previous 30 days prior to entry or participation
• Clinically significant major organ disease
• Female subjects of childbearing potential not practicing adequate birth control
• Subjects with COPD: Significant improvement in pre-to post-bronchodilator spirometry (defined as an increase of 12% AND 200 mL in either FVC or FEV1);
• Any clinically important pulmonary disease except mild or moderate COPD
• Subjects without COPD: Any important pulmonary disease confirmed by pulmonary function testing and/or radiologic findings

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-Diabetic Subj. w/o COPD; Single dose, 30 units	Drug: Technosphere®/Insulin
Experimental: Non-Diabetic Subj. with COPD; Single dose, 30 units	Drug: Technosphere®/Insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the pharmacokinetic disposition of serum insulin and serum fumaryl diketopiperazine following dosing with 30 U T/I, as measured via Area Under the Curve serum insulin and AUC 0-480 min serum FDKP	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy endpoints include: additional PK parameters of serum insulin and serum FDKP, Pharmacodynamic parameters of sersum insulin, safety of T/I	30 days

Collaborators and Investigators

• Sponsor: Mannkind Corporation
• Investigators: Study Chair: Anders Boss, MD, MannKind Corp

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 27, 2009
• First Posted (Estimate): November 30, 2009

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: December 13, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Technosphere® Insulin Inhalation Powder
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: MKC-TI-015; EudraCT Number: 2007-002818-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No