Clinical trial NCT01021891: 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)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Technosphere® Insulin Inhalation Powder
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2009-11-30
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 30 days
Secondary outcomes:
measure: Efficacy endpoints include: additional PK parameters of serum insulin and serum FDKP, Pharmacodynamic parameters of sersum insulin, safety of T/I
timeFrame: 30 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Assoc PA
state: Texas
city: Graz
country: Austria
facility: Medical University Graz
city: Zuidlaren
country: Netherlands
facility: University Medical Centre Groningen
city: Manchester
country: United Kingdom
facility: Medicines Evaluation Unit (MEU)
state: England
city: Manchester
country: United Kingdom
facility: ICON Development Solutions
Study officials:
affiliation: MannKind Corp
name: Anders Boss, MD
role: STUDY_CHAIR
References: