Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation
ClinicalTrials.gov Identifier:
NCT01445951
First received: September 30, 2011
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

Open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of TI Inhalation Power in combination with a basal insulin versus insulin aspart in combination with a basal insulin


Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: Technosphere® Insulin with MedTone C Inhaler
Drug: Technosphere ®Insulin with Gen2 Inhaler
Drug: Insulin Aspart in combination with a basal insulin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Open-label, Randomized, Forced-titration Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder in Combination With a Basal Insulin Versus Insulin Aspart in Combination With a Basal Insulin in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period

Resource links provided by NLM:


Further study details as provided by Mannkind Corporation:

Primary Outcome Measures:
  • Change From Baseline to Week 24 in HbA1c [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Effect of treatment as measured by change from baseline in glycated hemoglobin (HbA1c). Primary treatment difference is TI-Gen2 vs. Insulin Aspart at Week 24


Secondary Outcome Measures:
  • FEV1 Change From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Forced Expiratory Volume in 1 second - change from baseline to week 24

  • FPG Change From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Comparison of mean change from Baseline to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results)

  • Mean 7-point Glucose Baseline Values [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Mean 7-point glucose at baseline

  • Mean 7-point Glucose Week 24 Values [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change in Body Weight From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Change in body weight from Baseline to Week 24

  • Proportion of Responders Achieving HbA1c <= 7.0% [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%


Other Outcome Measures:
  • Incidence of Total Hypoglycemia [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.

  • Incidence of Severe Hypoglycemia [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Severe Hypoglycemia defined as: Requiring 3rd party assistance.

  • Total Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Number of Hypoglycemic Events/Total Subject Exposure Time (in months)

  • Severe Hypoglycemia Event Rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
    Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)


Enrollment: 518
Study Start Date: September 2011
Study Completion Date: June 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Technosphere® Insulin with MedTone C Inhaler
Subjects will receive TI with the MedToneC inhaler and remain on the basal insulin they were taking prior to study entry
Drug: Technosphere® Insulin with MedTone C Inhaler
Inhalation Powder and injectable insulin
Active Comparator: Aspart Group
Subjects will receive insulin aspart and remain on the basal insulin they were taking prior to study entry
Drug: Insulin Aspart in combination with a basal insulin
Injectable insulin
Experimental: Technosphere ® Insulin-Gen2 Group
Subject will receive Technosphere Insulin with Gen2 Inhaler and remain on the basal insulin they were taking prior to study entry
Drug: Technosphere ®Insulin with Gen2 Inhaler
Inhalation Powder and injectable insulin

Detailed Description:

Phase 3 clinical trial designed to examine the efficacy and safety of inhaled prandial TI Inhalation Power in combination with basal insulin versus insulin aspart in combination with basal insulin in subjects with type 1 diabetes who are suboptimally controlled with their current insulin regimens. This trial will employ a variety of methods to intensively manage these subjects.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women = 18 years of age
  • Clinical diagnosis of type 1 diabetes mellitus for at least 12 months
  • Body mass index (BMI) = 38 kg/m2
  • Stable dose of basal/bolus insulin therapy for at least 3 months with an FPG consistently < 220 mg/dL:
  • HbA1c = 7.5% and = 10.0%
  • Fasting C-peptide = 0.30 pmol/mL
  • Subject willingness to not use CGM during the entire course of the trial
  • Nonsmoking (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding 6 months
  • Negative urine cotinine test, defined as = 100 ng/mL
  • Lung function tests: • Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted
  • Written informed consent

Exclusion Criteria:

  • Total daily insulin dose = 2 IU/kg/day. History of insulin pump use within 3 months of Screening or use of continuous glucose monitoring within 6 weeks of Screening
  • History of inhaled insulin use in the previous 6 months
  • Two or more unexplained severe hypoglycemic episodes within 3 months of Screening or an episode of severe hypoglycemia between Visit 1 and Visit 2. Unexplained refers to episodes of severe hypoglycemia that are not related to a dosing error, lack of or a change in meal size, or related to additional/unanticipated exercise
  • Any hospitalization or emergency room visit due to poor diabetic control within 6 months of Screening, or hospitalization or emergency room visit due to poor diabetic control between Visit 1 and Visit 2
  • Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the study, or a history of hypersensitivity to TI Inhalation Powder or to drugs with a similar chemical structure
  • History of recent blood transfusions (within previous 3 months), hemoglobinopathies, or any other conditions that affect HbA1c measurements.
  • History of COPD, asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis), or use of any medications for these conditions
  • Any clinically significant radiological findings on screening chest x-ray
  • Active respiratory infection within 30 days before Screening (subject may return after 30 days from resolution for rescreening)
  • Major organ system diseases, including: ? Seizure disorder; systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine; cancer (other than excised cutaneous basal cell carcinoma) or any history of lung neoplasms
  • Current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity; use of medications for weight loss (eg, sibutramine, orlistat) within 12 weeks of Screening; treatment with amiodarone within 12 weeks of Screening
  • Clinically significant abnormalities on screening laboratory evaluation or chest x-ray
  • Severe complications of diabetes, in the opinion of the PI, including symptomatic autonomic neuropathy; disabling peripheral neuropathy; active proliferative retinopathy; nephropathy with renal failure, renal transplant, or dialysis; nontraumatic amputations due to gangrene; or vascular claudication
  • Women who are pregnant, lactating, or planning to become pregnant during the clinical study period; women of childbearing potential (defined as premenopausal and not surgically sterilized or postmenopausal for fewer than 2 years) not practicing adequate birth control. Adequate birth control is defined as using oral, percutaneous, or transdermal contraceptives; condoms and diaphragms (double barrier) with a spermicide; or intrauterine devices. Postmenopausal for this study includes amenorrhea f
  • Current drug or alcohol abuse or a history of drug or alcohol abuse that, in the opinion of the PI, would make the subject an unsuitable candidate for participation in the study
  • Exposure to any investigational medications or devices within the previous 30 days before study entry
  • Unable to read or write, or unlikely to comprehend and follow the study protocol procedures; lack of compliance with medication or procedures that, in the PI's opinion, may affect the study data or subject safety and that precludes the subject from participation in the study; or any other concurrent medical or major psychiatric condition that, in the opinion of the PI, makes the subject unsuitable for the clinical study or could limit the validity of the informed consent or impair the subject'
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01445951

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Sponsors and Collaborators
Mannkind Corporation
  More Information

No publications provided

Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT01445951     History of Changes
Other Study ID Numbers: MKC-TI-171
Study First Received: September 30, 2011
Results First Received: July 22, 2014
Last Updated: October 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Insulin
Insulin Aspart
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 30, 2014