A SIX MONTH, OPEN-LABEL OUTPATIENT, RANDOMIZED PARALLEL GROUP TRIAL ASSESSING THE IMPACT OF DRY POWDER INHALED INSULIN (EXUBERA®) ON GLYCEMIC CONTROL COMPARED TO INSULIN GLARGINE (LANTUS®) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS WHO ARE POORLY CONTROLLED ON A COMBINATION OF TWO OR MORE ORAL AGENTS - N/A

• Register: EUCTR
• Last refreshed on: 11 November 2013
• Main ID: EUCTR2006-004421-28-BE
• Date of registration: 14/11/2006
• Prospective Registration: Yes
• Primary sponsor: Pfizer N.V./S.A.
• Public title: A SIX MONTH, OPEN-LABEL OUTPATIENT, RANDOMIZED PARALLEL GROUP TRIAL ASSESSING THE IMPACT OF DRY POWDER INHALED INSULIN (EXUBERA®) ON GLYCEMIC CONTROL COMPARED TO INSULIN GLARGINE (LANTUS®) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS WHO ARE POORLY CONTROLLED ON A COMBINATION OF TWO OR MORE ORAL AGENTS - N/A
• Scientific title: A SIX MONTH, OPEN-LABEL OUTPATIENT, RANDOMIZED PARALLEL GROUP TRIAL ASSESSING THE IMPACT OF DRY POWDER INHALED INSULIN (EXUBERA®) ON GLYCEMIC CONTROL COMPARED TO INSULIN GLARGINE (LANTUS®) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS WHO ARE POORLY CONTROLLED ON A COMBINATION OF TWO OR MORE ORAL AGENTS - N/A
• Date of first enrolment: 01/03/2007
• Target sample size: 478
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004421-28
• 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: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Finland, France, Germany, Netherlands, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Male and female subjects meeting all of the following criteria will be considered for enrollment into the study.
1. Age = 30 years with a diagnosis of type 2 diabetes mellitus made = 6 months prior to study entry, as defined by the American Diabetes Association (Diabetes Care 25: S5-S20, 2002).
2. Screening HbA1c = 7.0%
3. Currently treated on a stable dose of at least 2 oral hypoglycemic agents which must include combinations of sulfonylureas and metformin for at least 3 months prior to study entry. If a subject on a non-sulfonylurea secretagogue can be switched to glimepiride 2 mg at visit 2, they may be screened. Treatment with thiazolidinediones is permitted in addition to the sulfonylurea and metformin where concurrent treatment with insulin is permitted.
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:
Subjects presenting with any of the following will not be included in the trial:
1. Patients with Type 1 diabetes mellitus as defined by ADA.
2. Patients with type 2 diabetes mellitus currently (last three months) treated with an insulin regimen (only or associated to oral hypoglycemic agents (OHAs).
3. Patients with type 2 diabetes mellitus who are treated with thiazolidinediones where per local regulation concurrent use of insulin with thiazolidinediones is prohibited.
4. Patients taking any of the following hypoglycemic agents or agents within the following classes of drugs: repaglinide, nateglinide, exenatide, and dipeptidyl peptidase-4 inhibitors such as vildagliptin; rosiglitazone and pioglitazone where concurrent use of these agents with insulin is not permitted.
5. Active liver disease; significantly-impaired hepatic function, as shown by, but not limited to, ALAT (SGPT) or ASAT (SGOT) above 2x the upper limit of normal as measured at visit 1.
However, patients with elevated ALT >1.5 UNL as a result of hepatic steatosis are permitted to enter the study.
6. Significant kidney disease:
a. History of renal transplantation or current renal dialysis or
b. Serum creatinine > 1.5 mg/dl (= 133 µmol/L) in males and > 1.4 mg/dl (= 124 µmol/L) in females and/or BUN > 50 mg/dl or
c. Urinary albumin/creatinine ratio >2.5 mg/mmol in men and >3.5 mg/mmol in women or
d. Clinical nephrotic syndrome
7. Any other clinically significant abnormalities on screening laboratory evaluation (unless discussed with the monitor and approved by the study management).
8. Patients who do not have documentation of an ophthalmologic exam performed in the 12 months prior to visit 1 in accordance with local guidelines.
9. Active proliferative diabetic retinopathy, as defined by the application of focal or pan retinal photocoagulation or vitrectomy, in the 12 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require surgical treatment (including laser photocoagulation) during the study.
10. Donation of blood or transfusion during the 2 months prior to visit 1.
11. Pregnant or lactating women, or females of child-potential who are unwilling or unable to use adequate contraception to prevent pregnancy during the study.
12. Treatment with any investigational drug including inhaled insulin in the 3 months prior to visit 1 (screening).
13. Significant pulmonary diseases including:
o FEV1 <70% of predicted.
o History of moderate or severe asthma including those with daily symptoms and/or
require daily use of inhaled short acting beta2-agonist.
o History of moderate or severe COPD including those requiring regular use of one
or more bronchodilators (beta2-agonists, anticholinergics, methylxanthines).
However, short acting bronchodilators used as needed are allowed.Poorly controlled asthma, clinically significant obstructive pulmonary disease or other significant respiratory disease.
14. Smoking within the last 6 months prior to the study. Smoking is not permitted at any time during this study.
15. Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.
16. Any clinically significant major organ system disease such as relevant cardiovascular, gastrointestinal, hepatic, neurological, endocrine, haematological or other major systemic diseases making implementation of the protocol or interpretation of the study results difficult. However, wellcontrolled, stable disorders a

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

Health Condition(s) or Problem(s) studied

Diabetes Mellitus type II (not insulin independent)
MedDRA version: 8.1 Level: LLT Classification code 10012601 Term: Diabetes mellitus

Intervention(s)

Trade Name: Exubera®
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Insulin Human
CAS Number: 11061-68-0
Other descriptive name: CP 464005
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Exubera®
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Insulin Human
CAS Number: 11061-68-0
Other descriptive name: CP 464005
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Trade Name: Lantus®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Insulin glargine
CAS Number: 160337-95-1
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: The primary objective of the study is to demonstrate non-inferiority of dry powder inhaled insulin (Exubera®) compared to insulin Glargine (Lantus®) in terms of glycemic control (HbA1c) after 26 weeks of treatment.

Secondary Objective: Secondary objectives of the study are to demonstrate superiority of inhaled insulin over insulin Glargine on the following endpoints: change of fasting glucose and postprandial glucose excursions from baseline to end of the treatment period, the percentage of subjects who have an HbA1c of less than 6.5%, 7.0%, or 8.0% at
the end of the treatment period, rates of overall and nocturnal hypoglycemia, changes in body weight and BMI, glucose excursions over 24 hours in a subset of subjects, and patient reported outcomes at week 26 compared to baseline. Additional secondary objectives are changes in urinary free 8 iso-prostaglandin F2a in a subset of patients, high sensitive C-reactive protein, interleukin 6 (IL-6), thrombin-antithrombin complexes (tat-complexes), and soluble tissue factor from baseline to end of the treatment period.

Primary end point(s): The primary endpoint is the change from baseline to HbA1c measured at week 26 (approx. 6 months) after treatment.

Secondary ID(s)

A2171084

2006-004421-28-NL

N/A