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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Amendment 1: TI 60 U Then Insulin Lispro 10 U 60 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, followed by 10 U subcutaneously administered insulin lispro
Amendment 1: 10 U Insulin Lispro Then 60 U TI 10 U subcutaneously administered insulin lispro, followed by 60 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler
Amendment 1: TI 90 U Then 10 U Insulin Lispro 90 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler, followed by 10 U subcutaneously administered insulin lispro
Amendment 1: 10 U Insulin Lispro Then 90 U TI 10 U subcutaneously administered insulin lispro, followed by 90 U of Technosphere Insulin (TI) administered via inhalation using MedTone inhaler
Original Protocol: TI to Insulin Lispro to Exubera 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
Original Protocol: TI to Exubera to Insulin Lispro 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
Original Protocol: Exubera to Insulin Lispro to TI 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
Original Protocol: Exubera to TI to Insulin Lispro 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
Original Protocol: Insulin Lispro to TI to Exubera 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
Original Protocol: Insulin Lispro to Exubera to TI 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

Participant Flow for 17 periods

Period 1:   Meal Challenge 1 (1 Day) - Orig Protocol
    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
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 2:   Washout 1 (7-21 Days) - Orig Protocol
    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
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 3:   Meal Challenge 2 (1 Day) - Orig Protocol
    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
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 4:   Washout 2 (7-21 Days) - Orig Protocol
    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
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 5:   Meal Challenge 3 (1 Day) - Orig Protocol
    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
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 6:   Washout 3 (7-21 Days) - Orig Protocol
    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
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 
Sponsor Decision                0                0                0                0                3                3                2                3                2                3 

Period 7:   Clamp 1 (1 Day) - Orig Protocol
    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
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 8:   Washout 4 (7-21 Days) - Orig Protocol
    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
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 
Sponsor Decision                0                0                0                0                0                0                0                0                1                0 

Period 9:   Clamp 2 (1 Day) - Orig Protocol
    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
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 10:   Washout 5 (7-21 Days) - Orig Protocol
    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
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 
Sponsor Decision                0                0                0                0                0                0                1                0                0                0 

Period 11:   Meal Challenge 1 (1 Day) - Amendment 1
    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
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 12:   Washout 1 (7-21 Days) - Amendment 1
    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
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 13:   Meal Challenge 2 (1 Day) - Amendment 1
    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
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 14:   Washout 2 (8 Weeks) - Amendment 1
    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
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 15:   Clamp 1 (1 Day) - Amendment 1
    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
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 16:   Washout 3 (7-21 Days) - Amendment 1
    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
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 17:   Clamp 2 (1 Day) - Amendment 1
    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
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 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Amendment 1 2-way crossover study of 60 U or 90 U of Technosphere Insulin Inhalation Powder crossed with 10 U of subcutaneous insulin lispro
Original Protocol 3-way crossover study of 45 U of Technosphere Insulin Inhalation Powder, 4 mg of Exubera, and 12 U of subcutaneous insulin lispro
Total Total of all reporting groups

Baseline Measures
   Amendment 1   Original Protocol   Total 
Overall Participants Analyzed 
[Units: Participants]
 12   18   30 
Age 
[Units: Years]
Mean (Standard Deviation)
 55.3  (7.6)   54.9  (6.9)   55.1  (7.2) 
Gender 
[Units: Participants]
     
Female   3   3   6 
Male   9   15   24 


  Outcome Measures

1.  Primary:   Time to Minimum Endogenous Glucose Production (EGP) - Meal Challenge   [ Time Frame: 0-480 minutes ]

2.  Primary:   Minimum EGP - Meal Challenge   [ Time Frame: 0-480 minutes ]

3.  Primary:   EGP AOC0-480 - Meal Challenge   [ Time Frame: 0-480 minutes ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: MannKind Corporation
phone: 201-983-5000
e-mail: aboss@mannkindcorp.com



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