A Phase 3, Open-Label, Three-Group Parallel Study to Evaluate the Efficacy and Safety of Human Insulin Inhalation Powder (HIIP) in Patients with Type 2 Diabetes Treated with Once-Daily Insulin Glargine - IDBA

• Conditions: Male or female nonsmoking patients 18 years of age or older; have had type 2 diabetes mellitus for at least 6 months at study entry and have been treated with one or more oral antihyperglycemic medications on a stable dose for at least 6 weeks (3 months for thiazolidinediones [TZDs]) and once-daily insulin glargine for at least 4 months, have FEV1 and DLCO >70% predicted, and have an HbA1c between 7.5% and 9.5% at screening.

• Registration Number: EUCTR2006-000247-26-GB
• Lead Sponsor: Eli Lilly and Company Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-10
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

Patients are eligible to be included in the study only if they meet all of the following
criteria at screening or otherwise as described below:
[1] Are male or female who are 18 years of age or older,
[2] Have had type 2 diabetes mellitus, based on the disease diagnosis
criteria (Section 4.1.1), for at least 6 months’ duration at study entry,
[3] Have been treated with the following regimen:
• one or more oral antihyperglycemic medications on a stable dose
for at least 6 weeks (3 months for thiazolidinediones [TZDs])
AND
• once-daily insulin glargine for at least 4 months
[4] Have HbA1c =7.5 and =10.5% at screening
• If the HbA1c criterion is not met at the first screening visit, the
patient may undergo retest of HbA1c once within a 3-month
period. If less than 1 month has passed since the initial screening,
only the HbA1c test will be repeated. If more than 1 month, but
less than 3 months have passed, the entire screening panel except
cotinine will be repeated.
• Retesting may occur as long as the screening period for the study is
still ongoing at the time of the retest.
•Patients who were screened for this study prior to the approval of protocol amendment b and who failed to meet this inclusion criterion due to an HbA1c of > 9.5% may be rescreened if the screening HbA1c was also = 10.5%.
[5] If female, are not breastfeeding
AND
If female and of childbearing potential (not surgically sterilized and
between menarche and 1 year postmenopause), must
• test negative for pregnancy at the time of screening based on a
urine or serum test,
• intend not to become pregnant during the study,
• agree to use a reliable method of birth control (for example, use of
oral contraceptives or Norplant®; a reliable barrier method of birth
control [diaphragms with contraceptive jelly; cervical caps with
contraceptive jelly; condoms with contraceptive foam; intrauterine
devices]; partner with vasectomy) during the study.

[6] Are nonsmokers, have not smoked for at least 6 months prior to
entering the study, and agree not to smoke (cigars, cigarettes, or pipes)
or use smokeless tobacco for the duration of the study. Serum cotinine
level must be <20 ng/mL at screening.
• If the patient is a nonsmoker for a period of =6 months, and the
serum cotinine level is =20 and =100 ng/mL, the patient may
undergo retesting of serum cotinine once within 4 weeks.
• Retesting may occur as long as the screening period for the study is
still ongoing at the time of the retest.
[7] Are able to perform pulmonary function testing, according to
guidelines from the American Thoracic Society (ATS) (1995),
[8] Have PFTs graded as A,” B,” or C” in quality (see Section 6.3.3.1)
and satisfy all of the following criteria for PFTs:
• DLCO >70% of predicted,
• FEV1/FVC > lower limit of normal and FEV1 >70% predicted,
• Patients should be able to perform at least three acceptable FEV1,
FVC, and two acceptable DLCO maneuvers, two of which are
reproducible (within 0.20 L for FEV1 and FVC; and within
2.5 standard DLCO units for DLCO).
o If the patients are not able to meet the reproducibility criteria
for FEV1, FVC, or DLCO maneuvers, they may return for retest
within a 4-week period as described in Section 6.3.3.1.
o If the grade for FEV1, FVC, or DLCO is D” or F,” then the
patients may return for retest as described in Section 6.3.3.1.
o Retesting may occur as long as the screening period for the
study is still ongoing at the time of the retest.
[9] Have a chest x-ray without evidence o

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:
[11] Are investigative site personnel directly affiliated with the study,
and/or their immediate families. Immediate family is defined as a
spouse, parent, child, or sibling, whether biological or legally adopted.
[12] Are Lilly or Alkermes employees,
[13] Have received treatment within the last 30 days with a drug that has
not received regulatory approval for any indication at the time of study
entry,
[14] Patients who have previously completed or withdrawn from this study
or any study investigating any form of inhaled insulin and took one or
more doses of inhaled insulin, or have previously taken any form of
inhaled insulin,
[15] Are taking a TZD dose greater than what is indicated in combination
with insulin according to the TZD label in the respective country (for
example, in the United States, rosiglitazone greater than 4 mg daily or
pioglitazone greater than 45 mg daily is not currently indicated). In the UK, patients who are on a TZD and glargine at study entry may be enrolled, if the patient is classified as NYHA I, and has been stable (from a cardiovascular perspective) while on this medication combination. In other
countries where the combination of the TZD and insulin is not
approved, patients taking any TZD at study entry will be excluded.
[16] Have had more than two episodes of severe hypoglycemia during the
6 months prior to study entry (see Section 5.9 for information about
severe hypoglycemia),
[17] Have had more than one hospitalization or emergency room visit due
to poor diabetic control during the 6 months prior to study entry,
[18] Have had a lower respiratory infection in the 3 months prior to
screening, evidenced by diagnosed pneumonia (on clinical or
radiologic grounds),
[19] Have received systemic glucocorticoid therapy within the 3 months
prior to study entry (topical preparations, nasal preparations,
intra-articular administration, as well as physiologic replacement for
Addison’s Disease and hypopituitarism are permitted),

[20] Have obvious clinical signs or symptoms of liver disease, acute or
chronic active hepatitis, or alanine aminotransaminase/serum glutamic
pyruvic transaminase (ALT/SGPT) greater than three times the upper
limit of the reference range,
[21] Have a history of renal transplantation, are currently receiving renal
dialysis, or have a serum creatinine >2.0 mg/dL (177 µmol/L) if not on
metformin; or if on metformin at study entry, have a serum creatinine
above what is contraindicated in the metformin label in the respective
country (for example, in the United States, =1.5 mg/dL [132 µmol/L]
for males or =1.4 mg/dL [123 µmol/L] for females),
[22] Have a history of angina, myocardial infarction, or Functional Capacity Class II,III/IV cardiac disease (patients taking a TZD), Functional
Capacity Class III/IV cardiac disease (patients not taking a TZD) (as defined by the New York
Heart Association [Attachment IDBA.5]) within the 6 months prior to
study entry.
[23] Have an active or untreated malignancy, or have been in remission
from a clinically significant malignancy (other than basal cell or
squamous cell skin cancer, in situ carcinoma of the cervix, or in situ
prostate cancer) for less than 5 years,
[24] Have a current or past history of lung cancer,
[25] Have a history of lung transplantation,
[26] Have a current diagnosis or past history of asthma, chronic obstructive
pulmonary disease (COPD), cystic fibro

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified