ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Comparing Subcutaneous Rapid Acting Insulin and One Formulation of Inhaled Insulin in Subjects With Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00570687
Recruitment Status : Completed
First Posted : December 11, 2007
Results First Posted : October 16, 2014
Last Update Posted : October 16, 2014
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Intervention Drug: Technosphere Insulin
Enrollment 30

Recruitment Details

This single-center study was conducted at:

Profil Institut fur Stoffwechselforschung GmbH Hellersbergstrasse 9 D-41460 Neuss, Germany Principal Investigator: Dr. Klaus Rave

First subjects first visit: 20 September 2007 Last subject last visit: 30 January 2009

Pre-assignment Details This randomized, open-label crossover study was conducted in 2 phases: original protocol (TI 45 U, Exubera 4mg and Lispro 12 U) and amendment 1 (TI 60U or TI 90 U, and Lispro 10 U). Both original protocol and amendment 1 had screening visits, meal challenge and glucose clamp visits (with a blood-loss recovery period between them) and final visits.
Arm/Group Title Amendment 1: TI 60 U Then Insulin Lispro 10 U Amendment 1: 10 U Insulin Lispro Then 60 U TI Amendment 1: TI 90 U Then 10 U Insulin Lispro Amendment 1: 10 U Insulin Lispro Then 90 U TI Original Protocol: TI to Insulin Lispro to Exubera Original Protocol: TI to Exubera to Insulin Lispro Original Protocol: Exubera to Insulin Lispro to TI Original Protocol: Exubera to TI to Insulin Lispro Original Protocol: Insulin Lispro to TI to Exubera Original Protocol: Insulin Lispro to Exubera to TI
Hide Arm/Group Description 60 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, followed by 10 U subcutaneously administered insulin lispro 10 U subcutaneously administered insulin lispro, followed by 60 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler 90 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, followed by 10 U subcutaneously administered insulin lispro 10 U subcutaneously administered insulin lispro, followed by 90 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler 45 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, followed by 12 U of subcutaneously administered insulin lispro, and then 4 mg of Exubera administered via inhalation 45 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, followed by 4 mg of Exubera administered via inhalation, and then 12 U of subcutaneously administered insulin lispro 4 mg of Exubera administered via inhalation, followed by 12 U of subcutaneously administered insulin lispro,and then 45 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler 4 mg of Exubera administered via inhalation, followed by 45 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler,. and then 12 U of subcutaneously administered insulin lispro 12 U of subcutaneously administered insulin lispro, followed by 45 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, and then 4 mg of Exubera administered via inhalation 12 U of subcutaneously administered insulin lispro, followed by 4 mg of Exubera administered via inhalation, and then 45 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler
Period Title: Meal Challenge 1 (1 Day) - Orig Protocol
Started 0 0 0 0 3 3 3 3 3 3
Completed 0 0 0 0 3 3 3 3 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 1 (7-21 Days) - Orig Protocol
Started 0 0 0 0 3 3 3 3 3 3
Completed 0 0 0 0 3 3 3 3 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Meal Challenge 2 (1 Day) - Orig Protocol
Started 0 0 0 0 3 3 3 3 3 3
Completed 0 0 0 0 3 3 3 3 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 2 (7-21 Days) - Orig Protocol
Started 0 0 0 0 3 3 3 3 3 3
Completed 0 0 0 0 3 3 3 3 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Meal Challenge 3 (1 Day) - Orig Protocol
Started 0 0 0 0 3 3 3 3 3 3
Completed 0 0 0 0 3 3 3 3 3 3
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 3 (7-21 Days) - Orig Protocol
Started 0 0 0 0 3 3 3 3 3 3
Completed 0 0 0 0 0 0 1 0 1 0
Not Completed 0 0 0 0 3 3 2 3 2 3
Reason Not Completed
Sponsor Decision             0             0             0             0             3             3             2             3             2             3
Period Title: Clamp 1 (1 Day) - Orig Protocol
Started 0 0 0 0 0 0 1 0 1 0
Completed 0 0 0 0 0 0 1 0 1 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 4 (7-21 Days) - Orig Protocol
Started 0 0 0 0 0 0 1 0 1 0
Completed 0 0 0 0 0 0 1 0 0 0
Not Completed 0 0 0 0 0 0 0 0 1 0
Reason Not Completed
Sponsor Decision             0             0             0             0             0             0             0             0             1             0
Period Title: Clamp 2 (1 Day) - Orig Protocol
Started 0 0 0 0 0 0 1 0 0 0
Completed 0 0 0 0 0 0 1 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 5 (7-21 Days) - Orig Protocol
Started 0 0 0 0 0 0 1 0 0 0
Completed 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 1 0 0 0
Reason Not Completed
Sponsor Decision             0             0             0             0             0             0             1             0             0             0
Period Title: Meal Challenge 1 (1 Day) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 1 (7-21 Days) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Meal Challenge 2 (1 Day) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 2 (8 Weeks) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Clamp 1 (1 Day) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout 3 (7-21 Days) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Clamp 2 (1 Day) - Amendment 1
Started 4 2 2 4 0 0 0 0 0 0
Completed 4 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Amendment 1 Original Protocol Total
Hide Arm/Group Description 2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro 3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro Total of all reporting groups
Overall Number of Baseline Participants 12 18 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 18 participants 30 participants
55.3  (7.6) 54.9  (6.9) 55.1  (7.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 18 participants 30 participants
Female
3
  25.0%
3
  16.7%
6
  20.0%
Male
9
  75.0%
15
  83.3%
24
  80.0%
1.Primary Outcome
Title Time to Minimum Endogenous Glucose Production (EGP) - Meal Challenge
Hide Description Time to minimum EGP post dose
Time Frame 0-480 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Amendment 1: Subjects with type 2 diabetes; all received TI and were crossed over to lispro; 3 subjects in the 90 U TI group had insufficient data. Original protocol:Subjects with type 2 diabetes; all subjects received all doses; EGPmin could not be calculated for 1 subject for Exubera and 2 subjects for the other treatments.
Arm/Group Title Amendment 1 - TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Hide Arm/Group Description:
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
Overall Number of Participants Analyzed 3 6 12 16 17 16
Median (Full Range)
Unit of Measure: Minutes
75.0
(20 to 80)
75.0
(45 to 310)
125.0
(80 to 210)
60
(30 to 460)
160
(80 to 480)
130
(50 to 350)
2.Primary Outcome
Title Minimum EGP - Meal Challenge
Hide Description Minimum calculated EGP per subject as change from baseline
Time Frame 0-480 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Amendment 1: Subjects with type 2 diabetes; all received TI and were crossed over to lispro; 3 subjects in the 90 U TI group had insufficient data. Original protocol:Subjects with type 2 diabetes; all subjects received all doses; EGPmin could not be calculated for 1 subject for Exubera and 2 subjects for the other treatments.
Arm/Group Title Amendment 1 - TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Hide Arm/Group Description:
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
Overall Number of Participants Analyzed 3 6 12 16 17 16
Mean (Standard Deviation)
Unit of Measure: µmol/kg/min
-10.29  (4.394) -6.92  (1.584) -7.11  (2.018) -7.59  (3.015) -7.86  (2.962) -7.63  (2.709)
3.Primary Outcome
Title EGP AOC0-480 - Meal Challenge
Hide Description EGP area over the curve from 0 to 480 minutes postdose
Time Frame 0-480 minutes
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Amendment 1: Subjects with type 2 diabetes. All subjects crossed over to lispro treatment. Original protocol:Subjects with type 2 diabetes; all subjects received all doses; AOC could not be calculated for 1 subject for Exubera and 2 subjects for the other treatments.
Arm/Group Title Amendment 1 - TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Hide Arm/Group Description:
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
Overall Number of Participants Analyzed 6 6 12 16 17 16
Mean (Standard Deviation)
Unit of Measure: µmol/kg
2272.8  (266.2) 2108.7  (498.3) 2190.9  (674.5) 2129.4  (764.4) 2488.3  (845.1) 1985.9  (623.5)
Time Frame From the time the informed consent was signed to 30 days after the last study visit or study-related procedure
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Amendment 1 -TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60 U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Hide Arm/Group Description 2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro 2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro 2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro 3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro 3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro 3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
All-Cause Mortality
Amendment 1 -TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60 U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Amendment 1 -TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60 U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/6 (0.00%)      0/12 (0.00%)      0/18 (0.00%)      0/18 (0.00%)      0/18 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Amendment 1 -TI Inhalation Powder 90 U Amendment 1 - TI Inhalation Powder 60 U Amendment 1 - Insulin Lispro 10 U Original Protocol - TI Inhalation Powder 45 U Original Protocol - Exubera 4 mg Original Protocol - Insulin Lispro 12 U
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/6 (83.33%)      4/6 (66.67%)      1/12 (8.33%)      5/18 (27.78%)      1/18 (5.56%)      7/18 (38.89%)    
Gastrointestinal disorders             
Vomiting  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 1/18 (5.56%)  1 0/18 (0.00%)  0 0/18 (0.00%)  0
General disorders             
Pyrexia  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0 1/18 (5.56%)  1
Metabolism and nutrition disorders             
Hypoglycemia  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 2/18 (11.11%)  3 0/18 (0.00%)  0 4/18 (22.22%)  4
Musculoskeletal and connective tissue disorders             
Tenosynovitis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 1/18 (5.56%)  1 0/18 (0.00%)  0 0/18 (0.00%)  0
Hand fracture  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 0/18 (0.00%)  0 1/18 (5.56%)  1 0/18 (0.00%)  0
Nervous system disorders             
Headache  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/12 (8.33%)  1 0/18 (0.00%)  0 0/18 (0.00%)  0 1/18 (5.56%)  1
Dizziness  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 1/18 (5.56%)  1 0/18 (0.00%)  0 0/18 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Cough  1  5/6 (83.33%)  10 4/6 (66.67%)  4 0/12 (0.00%)  0 1/18 (5.56%)  1 0/18 (0.00%)  0 1/18 (5.56%)  1
Nasopharyngitis  1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/12 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0
Acute sinusitis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0 1/18 (5.56%)  1
Upper respiratory infection  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0 1/18 (5.56%)  1
Skin and subcutaneous tissue disorders             
Erythema  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/12 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0 1/18 (5.56%)  1
Vascular disorders             
Phlebitis  1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/12 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0 0/18 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
MannKind has right to 1st joint multicenter publication. After 1st publication PI may publish data only if PI submits proposed publication to MNKD for review 60 days prior to publication date. MNKD may remove any confidential information. If a multicenter publication is not submitted 12 months after conclusion, abandonment, or termination of the Study at all sites, or if MNKD confirms there will be no multicenter Study publication, PI may publish the Study results subject to MNKD rights herein.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: MannKind Corporation
Phone: 201-983-5000
Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT00570687     History of Changes
Other Study ID Numbers: MKC-TI-118
First Submitted: December 7, 2007
First Posted: December 11, 2007
Results First Submitted: July 22, 2014
Results First Posted: October 16, 2014
Last Update Posted: October 16, 2014