One Year, Open-Label Outpatient, Parallel Group Trial Assessing the Impact of the Availability of Inhaled Insulin (Exubera®) on Glycemic Control in Patients with Type 2 Diabetes Mellitus Who Are Poorly Controlled on a Minimum of Two Oral Anti Diabetic Agents. - N/A

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2004-001258-94-DE
• Date of registration: 19/10/2004
• Prospective Registration: Yes
• Primary sponsor: Pfizer Pharma GmbH
• Public title: One Year, Open-Label Outpatient, Parallel Group Trial Assessing the Impact of the Availability of Inhaled Insulin (Exubera®) on Glycemic Control in Patients with Type 2 Diabetes Mellitus Who Are Poorly Controlled on a Minimum of Two Oral Anti Diabetic Agents. - N/A
• Scientific title: One Year, Open-Label Outpatient, Parallel Group Trial Assessing the Impact of the Availability of Inhaled Insulin (Exubera®) on Glycemic Control in Patients with Type 2 Diabetes Mellitus Who Are Poorly Controlled on a Minimum of Two Oral Anti Diabetic Agents. - N/A
• Date of first enrolment: 23/12/2005
• Target sample size: 648
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001258-94
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Male and female patients meeting all criteria listed below will be included in the study:

1. Age = 35 years and = 80 years with a diagnosis of type 2 diabetes made = 6 months prior to study entry, as defined by the American Diabetes Association (Diabetes Care 25:S5-S20, 2002).

2. HbA1c = 8.0% at screening.

3. Body Mass Index (BMI) =23 kg/m2 and = 40 kg/m2 (See BMI Table Appendix E).

4. Patients must have documentation of a fully dilated ophthalmologic exam
performed within 1 year of screening in accordance with local guidelines. The documentation must be obtained prior to randomization. This information is of importance e.g., in case proliferative retinopathy is diagnosed while aggressive glucose lowering is considered in the study.

5. Currently treated and on a stable dose of at least two oral hypoglycemic agents for at least 3 months prior study entry with at least half maximum dose per country guidelines or half maximum tolerable dose.

6. Written informed consent obtained PRIOR to performing screening evaluations.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Type 1 diabetes

2. Known allergy to insulin

3. Smoking: current or any in the past 6 months; smoking is not permitted at any time during the study

4. Current treatment with insulin or discontinued from insulin within the past three months

5. “Brittle” diabetes or a predisposition to severe hypoglycemia. Severe hypoglycemia is defined in Section 10.11.2. of the protocol.

6. Metabolic Conditions:
a) Significant hypoglycemia risk
b) Current chronic inhaled or systemic corticosteroid treatment likely to be of metabolic effect

7. Active Liver disease

8. Pulmonary Conditions:
a) Frankly abnormal PFTs at Week –1, defined as DLco >120% or <70%; TLC >130% or <70%; or FVC or FEV1 <70% of predicted.
b) Clinically significant abnormalities on screening chest X-ray (or chest MRI). Subjects with radiographically stable and clinically insignificant abnormalities need not be excluded. Documentation of stability requires comparison with previous radiographs obtained at least 6 months earlier.
c) Significant pulmonary diseases

9. Cardiovascular conditions:
a) Significant cardiovascular dysfunction and/or history including hospitalization within the preceding six months.
b) Poorly-controlled hypertension (systolic blood pressure > 180 mmHg, diastolic blood pressure > 110 mmHg) on two readings (sitting).
c) Abnormal screening ECG:
i) predominant rhythm other than normal sinus
ii) A-V block greater than first degree
iii) resting heart rate > 100 or < 50 bpm
The principal investigator, or other designated physician at each site, will be responsible for deciding the clinical significance of any abnormal ECG findings.

10. Kidney disease:
a) History of renal transplantation or current renal dialysis
b) Clinical nephrotic syndrome, or significant renal dysfunction or disease based on estimated creatinine clearance < 65 mL/min (25), and/or a serum creatinine greater or equal to 1.5 mg/dl (133 µmol/L) in males and greater or equal to 1.4 mg/dl (124 µmol/L) in females and /or BUN >50 mg/dl, whichever is worse.

11. Psychological
a) History of substance abuse or alcoholism within the past 5 years
b) Psychiatric disorders that would interfere with the patient’s ability to complete the study

12. Neurological
a) Seizure disorder
b) Significant gastroparesis or orthostatic hypotension (autonomic neuropathy)

13. Any current malignancy except:
a) those = 5 years ago without recurrence
b) excised basalioma or squamous cell cancer

14. Clinically significant abnormalities on screening laboratory evaluation

15. Clinically significant major organ system disease

16. Patients with circumstances or abnormalities (e.g., blindness or a history of non-compliance) that would interfere with the interpretation of safety or efficacy data or the completion of the study

17. Unable and/or unlikely to comprehend and/or follow the study protocol (including blood glucose monitoring) and complete Patient Reported Outcomes questionnaire. Unable and/or unlikely to comprehend how to use the inhaler device or inability to use the inhaler device

18. Failure to adhere to protocol requirements during the run-in period

19. Pregnant or intent to become pregnant OR BREASTFEEDING during study or absence of adequate birth control measures

20. Inpatient surgery anticipated during the study period

21. Known interference with HbA1c determination: hemoglobinopathy or chronic anemia

22. Investigator or immediate family

23. Donation of blood or blood

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 diabetes mellitus
MedDRA version: 7 Level: LLT Classification code 10012601

Intervention(s)

Trade Name: Exubera 1 mg
Product Name: Exubera (inhaled insulin)
Product Code: CP-464005
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Insulin human
Current Sponsor code: CP-464005
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1 -

Trade Name: Exubera 3 mg
Product Name: Exubera (inhaled insulin)
Product Code: CP-464005
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Insulin human
Current Sponsor code: CP-464005
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Primary Outcome(s)

Primary end point(s): The primary objective of this study is to demonstrate that mean the reduction in HbA1c after 26 weeks (approx. 6 months) of treatment is greater in patients to whom inhaled insulin is made available compared to patients to whom it is not. Thus, the primary efficacy variable is the difference in HbA1c between baseline (Week -2) and the end of the treatment period at week 52, in the intention-to-treat (ITT) population

Main Objective: To demonstrate that mean reduction in HbA1c after 26 weeks (approx. 6 months) is greater in patients to whom inhaled insulin is made available compared to patients to whom it is not.

Secondary Objective: Secondary endpoints which will be assessed at endpoint (12 months) and at week 26 (approx. 6 months) as part of an interim analysis:
· HbA1c at week 52, ITT population
· Proportion of patients achieving glycemic control (HbA1c = 6.5%, = 7.0%)
· The time it takes to get to “be treated with” insulin (inhaled or SC)
· Change from baseline in fasting plasma glucose level
· Incidence and severity of hypoglycemia
· Change from baseline in body weight and body mass index
· Change from baseline in fasting lipid profile
· Treatment categories: Inhaled insulin, SC insulin, changed oral agents, no change in treatment choice.
· Number of patients who discontinue due to insufficient clinical response
· Pulmonary function
· Insulin antibody titers
· Incidence of clinical adverse events
· Pharmaco-economic impact

Secondary ID(s)

N/A

A2171018