A Clinical Trial Comparing Efficacy and Safety of Exubera® and Humalog®

A 52-Week Multicenter, Open-Label, Randomized, Parallel, Two - Arm Study Comparing Exubera® (Inhaled Human Insulin) Vs. Humalog® (Insulin Lispro), Both In Combination With Insulin Glargine In Subjects With Type 1 Diabetes Mellitus

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00356421

Enrollment

Registered

2006-07-26

Start date

2006-11-30

Completion date

2008-06-30

Last updated

2009-09-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 1

Brief summary

To compare efficacy and safety of Exubera® vs Humalog in patients with type 1 diabetes mellitus

Detailed description

Pfizer announced in October 2007 that it would stop marketing Exubera®. At that time recruitment for study, A2171035 was placed on hold. Nektar, the company from which Pfizer licensed Exubera®, announced on April 9, 2008 that it had stopped its search for a new marketing partner. Accordingly, there will be no commercial availability of Exubera®. As a result, study A2171035 was terminated on May 12, 2008. Neither safety nor efficacy reasons were the cause of the study termination.

Interventions

DRUGInhaled Human Insulin (Exubera®)

Preprandial inhaled insulin regimen and administration of insulin glargine QD

DRUGInsulin lispro (Humalog)

Subcutaneous insulin regimen of pre-prandial insulin lispro and administration of insulin glargine QD.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diabetes mellitus Type 1

Exclusion criteria

* Severe Asthma, severe Chronic Obstructive Pulmonary Disease (COPD) * Smoking

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Glycosylated Hemoglobin (HbA1c) Percent (%)	At 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.

Secondary

Measure	Time frame	Description
Percentage of Subjects Who Attained HbA1c Levels of <8%, <7%, <6.5%, and >=8%	At 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Percentage of Subjects With Absolute Reduction in HbA1c Levels From Baseline of >0.5%, >0.7% and >1.0%	At 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Percentage of Subjects Who Attained Target Fasting Plasma Glucose (FPG) Values (4.0 to 6.5 mmol/l; 72 to 117 mg/dl) From Baseline	At weeks 2, 4, 6, 12, 24, 36, and 52 or last observation.	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in FPG	At 52 weeks or last observation	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Fasting Blood Glucose Based on Glucometer Data and In-hospital Assessments	To 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Post-prandial Blood Glucose Based on Glucometer Data and In-hospital Assessments	To 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Insulin Antibody Levels	At weeks 24 and 52 or last observation.	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Blood Glucose Values From Baseline Determined by Home-monitored Blood Glucose (Subject Recorded Worksheet Values)	To 52 weeks.	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change in Fasting Lipids From Baseline	At weeks 24 and 52 or last observation	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Body Weight	At weeks 12, 24, 36, and 52 or last observation.	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Body Mass Index	At weeks 12, 24, 36, and 52 or last observation.	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Basal Insulin Doses	To 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Change From Baseline in Prandial Insulin Doses	To 52 weeks	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.

Other

Measure	Time frame	Description
Subject Reported Health State From Baseline as Measured in the EuroQol-5 Dimensions (EQ-5D) Questionnaire	At weeks 6, 24, and 52 or last observation	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.
Subject Reported Quality of Life From Baseline as Determined From Phase V System Measurement	At weeks 6, 24, and 52 or last observation	As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study. No efficacy data were summarized due to limited enrollment/early termination.

Countries

Austria, Belgium, Denmark, Finland, France, Ireland, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom, United States

Participant flow

Recruitment details

A total of 340 subjects were planned to be randomized; 87 were screened and 58 were randomized to study treatment prior to study termination.

Pre-assignment details

As a result of Pfizer's decision (18Oct2007) to return the worldwide rights for Exubera ® (insulin human \[rDNA origin\]) Inhalation Powder) to Nektar, from which Pfizer licensed inhaled insulin technology, it was decided to terminate this study.

Participants by arm

Arm	Count
Exubera ® Preprandial inhaled insulin regimen plus once daily (QD) administration of insulin glargine.	38
Insulin Lispro Subcutaneous (SC) insulin regimen of pre-prandial insulin lispro and QD administration of insulin glargine.	20
Total	58

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lack of Efficacy	3	0
Overall Study	Not related to study drug	5	3
Overall Study	Related to study drug	15	12
Overall Study	Withdrawal by Subject	9	2

Baseline characteristics

Characteristic	Exubera ®	Insulin Lispro	Total
Age, Customized 18 - 44 years	22 participants	13 participants	35 participants
Age, Customized 45 - 64 years	14 participants	6 participants	20 participants
Age, Customized >=65 years	2 participants	1 participants	3 participants
Sex: Female, Male Female	17 Participants	6 Participants	23 Participants
Sex: Female, Male Male	21 Participants	14 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	35 / —	20 / —
serious Total, serious adverse events	2 / —	1 / —

Outcome results

Primary

Change From Baseline in Glycosylated Hemoglobin (HbA1c) Percent (%)

Time frame: At 52 weeks

Population: Intent to Treat (ITT) population. Due to low number of subjects that completed, no descriptive statistics for the efficacy endpoints are provided.

Secondary