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

October 9, 2014 updated by: Mannkind Corporation

The original protocol was a randomized, open-label, 3-way cross-over study with 9 scheduled visits. The visits comprised an initial screening visit, 3 treatment visits for the meal challenge followed by a 2-6-week blood-loss recovery period, an interim safety visit, 3 sequential visits for the glucose clamp, and a final close-out visit.

Protocol Amendment 1 was a randomized, open-label, 2-way cross-over study with 7 visits for each completed subject. The visits comprise an initial screening visit, 2 treatment visits for the meal challenge followed by a 2-6-week blood-loss recovery period, an interim safety visit, 2 sequential visits for the glucose clamp, and a final close-out visit.

For both the original protocol and Protocol Amendment 1, subjects were hospitalized in the clinical unit for all procedures.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The original protocol was a randomized, open-label, 3-way cross-over study with 9 scheduled visits. The visits comprised an initial screening visit, 3 treatment visits for the meal challenge followed by a 2-6-week blood-loss recovery period, an interim safety visit, 3 sequential visits for the glucose clamp, and a final close-out visit.

After review of the meal challenge data from the Original Protocol design, it became apparent that the TI Inhalation Powder, insulin lispro, and Exubera doses were not well matched, and resulted in significantly higher insulin exposure following insulin lispro than the two inhaled treatments. All meal challenge visits were completed for the 18 subjects enrolled. However, the glucose clamp visits were discontinued since it was discovered that a direct comparison between the treatments was not possible.

The protocol was amended (Amendment 1) to ensure that the insulin exposures between TI Inhalation Powder and insulin lispro were more suited (increased the TI Inhalation Powder doses and decreased the insulin lispro dose). An Exubera arm was not included in Amendment 1 due to the market removal of this product.

Protocol Amendment 1 was a randomized, open-label, 2-way cross-over study with 7 visits for each completed subject. The visits comprise an initial screening visit, 2 treatment visits for the meal challenge followed by a 2-6-week blood-loss recovery period, an interim safety visit, 2 sequential visits for the glucose clamp, and a final close-out visit.

For both the original protocol and Protocol Amendment 1, subjects were hospitalized in the clinical unit for all procedures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • GER
      • Neuss, GER, Germany
        • Profil Institute for Metabolic Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Receiving diabetes treatment with insulin for a minimum of 3 months
  • Body Mass Index (BMI) of ≤ 34 kg/m2 and ≥ 25 kg/m2
  • HbA1c ≤ 8.5% based upon results from a central laboratory
  • Non-smoking Males and females ≥ 18 and ≤ 70 years of age
  • A clinical diagnosis of type 2 diabetes mellitus for ≥ 12 months

Exclusion Criteria:

  • Total daily insulin requirement of ≥ 1.2 U/kg body weight
  • Use of Symlin® (pramlintide acetate) and/or Byetta® (exenatide) within the preceding 8 weeks
  • Two or more severe hypoglycemic episodes within 6 months of screening
  • Any hospitalization or emergency room visit due to poor diabetic control within 6 months of Screening
  • Severe complications of diabetes
  • Previous exposure to any inhaled insulin product
  • Currently using an insulin delivery pump
  • Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the trial
  • Any clinically important pulmonary disease, confirmed by documented history, pulmonary function testing, or radiologic findings
  • Chronic use of systemic steroids
  • Inability to perform PFT maneuvers to meet the recommended American Thoracic Society (ATS) standards of acceptability and repeatability
  • Significant improvement in spirometry following bronchodilation
  • Active respiratory infection
  • Seizure disorder
  • Significant cardiovascular dysfunction and/or history within 3 months of Screening
  • Uncontrolled hypertension with a systolic blood pressure of >160 mm Hg and/or diastolic blood pressure > 95 mm Hg at screening, despite pharmacologic treatment
  • Clinical nephrotic syndrome or renal dysfunction or disease
  • Cancer (other than an excised cutaneous basal cell carcinoma) within the past 5 years or any history of lung neoplasms
  • History of active viral and/or cirrhotic hepatic disease and/or abnormal liver enzymes
  • Active infection eg, Human Immunodeficiency Virus (HIV), Hepatitis, or history of severe infection within 30 days of Screening
  • Anemia
  • A previous diagnosis of systemic autoimmune or collagen vascular disease requiring prior or current treatment with systemic corticosteroids, cytotoxic drugs or penicillamine
  • Any concurrent illness, other than diabetes mellitus not controlled by a stable therapeutic regime
  • Current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity
  • Clinically significant abnormalities on screening laboratory evaluation
  • Female subjects who are pregnant, lactating or planning to become pregnant during the clinical trial period
  • Female subjects of childbearing potential (defined as pre-menopausal and not surgically sterilized or post-menopausal for less than 2 years) not practicing adequate birth control.
  • Current drug or alcohol abuse, or a history of drug or alcohol abuse, that, in the opinion of the PI, would not make the subject a suitable candidate for participation in the clinical trial
  • Exposure to any investigational medications or devices within the previous 30 days prior to trial entry or participation in another clinical trial during this trial
  • Unable and/or unlikely to comprehend and/or follow the trial protocol
  • Concurrent medical or major psychiatric condition which, in the opinion of the PI, makes the subject unsuitable for the clinical trial, or could limit the validity of the informed consent and/or impair the subject's ability to participate in the trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
Technosphere Insulin
Drug: Technosphere Insulin
Inhalation 15U/30U

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to Minimum Endogenous Glucose Production (EGP) - Meal Challenge
Time Frame: 0-480 minutes
Time to minimum EGP post dose
0-480 minutes
Minimum EGP - Meal Challenge
Time Frame: 0-480 minutes
Minimum calculated EGP per subject as change from baseline
0-480 minutes
EGP AOC0-480 - Meal Challenge
Time Frame: 0-480 minutes
EGP area over the curve from 0 to 480 minutes postdose
0-480 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mannkind Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Klaus Rave, MD, Profil Institute for Metabolic Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 7, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 16, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MKC-TI-118

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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