Comparison of Technosphere® Insulin Versus Technosphere Powder (Placebo) in Insulin-Naive Subjects With Type 2 Diabetes Mellitus

Type 2 Diabetes Clinical Trial

Official title:

A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized, Clinical Trial Evaluating the Efficacy and Safety of Prandial Technosphere® Insulin Inhalation Powder Versus Technosphere Inhalation Powder in Insulin Naïve Subjects With Type 2 Diabetes Mellitus Poorly Controlled With Oral Antidiabetic Agents Over a 24 Week Treatment Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01451398
• Other study ID #: MKC-TI-175
• Secondary ID: Affinity2
• Status: Completed
• Phase: Phase 3
• First received: October 7, 2011
• Last updated: October 9, 2014
• Start date: November 2011
• Est. completion date: July 2013

Study information

• Verified date: October 2014
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Insulin-naive subjects with Type 2 Diabetes Mellitus who are sub-optimally controlled on either maximum tolerated dose of metformin or maximum tolerated dose of metformin plus one or two other oral anti-diabetic medications will have either Prandial Technosphere® Insulin or Technosphere Powder (placebo) added to their oral antidiabetic drugs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: July 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HbA1c > or = to 7.5% and < or = to 10.0%

• Body mass index (BMI) < or = to 45 kg/m2

• Non smoker for at least 6 months before Screening

• Clinical diagnosis of type 2 diabetes mellitus for more than 12 months

• Currently receiving as diabetes treatment only metformin or 2 or more OADs and on stable doses for at least 3 months before enrollment

• Subjects receiving metformin must be on at least 1.5gm daily, or up to the maximum tolerated dose

• Subjects treated with a sulfonylurea must be on at least 50% of the total maximum approved dose for a given agent

• Subjects receiving a DPP-4 inhibitor must receive the maximum approved dose specific for that agent

• Metiglinide and alpha-glucoside inhibitors must be taken at the highest tolerated dose within the approved dose range

• No previous or current treatment with insulin, except during an acute illness, gestational diabetes, or at time of initial diagnosis of diabetes

• Forced expiratory volume in one second (FEV1) > or = to 70% Third National Health and Nutrition Examination Survey (NHANES III) predicted

• Forced vital capacity (FVC) > or = to 70% NHANES III predicted

• Forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC) > or = to NHANES III lower limit of normal (LLN)

Exclusion Criteria:

• History of chronic obstructive pulmonary disease (COPD), clinically proven 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 (proliferative retinopathy, autonomic neuropathy with symptoms of gastroparesis or cardiac arrhythmia; sensory neuropathy that makes manipulation of the Gen2C inhaler difficult)

• Renal disease or renal dysfunction

• Significant cardiovascular dysfunction or history thereof within 12 months of screening; serious arrhythmia, treatment with medications to control/treat arrhythmias; myocardial infarction; cardiac surgery; history of valvular heart disease

• Previous or current use of amiodarone

• Treatment with glucagon-like peptide-1 (GLP-1) analogs, thiazolidinediones (TZD), or weight loss drugs (eg, sibutramine, orlistat) within 3 months of screening

• History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening

• History of recent blood transfusion (within previous 3 months) or diagnosis of hemoglobinopathies that may affect HbA1c measurements

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Technosphere® Insulin
Technosphere® Insulin Inhalation Powder
• Technosphere Powder
Placebo Comparator

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Countries where clinical trial is conducted

United States,  Brazil,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 24 in HbA1c	Efficacy as measured by change in glycated hemoglobin (HbA1c) at Week 24	Baseline to Week 24	No
Secondary	Proportion of Responders Achieving HbA1c <= 7.0%	Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%	Week 24	No
Secondary	Proportion of Responders Achieving HbA1c <= 6.5%	Efficacy as measured in proportion of subjects achieving HbA1c < or = to 6.5% at Week 24	Week 24	No
Secondary	FPG Change From Baseline to Week 24	Efficacy as measured by mean change in fasting plasma glucose (FPG)	Baseline to Week 24	No
Secondary	Proportion of Subjects Requiring Rescue Therapy		Baseline to Week 24	No
Secondary	Time to Rescue	Time from Week 0 (baseline) to initiation of rescue therapy (up to a maximum of 24 weeks/end of treatment) for subjects not responding to treatment	Baseline to Week 24	No
Secondary	FEV1 Change From Baseline to Week 24	Forced Expiratory Volume in 1 second - change from baseline to week 24	Baseline to Week 24	Yes
Secondary	Incidence of Total Hypoglycemia	Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.	Baseline to Week 24	Yes
Secondary	Incidence of Severe Hypoglycemia	Severe Hypoglycemia defined as: Requiring 3rd party assistance.	Baseline to Week 24	Yes
Secondary	Total Hypoglycemia Event Rate	Number of Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24	Yes
Secondary	Severe Hypoglycemia Event Rate	Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)	Baseline to Week 24	Yes
Secondary	Mean 7-point Glucose Baseline Values	Mean 7-point self-monitored glucose at baseline	Baseline	No
Secondary	Mean 7-point Glucose Week 24 Values	Mean 7-point self-monitored blood glucose at Week 24	Week 24	No
Secondary	Change in Body Weight From Baseline to Week 24	Change in body weight from Baseline to Week 24	Baseline to Week 24	No