NCT00747006

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at below P25 for phase_2 diabetes-mellitus-type-2

Timeline
Completed

Started Sep 2008

Longer than P75 for phase_2 diabetes-mellitus-type-2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2008

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

September 3, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 4, 2008

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2011

Completed
3.5 years until next milestone

Results Posted

Study results publicly available

October 21, 2014

Completed
Last Updated

October 30, 2014

Status Verified

October 1, 2014

Enrollment Period

2.4 years

First QC Date

September 3, 2008

Results QC Date

July 22, 2014

Last Update Submit

October 21, 2014

Conditions

Diabetes Mellitus, Type 2Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (8)

  • Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects)

    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

    0 to 240 minutes

  • Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects)

    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

    0 to 240 minutes

  • Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)

    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

    0 to 240 minutes

  • Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)

    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

    0 to 240 minutes

  • Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects)

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

    0 to 240 minutes

  • Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects)

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

    0 to 240 minutes

  • Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects)

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

    0 to 240 minutes

  • Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects)

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

    0 to 240 minutes

Secondary Outcomes (4)

  • Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects)

    0 to 240 minutes

  • Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects)

    0 to 240 minutes

  • Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)

    0 to 240 minutes

  • Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)

    0 to 240 minutes

Study Arms (2)

TI Inhalation Powder (original protocol)

EXPERIMENTAL

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)

TI Inhalation Powder and Humalog (Amendment 1)

OTHER

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)

Interventions

TI Inhalation Powder and Humalog (Amendment 1)DRUG

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.

TI Inhalation Powder and Humalog (Amendment 1)
TI Inhalation Powder (original protocol)DRUG

Inhaled insulin technology to be administered immediately before a meal (prandially) for glucose control in Type 1 or Type 2 diabetics

TI Inhalation Powder (original protocol)

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sansum Medical Research Institute

Santa Barbara, California, 93105, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes Mellitus, Type 1

Interventions

Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-ActingInsulinsPancreatic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPeptidesAmino Acids, Peptides, and Proteins

Limitations and Caveats

\- Early termination of trial leading to small numbers of subjects analyzed.

Results Point of Contact

Title
Chief Medical Officer
Organization
MannKind Corporation
aboss@mannkindcorp.com
201-983-5000

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 3, 2008

First Posted

September 4, 2008

Study Start

September 1, 2008

Primary Completion

February 1, 2011

Study Completion

May 1, 2011

Last Updated

October 30, 2014

Results First Posted

October 21, 2014

Record last verified: 2014-10

Locations

US(1)