Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Inhalation Insulin (TI) Inhalation Powder Using the Gen2 Inhaler
Sponsor
Mannkind Corporation (Industry)
Overall Status
Terminated
CT.gov ID
NCT01196104
Collaborator
(none)
39
29
2
18
1.3
0.1
Study Details
Study Description
Brief Summary
This is an open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of Technosphere Insulin (TI) Inhalation Powder in combination with insulin glargine versus insulin aspart in combination with insulin glargine in subjects with type 2 diabetes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Phase 3 clinical trial is designed to examine the efficacy and safety of inhaled prandial TI Inhalation Powder in combination with basal insulin verses insulin aspart in combination with basal insulin in subjects with type 2 diabetes who are suboptimally controlled with their current insulin regimens.This trial will employ a variety of methods to intensively manage these subjects.
Study Design
Study Type:
Interventional
Actual Enrollment
:
39 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3b, Multicenter, Open-label, Randomized, Forced-titration Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder, Using the Gen2 Inhaler, in Combination With Insulin Glargine Versus Insulin Aspart in Combination With Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Over a 16-week Treatment Period
Study Start Date
:
Sep 1, 2010
Actual Primary Completion Date
:
Aug 1, 2011
Actual Study Completion Date
:
Mar 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Technosphere® Insulin Inhalation Powder (TI) Insulin Glargine and Technosphere® Insulin Inhalation Powder |
Drug: Technosphere® Insulin Inhalation Powder
Drug: Insulin Glargine
|
| Active Comparator: Comparator Insulin Glargine and Insulin Aspart |
Drug: Insulin Aspart
Usual Care
Drug: Insulin Glargine
|
Outcome Measures
Primary Outcome Measures
- Change in HbA1c (%) From Baseline to Week 16 [Baseline to Week 16]
Change from Baseline in glycated hemoglobin at Week 16
Secondary Outcome Measures
- To Evaluate the Effect of Each Treatment on HbA1c [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Comparison of Fasting Plasma Glucose (FPG) Levels at Randomization and Throughout the Study [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Comparison of Post-prandial Glucose (PPG) Levels at Randomization and Throughout the Study [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Glycomark and Fructosamine Levels Measured Throughout the Study [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Seven-point Glucose at Randomization and Throughout the Study [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Glycemic Excursions and Variability as Assessed Through Continuous Glucose Monitoring (CGM) [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Changes in Body Weight at 16 Weeks [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Treatment Satisfaction as Assessed by Subject Treatment and Health Outcomes Questionnaires [Change from baseline to 16 weeks]
Not analyzed due to early termination of the trial.
- Total Number of Cough Episodes [Baseline to Week 16]
Total number of times patients coughed once, intermittently or continuously (inclusive)
- Severe Hypoglycemic Event Rate [Baseline to Week 16]
Severe hypoglycemic event rate, ie, total number of events divided by subject-months of observation Severe hypoglycemia is defined as a subject who requires the assistance of another individual (not merely requested) and either: SMBG levels ≤ 36 mg/dL OR There is a prompt response to the administration of carbohydrate, glucagon, or other resuscitative measures
- Mild or Moderate Hypoglycemic Event Rate [Baseline to Week 16]
Mild or moderate hypoglycemic event rate, ie, total number of events divided by subject-months of observation Nonsevere hypoglycemia is defined as a subject: SMBG levels < 70 mg/dL AND/OR Symptoms that are relieved by the self-administration of carbohydrates
- Number of Subjects Reporting Cough Episodes [Baseline to Week 16]
Number of Subjects Reporting Cough Episodes
- Number of Subjects Reporting Intermittent Coughing Episodes [Baseline to Week 16]
Number of subjects reporting Intermittent Coughing Episodes
- Number of Single Coughing Episodes [Baseline to Week 16]
Total number of times patients coughed only once
- Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation [Baseline to Week 16]
- Baseline Forced Expiratory Volume in 1 Second (FEV1) [Baseline]
Baseline FEV1
- Week 16 Forced Expiratory Volume in 1 Second [Week 16]
Week 16 FEV1
- Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second [Baseline to Week 16]
Week 16 Change from Baseline in FEV1
- Week 20 (Follow-up) Forced Expiratory Volume in 1 Second [Week 20 (Follow-up)]
Week 20 (Follow-up) FEV1, 4 weeks after discontinuation of study treatment
- Week 20 (Follow-up) Change From Baseline in Forced Expiratory Volume in 1 Second [Baseline to Week 20]
Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FEV1
- Baseline Forced Vital Capacity (FVC) [Baseline]
Baseline FVC
- Week 16 Forced Vital Capacity [Week 16]
Week 16 FVC
- Week 16 Change From Baseline Forced Vital Capacity [Baseline to Week 16]
Week 16 Change from Baseline FVC
- Week 20 (Follow-up) Forced Vital Capacity [Week 20]
Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) FVC
- Week 20 (Follow-up) Change From Baseline in Forced Vital Capacity [Baseline to Week 20]
Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FVC
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Men and women ≥ 18 and ≤ 80 years of age
-
Clinical diagnosis of type 2 diabetes mellitus for more than 12 months
-
Body mass index (BMI) ≤ 45 kg/m2
-
Glycated Hemoglobin (HbA1c) > 6.5% and ≤ 10.0%
-
Treatment with 1 to 3 Oral Antidiabetic Drugs (OADs) and basal insulin for a minimum of 3 months before screening. Doses of OADs must have been stable for 3 months before study entry
-
Nonsmokers (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding ≥ 6 months
-
Office spirometry at the investigator site
-
Forced expiratory volume in 1 second (FEV1) ≥ 65% Third National Health and Nutrition Examination Survey (NHANES III) predicted
-
Forced vital capacity (FVC) ≥ 65% NHANES III predicted
-
Forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1/FVC) ≥ lower limit of normal (LLN)
Exclusion criteria:
-
Current or prior treatment with prandial or PreMix (70/30) insulin
-
History of insulin pump use within 6 weeks of Visit 1
-
Treatment with Glucagon-like Peptide (GLP-1) analog drugs within the preceding 12 weeks of Visit 1
-
History of chronic obstructive pulmonary disease (COPD), asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis)
-
Any clinically significant radiological findings on screening chest x-ray
-
Use of medications for asthma, COPD, or any other chronic respiratory conditions
-
Evidence of serious complications of diabetes (eg, symptomatic autonomic neuropathy)
-
Significant cardiovascular dysfunction or history within 3 months of Visit 1 (eg, congestive heart failure [New York Heart Association Class III or IV])
-
Serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or any cerebrovascular accident
-
History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening (Visit 1)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Coastal Clinical Research Inc | Mobile | Alabama | United States | 36608 |
| 2 | Valley Research | Fresno | California | United States | 93720 |
| 3 | Health Care Partners Medical Group | Long Beach | California | United States | 90806 |
| 4 | Diabetes Research Center | Tustin | California | United States | 92780 |
| 5 | Diablo Clinical Research | Walnut Creek | California | United States | 94598 |
| 6 | Laureate Clinical Research Group | Atlanta | Georgia | United States | 30308 |
| 7 | Atlanta Diabetes Associates | Atlanta | Georgia | United States | 30309 |
| 8 | Alta Pharmaceutical Research Center | Dunwoody | Georgia | United States | 30338 |
| 9 | John H Stoger Jr Hospital of Cook County | Chicago | Illinois | United States | 60612 |
| 10 | LaPorte County Institute for Clinical Research Inc. | Michigan City | Indiana | United States | 46360 |
| 11 | Radiant Research Inc (Minneapolis) | Edina | Minnesota | United States | 55435 |
| 12 | Amin Radparvar's Private Practice | St Peters | Missouri | United States | 63376 |
| 13 | Washington University School of Medicine | St. Louis | Missouri | United States | 63110 |
| 14 | Billings Clinic Research Center | Billings | Montana | United States | 59101 |
| 15 | Creighton Diabetes Center | Omaha | Nebraska | United States | 68131 |
| 16 | University of New Mexico HCS | Albuquerque | New Mexico | United States | 87131 |
| 17 | Winthrop University Hospital | Mineola | New York | United States | 11501 |
| 18 | North Shore Diabetes and Endocrine Associates | New Hyde Park | New York | United States | 11042 |
| 19 | Endocrine Research Physicians East PA | Greenville | North Carolina | United States | 27834 |
| 20 | Your Diabetes Endocrine Nutrition Group, Inc. | Mentor | Ohio | United States | 44060 |
| 21 | Legacy Clinical Research | Portland | Oregon | United States | 97232 |
| 22 | OHSU Diabetes Center Research Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 23 | The Endocrine Clinic | Memphis | Tennessee | United States | 38119 |
| 24 | Dallas Diabetes & Endocrine Center | Dallas | Texas | United States | 75230 |
| 25 | Baylor Endocrine Center | Dallas | Texas | United States | 75246 |
| 26 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 27 | SAM Clinical Research Center | San Antonio | Texas | United States | 78229 |
| 28 | Exodus Healthcare Network | Magna | Utah | United States | 84044 |
| 29 | Diabetes Research Center -Fletcher Allen Health Care | South Burlington | Vermont | United States | 05403 |
Sponsors and Collaborators
- Mannkind Corporation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT01196104
Other Study ID Numbers:
- MKC-TI-162
First Posted:
Sep 8, 2010
Last Update Posted:
Oct 30, 2014
Last Verified:
Oct 1, 2014
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The FIrst Patient First Visit (FPFV) was September 21, 2010, and Last Patient Last Visit (LPLV) was August 25, 2011. Trial conducted in US. The study was terminated before completion of full enrollment for business reasons. Subjects already enrolled were allowed to complete the study to assess the safety of the titration algorithms. |
|---|---|
| Pre-assignment Detail | After a 1 week to 5 week run-in period, subjects were randomized to receive either TI Inhalation Powder in combination with insulin glargine, or insulin aspart in combination with insulin glargine. 105 Screened/46 Eligible. 39 subjects were randomized; 59 screen failures and 7 were screened but not randomized. |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Period Title: Overall Study | ||
| STARTED | 19 | 20 |
| COMPLETED | 15 | 15 |
| NOT COMPLETED | 4 | 5 |
Baseline Characteristics
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine | Total |
|---|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient | Total of all reporting groups |
| Overall Participants | 19 | 18 | 37 |
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
60.6
(7.95)
|
58.1
(10.67)
|
59.4
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
8
42.1%
|
4
22.2%
|
12
32.4%
|
| Male |
11
57.9%
|
14
77.8%
|
25
67.6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
3
16.7%
|
3
8.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
5.6%
|
1
2.7%
|
| Black or African American |
4
21.1%
|
3
16.7%
|
7
18.9%
|
| White |
15
78.9%
|
11
61.1%
|
26
70.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
19
100%
|
18
100%
|
37
100%
|
| Duration of Diabetes (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
14.6
(7.95)
|
15.6
(10.67)
|
15.1
|
| Body Weight (kg) [Mean (Full Range) ] | |||
| Mean (Full Range) [kg] |
100.9
(21.84)
|
100.8
(20.30)
|
100.9
|
| Body Mass Index (kg/m2) [Mean (Full Range) ] | |||
| Mean (Full Range) [kg/m2] |
33.2
(5.78)
|
33.3
(5.51)
|
33.2
|
| HbA1c (%) [Mean (Full Range) ] | |||
| Mean (Full Range) [%] |
7.76
(1.097)
|
7.94
(1.098)
|
7.85
|
Outcome Measures
| Title | Change in HbA1c (%) From Baseline to Week 16 |
|---|---|
| Description | Change from Baseline in glycated hemoglobin at Week 16 |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, participants with data available at Baseline and Week 16 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 16 | 14 |
| Least Squares Mean (Standard Deviation) [Percentage of total hemoglobin] |
-1.2179
(0.1468)
|
-1.2652
(0.1571)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Comments | ANCOVA model with terms of treatment as a fixed effect and baseline HbA1c as covariate | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Study terminated early due to business reasons, results are not properly powered. | |
| Statistical Test of Hypothesis | p-Value | 0.8283 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.0473 | |
| Confidence Interval |
(2-Sided) 95% -0.4901 to 0.3956 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2158 |
|
| Estimation Comments | ||
| Title | To Evaluate the Effect of Each Treatment on HbA1c |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Comparison of Fasting Plasma Glucose (FPG) Levels at Randomization and Throughout the Study |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Comparison of Post-prandial Glucose (PPG) Levels at Randomization and Throughout the Study |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Glycomark and Fructosamine Levels Measured Throughout the Study |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Seven-point Glucose at Randomization and Throughout the Study |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Glycemic Excursions and Variability as Assessed Through Continuous Glucose Monitoring (CGM) |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Changes in Body Weight at 16 Weeks |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Treatment Satisfaction as Assessed by Subject Treatment and Health Outcomes Questionnaires |
|---|---|
| Description | Not analyzed due to early termination of the trial. |
| Time Frame | Change from baseline to 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Total Number of Cough Episodes |
|---|---|
| Description | Total number of times patients coughed once, intermittently or continuously (inclusive) |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Number [Cough episodes] |
5
|
0
|
| Title | Severe Hypoglycemic Event Rate |
|---|---|
| Description | Severe hypoglycemic event rate, ie, total number of events divided by subject-months of observation Severe hypoglycemia is defined as a subject who requires the assistance of another individual (not merely requested) and either: SMBG levels ≤ 36 mg/dL OR There is a prompt response to the administration of carbohydrate, glucagon, or other resuscitative measures |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Number [Events / subject-month] |
0.01
|
0.34
|
| Title | Mild or Moderate Hypoglycemic Event Rate |
|---|---|
| Description | Mild or moderate hypoglycemic event rate, ie, total number of events divided by subject-months of observation Nonsevere hypoglycemia is defined as a subject: SMBG levels < 70 mg/dL AND/OR Symptoms that are relieved by the self-administration of carbohydrates |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere® Insulin Inhalation Powder (TI) | Comparator |
|---|---|---|
| Arm/Group Description | Insulin Glargine and Technosphere® Insulin Inhalation Powder Technosphere® Insulin Inhalation Powder Insulin Glargine | Insulin Glargine and Insulin Aspart Insulin Aspart: Usual Care Insulin Glargine |
| Measure Participants | 19 | 18 |
| Number [Events / subject-month] |
4.47
|
4.41
|
| Title | Number of Subjects Reporting Cough Episodes |
|---|---|
| Description | Number of Subjects Reporting Cough Episodes |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Number [Number of participants] |
4
21.1%
|
0
0%
|
| Title | Number of Subjects Reporting Intermittent Coughing Episodes |
|---|---|
| Description | Number of subjects reporting Intermittent Coughing Episodes |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Number [Number of participants] |
4
21.1%
|
0
0%
|
| Title | Number of Single Coughing Episodes |
|---|---|
| Description | Total number of times patients coughed only once |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Number [Cough episodes] |
1
|
0
|
| Title | Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation |
|---|---|
| Description | |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Number [Cough episodes] |
5
|
0
|
| Title | Baseline Forced Expiratory Volume in 1 Second (FEV1) |
|---|---|
| Description | Baseline FEV1 |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Mean (Standard Deviation) [L] |
2.97
(0.63)
|
2.83
(0.75)
|
| Title | Week 16 Forced Expiratory Volume in 1 Second |
|---|---|
| Description | Week 16 FEV1 |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 16 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 14 | 15 |
| Mean (Standard Deviation) [L] |
2.91
(0.57)
|
2.66
(0.70)
|
| Title | Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second |
|---|---|
| Description | Week 16 Change from Baseline in FEV1 |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 16 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 14 | 15 |
| Mean (Standard Deviation) [L] |
-0.14
(0.32)
|
-0.07
(0.27)
|
| Title | Week 20 (Follow-up) Forced Expiratory Volume in 1 Second |
|---|---|
| Description | Week 20 (Follow-up) FEV1, 4 weeks after discontinuation of study treatment |
| Time Frame | Week 20 (Follow-up) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 20 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 13 | 14 |
| Mean (Standard Deviation) [L] |
3.07
(0.55)
|
2.86
(0.70)
|
| Title | Week 20 (Follow-up) Change From Baseline in Forced Expiratory Volume in 1 Second |
|---|---|
| Description | Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FEV1 |
| Time Frame | Baseline to Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 20 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 13 | 14 |
| Mean (Standard Deviation) [L] |
-0.07
(0.29)
|
-0.05
(0.28)
|
| Title | Baseline Forced Vital Capacity (FVC) |
|---|---|
| Description | Baseline FVC |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 19 | 18 |
| Mean (Standard Deviation) [L] |
3.63
(0.78)
|
3.48
(1.02)
|
| Title | Week 16 Forced Vital Capacity |
|---|---|
| Description | Week 16 FVC |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 16 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 14 | 15 |
| Mean (Standard Deviation) [L] |
3.61
(0.72)
|
3.33
(0.98)
|
| Title | Week 16 Change From Baseline Forced Vital Capacity |
|---|---|
| Description | Week 16 Change from Baseline FVC |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 16 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 14 | 15 |
| Mean (Standard Deviation) [L] |
-0.13
(0.34)
|
-0.07
(0.36)
|
| Title | Week 20 (Follow-up) Forced Vital Capacity |
|---|---|
| Description | Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) FVC |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 20 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 13 | 14 |
| Mean (Standard Deviation) [L] |
3.77
(0.73)
|
3.57
(0.96)
|
| Title | Week 20 (Follow-up) Change From Baseline in Forced Vital Capacity |
|---|---|
| Description | Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FVC |
| Time Frame | Baseline to Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population, with data available at Week 20 |
| Arm/Group Title | Technosphere Insulin + Insulin Glargine | Insulin Aspart + Insulin Glargine |
|---|---|---|
| Arm/Group Description | Technosphere Insulin Inhalation Powder (administered prior to each meal) in combination with insulin glargine (once or twice daily); doses individualized for each patient | Insulin Aspart (prior to each meal) and Insulin Glargine (once or twice daily) ; doses individualized for each patient |
| Measure Participants | 13 | 14 |
| Mean (Standard Deviation) [L] |
-0.05
(0.35)
|
-0.06
(0.38)
|
Adverse Events
| Time Frame | From first dose to 30d post last dose | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Technosphere® Insulin Inhalation Powder (TI) | Comparator | ||
| Arm/Group Description | Insulin Glargine and Technosphere® Insulin Inhalation Powder Technosphere® Insulin Inhalation Powder Insulin Glargine | Insulin Glargine and Insulin Aspart Insulin Aspart: Usual Care Insulin Glargine | ||
All Cause Mortality |
||||
| Technosphere® Insulin Inhalation Powder (TI) | Comparator | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Technosphere® Insulin Inhalation Powder (TI) | Comparator | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/19 (5.3%) | 1/18 (5.6%) | ||
| Cardiac disorders | ||||
| Angina unstable | 0/19 (0%) | 1/18 (5.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Rib Fracture | 1/19 (5.3%) | 0/18 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Technosphere® Insulin Inhalation Powder (TI) | Comparator | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/19 (68.4%) | 11/18 (61.1%) | ||
| Cardiac disorders | ||||
| Angina Pectoris | 1/19 (5.3%) | 0/18 (0%) | ||
| Atrial Fibrillation | 0/19 (0%) | 1/18 (5.6%) | ||
| Ventricular extrasystoles | 0/19 (0%) | 1/18 (5.6%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 1/19 (5.3%) | 0/18 (0%) | ||
| Eye disorders | ||||
| Mydriasis | 0/19 (0%) | 1/18 (5.6%) | ||
| Vitreous haemorrhage | 0/19 (0%) | 1/18 (5.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain upper | 0/19 (0%) | 1/18 (5.6%) | ||
| Diarrhea | 0/19 (0%) | 1/18 (5.6%) | ||
| General disorders | ||||
| Oedema | 0/19 (0%) | 1/18 (5.6%) | ||
| Oedema Peripheral | 0/19 (0%) | 1/18 (5.6%) | ||
| Infections and infestations | ||||
| Upper Respiratory Tract Infection | 4/19 (21.1%) | 1/18 (5.6%) | ||
| Ear Infection | 1/19 (5.3%) | 0/18 (0%) | ||
| Onychomycosis | 1/19 (5.3%) | 0/18 (0%) | ||
| Sinusitis | 1/19 (5.3%) | 0/18 (0%) | ||
| Urinary Tract Infection | 1/19 (5.3%) | 0/18 (0%) | ||
| Nasopharyngitis | 0/19 (0%) | 1/18 (5.6%) | ||
| Pharyngitis | 0/19 (0%) | 1/18 (5.6%) | ||
| Investigations | ||||
| Blood Testosterone Decreased | 1/19 (5.3%) | 0/18 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/19 (10.5%) | 2/18 (11.1%) | ||
| Back Pain | 1/19 (5.3%) | 0/18 (0%) | ||
| Chest Wall Pain | 0/19 (0%) | 1/18 (5.6%) | ||
| Plantar Fasciitis | 0/19 (0%) | 1/18 (5.6%) | ||
| Nervous system disorders | ||||
| Dizziness | 0/19 (0%) | 1/18 (5.6%) | ||
| Headache | 0/19 (0%) | 1/18 (5.6%) | ||
| Hypoaesthesia | 0/19 (0%) | 1/18 (5.6%) | ||
| Psychiatric disorders | ||||
| Depression | 0/19 (0%) | 1/18 (5.6%) | ||
| Renal and urinary disorders | ||||
| Renal Failure | 0/19 (0%) | 1/18 (5.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 4/19 (21.1%) | 0/18 (0%) | ||
| Sinus Congestion | 1/19 (5.3%) | 0/18 (0%) | ||
| Throat Irritation | 1/19 (5.3%) | 0/18 (0%) | ||
| Dry Throat | 0/19 (0%) | 1/18 (5.6%) | ||
| Dyspnoea | 0/19 (0%) | 1/18 (5.6%) | ||
| Productive Cough | 0/19 (0%) | 1/18 (5.6%) | ||
| Respiratory Tract Congestion | 0/19 (0%) | 1/18 (5.6%) | ||
| Wheezing | 0/19 (0%) | 1/18 (5.6%) | ||
| Surgical and medical procedures | ||||
| Cataract Operation | 0/19 (0%) | 1/18 (5.6%) | ||
| Vascular disorders | ||||
| Hypertension | 1/19 (5.3%) | 0/18 (0%) | ||
Limitations/Caveats
- Early termination of trial leading to small numbers of subjects analyzed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| aboss@mannkindcorp.com |
Responsible Party:
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT01196104
Other Study ID Numbers:
- MKC-TI-162
First Posted:
Sep 8, 2010
Last Update Posted:
Oct 30, 2014
Last Verified:
Oct 1, 2014