Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder)When an Optimal Dose is Taken With Varied Carbohydrate Intake

• Sponsor: Mannkind Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00747006
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 31.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if, once a favorable dose of TI Inhalation Powder is established for either a type 1 or 2 patient, based on a average diabetic meal, the patient's favorable dose can be used safely, regardless of change in meal carbohydrate content. Patients were randomly assigned to various carbohydrate loads (0%, 50%, 100%, 150% or 200%). The 100% carbohydrate load was determined based upon their standard insulin dose for their normal meal.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1	Drug: TI Inhalation Powder and Humalog (Amendment 1); Drug: TI Inhalation Powder (original protocol)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Single-Center, Open-Label, Pharmacodynamic Clinical Trial to Evaluate the Effect of Technosphere® Insulin Inhalation Powder Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) on Postprandial Glucose Levels in Subjects With Type 1 and Type 2 Diabetes Mellitus Ingesting Meals With Varied Carbohydrate Content
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TI Inhalation Powder (original protocol) Under the original protocol, subjects with Type 1 and Type 2 diabetes will have TI Inhalation Powder administered prandially during dose optimization visits and meal challenge visits (with meals of varying carbohydrate contents). Subjects with Type 2 diabetes will also use TI Inhalation Powder daily at each meal between visits.	Drug: TI Inhalation Powder (original protocol); Inhaled insulin technology to be administered immediately before a meal (prandially) for glucose control in Type 1 or Type 2 diabetics
Other: TI Inhalation Powder and Humalog (Amendment 1) Under Amendment 1, TI Inhalation Powder will be administered prandially to a new subset of subjects with Type 2 diabetes during TI dose optimization visits and TI meal challenge visits (with meals of varying carbohydrate contents). Subjects will be crossed over to administration of Humalog 15 minutes before meals during Humalog dose optimization visits and Humalog meal challenge visits (with meals of varying carbohydrate contents). Subjects will also use TI Inhalation Powder daily at each meal between visits.	Drug: TI Inhalation Powder and Humalog (Amendment 1); Subcutaneous (sc) rapid acting analog to be administered at one half of the meal challenge visits 15 minutes before a meal. Only the last 5 - 10 patients (Type 2) will be undergoing this amendment to the protocol.

Outcome Measures

Primary Outcome Measures

1. Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects) [0 to 240 minutes]

   AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

2. Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects) [0 to 240 minutes]

   AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

3. Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects) [0 to 240 minutes]

   AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

4. Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects) [0 to 240 minutes]

   AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

5. Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects) [0 to 240 minutes]

   Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch

6. Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects) [0 to 240 minutes]

   Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast

7. Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects) [0 to 240 minutes]

   Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

8. Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects) [0 to 240 minutes]

   Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Secondary Outcome Measures

1. Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects) [0 to 240 minutes]

   Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch

2. Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects) [0 to 240 minutes]

   Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast

3. Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects) [0 to 240 minutes]

   Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

4. Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects) [0 to 240 minutes]

   Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnoses of type 1 or type 2 diabetes mellitus

• Fasting Plasma Glucose (FPG) 80, 140 mg/dL and glycated hemoglobin (A1C) > 6.5% and < or = 10.0%.

• Body mass index (BMI) of < or = 40 kg/m2

• Non-smokers (never smoked or former smokers [= 6 months since cessation]) and a urine cotinine level < or = 100 ng/dL

• Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) Predicted; pre-bronchodilator FEV1 as a percentage of forced vital capacity (FEV1/Forced vital capacity(FVC)) = 70%

• For subjects with type 2 diabetes mellitus: Currently receiving oral diabetic treatment or basal insulin +/- oral diabetic treatment

Exclusion Criteria:

• History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease confirmed by pulmonary function test (PFT) and/or radiologic findings

• Elevated liver function test (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times the normal reference range or bilirubin > 1.5 times the reference range)

• Previous use of Exubera; use of Symlin (pramlintide acetate) and/or Byetta (exenatide) within the past 12 weeks

• Unstable diabetes control and evidence of severe complications of diabetes mellitus (ie, autonomic neuropathy)

• Exposure to any investigational product(s) in the past 12 weeks

• For subjects with type 2 diabetes mellitus: In subjects taking metformin, serum creatinine > 1.4 mg/dL in female subjects and > 1.5 mg/dL in male subjects

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sansum Medical Research Institute	Santa Barbara	California	United States	93105

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: NCT00747006
• Other Study ID Numbers: MKC-TI-119
• First Posted: Sep 4, 2008
• Last Update Posted: Oct 30, 2014
• Last Verified: Oct 1, 2014

• Additional relevant MeSH terms: Respiratory Aspiration; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	Original Protocol Type 1 Diabetes	Original Protocol Type 2 Diabetes	Amendment 1 Type 2 Diabetes
Arm/Group Description	Original protocol participants with Type 1 diabetes given Technosphere Insulin (TI - doses individualized for each patient) at various carbohydrate loads [0%, 50%, 100% (reference), 200%, and if necessary, 150%)	Original protocol participants with Type 2 diabetes given Technosphere Insulin (TI - doses individualized for each patient) at various carbohydrate loads [0%, 50%, 100% (reference), 200%, and if necessary, 150%)	Protocol amendment 1 participants with Type 2 diabetes given humalog (doses individualized for each patient) or Technosphere Insulin (doses individualized for each patient) at various carbohydrate loads [0%, 50%, 100% (reference), 200%, and if necessary, 150%)
Period Title: Overall Study
STARTED	7	8	3
COMPLETED	4	7	2
NOT COMPLETED	3	1	1

Baseline Characteristics

Arm/Group Title	Original Protocol Type 1 Diabetes	Original Protocol Type 2 Diabetes	Amendment 1 Type 2 Diabetes	Total
Arm/Group Description	Original protocol participants with Type 1 diabetes given Technosphere Insulin (TI - doses individualized for each patient) at various carbohydrate loads [0%, 50%, 100% (reference), 200%, and if necessary, 150%)	Original protocol participants with Type 2 diabetes given Technosphere Insulin (TI - doses individualized for each patient) at various carbohydrate loads [0%, 50%, 100% (reference), 200%, and if necessary, 150%)	Protocol amendment 1 participants with Type 2 diabetes given humalog (doses individualized for each patient) or Technosphere Insulin (doses individualized for each patient) at various carbohydrate loads [0%, 50%, 100% (reference), 200%, and if necessary, 150%)	Total of all reporting groups
Overall Participants	7	8	3	18
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	40.7	59.4	50.7	50.7
Sex: Female, Male (Count of Participants)
Female	2 28.6%	1 12.5%	1 33.3%	4 22.2%
Male	5 71.4%	7 87.5%	2 66.7%	14 77.8%

Outcome Measures

1. Primary Outcome

Title	Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects)
Description	AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Original Protocol Type 1 Diabetes Mellitus Technosphere Insulin Treated; 50% carbohydrate load was administered but not completed due to all subjects having hypoglycemia, 0% carbohydrate load was deemed unsafe by PI

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	0	0	3	3
Mean (Full Range) [min*mg/dL]	-41.44	251.65	454.07

2. Primary Outcome

Title	Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects)
Description	AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Original Protocol Type 1 Diabetes Mellitus Technosphere Insulin Treated; 0% carbohydrate load was deemed unsafe by PI

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	0	3	2	3
Mean (Full Range) [min*mg/dL]	104.32	10.80	199.35	440.90

3. Primary Outcome

Title	Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)
Description	AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Protocol Amendment 1 Type 2 Diabetes Mellitus Technosphere Insulin Treated Subjects; 150% carbohydrate load was not done per protocol since the 200% carbohydrate load was administered

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	2	1	0	2
Mean (Full Range) [min*mg/dL]	-6.11	-74.26	-22.80	11.56

4. Primary Outcome

Title	Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)
Description	AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Protocol Amendment 1 Type 2 Diabetes Mellitus Humalog Treated Subjects; 150% carbohydrate load was not done per protocol since the 200% carbohydrate load was administered

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	2	2	0	2
Mean (Full Range) [min*mg/dL]	15.77	-51.26	4.18	-8.15

5. Primary Outcome

Title	Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects)
Description	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Original Protocol Type 1 Diabetes Mellitus Technosphere Insulin Treated; 50% carbohydrate load was administered but not completed due to all subjects having hypoglycemia, 0% carbohydrate load was deemed unsafe by PI

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	0	0	3	3
Mean (Full Range) [mg/dL]	54.00	129.67	201.00

6. Primary Outcome

Title	Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects)
Description	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Original Protocol Type 1 Diabetes Mellitus Technosphere Insulin Treated; 0% carbohydrate load was deemed unsafe by PI

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	0	3	2	3
Mean (Full Range) [mg/dL]	53.50	44.33	89.50	186.33

7. Primary Outcome

Title	Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects)
Description	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Protocol Amendment 1 Type 2 Diabetes Mellitus TI Treated Subjects; 150% carbohydrate load was not done per protocol since the 200% carbohydrate load was administered

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	2	1	0	2
Mean (Full Range) [mg/dL]	29.50	14.50	16.00	18.50

8. Primary Outcome

Title	Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects)
Description	Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Protocol Amendment 1 Type 2 Diabetes Mellitus Humalog Treated Subjects; 150% carbohydrate load was not done per protocol since the 200% carbohydrate load was administered

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	2	2	0	2
Mean (Full Range) [mg/dL]	44.50	20.00	23.50	45.50

9. Secondary Outcome

Title	Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects)
Description	Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Original Protocol Type 1 Diabetes Mellitus Technosphere Insulin Treated; 50% carbohydrate load was administered but not completed due to all subjects having hypoglycemia, 0% carbohydrate load was deemed unsafe by PI

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	0	0	3	3
Mean (Full Range) [min*mg/dL]	53.89	19.16	8.77

10. Secondary Outcome

Title	Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects)
Description	Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Original Protocol Type 1 Diabetes Mellitus Technosphere Insulin Treated; 0% carbohydrate load was deemed unsafe by PI

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	0	3	2	3
Mean (Full Range) [min*mg/dL]	10.25	30.45	6.30	3.18

11. Secondary Outcome

Title	Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)
Description	Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Protocol Amendment 1 Type 2 Diabetes Mellitus Technosphere Insulin Treated Subjects; 150% carbohydrate load was not done per protocol since the 200% carbohydrate load was administered

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	2	1	0	2
Mean (Full Range) [min*mg/dL]	18.00	74.26	24.04	5.65

12. Secondary Outcome

Title	Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)
Description	Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch
Time Frame	0 to 240 minutes

Outcome Measure Data

Analysis Population Description

Protocol Amendment 1 Type 2 Diabetes Mellitus Humalog Treated Subjects; 150% carbohydrate load was not done per protocol since the 200% carbohydrate load was administered

Arm/Group Title	100% Carbohydrate Load	0% Carbohydrate Load	50% Carbohydrate Load	150% Carbohydrate Load	200% Carbohydrate Load
Arm/Group Description	Standard meal to which subjects titrated their insulin dose.	Fasting state	Meal consisting of half of the carbohydrates from the standard meal	Meal consisting of 1.5 times the carbohydrate load of the standard meal.	Meal consisting of 2 times the carbohydrate load of the standard meal.
Measure Participants	2	2	2	0	2
Mean (Full Range) [min*mg/dL]	14.60	51.63	12.52	40.84

Adverse Events

Arm/Group Title	TI Original Protocol Type 1 DM		TI Original Protocol Type 2 DM		TI Amendment 1 Type 2 DM		Humalog Amendment 1 Type 2 DM
Arm/Group Description	Original protocol type 1 diabetes mellitus subjects		Original protocol type 2 diabetes mellitus subjects		Technosphere Insulin treated subjects in protocol amendment 1		Humalog treated subjects in protocol amendment 1
All Cause Mortality
	TI Original Protocol Type 1 DM		TI Original Protocol Type 2 DM		TI Amendment 1 Type 2 DM		Humalog Amendment 1 Type 2 DM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	TI Original Protocol Type 1 DM		TI Original Protocol Type 2 DM		TI Amendment 1 Type 2 DM		Humalog Amendment 1 Type 2 DM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		3/8 (37.5%)		0/3 (0%)		0/2 (0%)
Cardiac disorders
Sinus bradycardia	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Renal and urinary disorders
Renal papillary necrosis	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	TI Original Protocol Type 1 DM		TI Original Protocol Type 2 DM		TI Amendment 1 Type 2 DM		Humalog Amendment 1 Type 2 DM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		7/8 (87.5%)		3/3 (100%)		1/2 (50%)
Gastrointestinal disorders
Abdominal pain	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
General disorders
Venipuncture site thrombosis	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Immune system disorders
Allergy to plants	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Infections and infestations
Nasopharyngitis	0/7 (0%)		0/8 (0%)		1/3 (33.3%)		0/2 (0%)
Influenza	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Sinusitis	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Tooth abscess	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Upper respiratory tract infection	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Urinary tract infection	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Investigations
Blood creatine phosphokinase increased	0/7 (0%)		0/8 (0%)		1/3 (33.3%)		0/2 (0%)
Forced expiratory volume decreased	0/7 (0%)		0/8 (0%)		0/3 (0%)		1/2 (50%)
Platelet count increased	0/7 (0%)		0/8 (0%)		0/3 (0%)		1/2 (50%)
Metabolism and nutrition disorders
Hypoglycaemia	7/7 (100%)		6/8 (75%)		2/3 (66.7%)		1/2 (50%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Nervous system disorders
Headache	1/7 (14.3%)		0/8 (0%)		1/3 (33.3%)		0/2 (0%)
Hypoaesthesia	0/7 (0%)		0/8 (0%)		1/3 (33.3%)		0/2 (0%)
Dizziness postural	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Reproductive system and breast disorders
Erectile dysfunction	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	0/7 (0%)		1/8 (12.5%)		1/3 (33.3%)		0/2 (0%)
Nasal congestion	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Snoring	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Ingrowing nail	1/7 (14.3%)		0/8 (0%)		0/3 (0%)		0/2 (0%)
Vascular disorders
Thrombophlebitis	0/7 (0%)		1/8 (12.5%)		0/3 (0%)		0/2 (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.