Diabetes Mellitus, Type 2
Conditions
Brief summary
The primary objective of this study is to assess whether a simple initial dose prescription of inhaled insulin (Exubera) achieves glycemic control (HbA1c) after 16 weeks that is non-inferior compared to the standard weight-based formula.
Interventions
Initial dose (mg) as per weight based formula = 0.05 x body weight (kg) TID
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diabetes mellitus Type 2 * Currently treated with at least 2 oral anti-diabetic agents
Exclusion criteria
* Severe Asthma, severe COPD * Smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline | From baseline to week 16 | Mean change of hemoglobin A1c (HbA1c %) from baseline to week 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | From baseline to week 16 | Mean change of fasting plasma glucose, and overall absolute (based on the mean of 7-point home blood glucose monitoring (HGM) values), pre- and post-meal blood glucose (based on the mean of pre- or post-meal HGM values). Change from pre- to post-meal blood glucose based on the mean of difference of pre-meal HGM values from post-meal HGM values. |
| Number of Subjects Who Experienced Hypoglycemia and Nocturnal Hypoglycemia | week 16 | Cumulative Number Subjects Who Experienced Hypoglycemia & Nocturnal Hypoglycemia. Hypoglycemia:1)Clinical picture includes prompt resolution with food intake, subcutaneous glucagon, or intravenous glucose, 2)blood glucose check showing glucose \<3.27 mmol/L (59 mg/dl), 3)glucose measurement of 2.7 mmol/L (49 mg/dl) or less, with or without symptoms. |
| Hypoglycemia Event Rate Per Month | up to week 4 or 16 | Monthly event rate was calculated as the daily event rate multiplied by 30, and the daily event rate was calculated as the total number of events divided by the days in study up to the specified timepoint (ie, Week 4 or Week 16). |
Countries
Hong Kong, Pakistan, Philippines, Singapore
Participant flow
Recruitment details
Five centers in the Philippines, 2 centers in Singapore, 1 center in Hong Kong, and 1 center in Pakistan enrolled subjects.
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 before it had recruited targeted number of subjects and followed them for the per protocol specified period.
Participants by arm
| Arm | Count |
|---|---|
| Exubera Dose of 1mg Three Times Daily (TID) Subjects in Group A self-administered 1 mg Exubera TID before each meal (breakfast, lunch, and dinner) | 25 |
| Exubera Dose (mg) as Per Weight Based Formula TID Group B self-administered a dose of Exubera that was determined by the body weight-based formula = 0.05 x body weight (kg) TID. | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study terminated by sponsor | 23 | 21 |
Baseline characteristics
| Characteristic | Exubera Dose of 1mg Three Times Daily (TID) | Exubera Dose (mg) as Per Weight Based Formula TID | Total |
|---|---|---|---|
| Age, Customized 18 - 44 years | 3 participants | 5 participants | 8 participants |
| Age, Customized <18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized 45 - 64 years | 20 participants | 17 participants | 37 participants |
| Age, Customized >= 65 years | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / — | 15 / — |
| serious Total, serious adverse events | 2 / — | 0 / — |
Outcome results
Primary
Change in HbA1c From Baseline
Mean change of hemoglobin A1c (HbA1c %) from baseline to week 16
Time frame: From baseline to week 16
Population: Full analysis set (FAS) population - descriptive statistics were produced using last observation carried forward (LOCF) for Week 16, therefore all subjects are included in the Week 16 data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exubera Dose of 1mg Three Times Daily (TID) | Change in HbA1c From Baseline | -1.9 Percent | Standard Deviation 1.56 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Change in HbA1c From Baseline | -2.0 Percent | Standard Deviation 1.17 |
Secondary
Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF)
Mean change of fasting plasma glucose, and overall absolute (based on the mean of 7-point home blood glucose monitoring (HGM) values), pre- and post-meal blood glucose (based on the mean of pre- or post-meal HGM values). Change from pre- to post-meal blood glucose based on the mean of difference of pre-meal HGM values from post-meal HGM values.
Time frame: From baseline to week 16
Population: FAS - descriptive statistics were produced using LOCF for Week 16, therefore all subjects are included in the Week 16 data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exubera Dose of 1mg Three Times Daily (TID) | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Overall absolute blood glucose | -2.5 mmol/l | Standard Deviation 3.62 |
| Exubera Dose of 1mg Three Times Daily (TID) | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Post-meal blood glucose | -4.1 mmol/l | Standard Deviation 3.78 |
| Exubera Dose of 1mg Three Times Daily (TID) | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Pre-meal blood glucose | -1.7 mmol/l | Standard Deviation 3.58 |
| Exubera Dose of 1mg Three Times Daily (TID) | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Change from pre-meal to post-meal blood glucose | -2.5 mmol/l | Standard Deviation 2.14 |
| Exubera Dose of 1mg Three Times Daily (TID) | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Fasting plasma glucose | -1.8 mmol/l | Standard Deviation 2.36 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Change from pre-meal to post-meal blood glucose | -2.1 mmol/l | Standard Deviation 2.96 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Fasting plasma glucose | -2.9 mmol/l | Standard Deviation 5.62 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Overall absolute blood glucose | -4.3 mmol/l | Standard Deviation 4.2 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Pre-meal blood glucose | -3.3 mmol/l | Standard Deviation 4.05 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Fasting Plasma Glucose, and Overall Absolute, Pre-meal, and Post-meal Blood Glucose Change From Baseline to Week 16 (LOCF) | Post-meal blood glucose | -5.5 mmol/l | Standard Deviation 4.28 |
Secondary
Hypoglycemia Event Rate Per Month
Monthly event rate was calculated as the daily event rate multiplied by 30, and the daily event rate was calculated as the total number of events divided by the days in study up to the specified timepoint (ie, Week 4 or Week 16).
Time frame: up to week 4 or 16
Population: FAS Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exubera Dose of 1mg Three Times Daily (TID) | Hypoglycemia Event Rate Per Month | up to week 4 (GrpA:n=8, GrpB:n=4) | 3.3 event rate per month | Standard Deviation 3.3 |
| Exubera Dose of 1mg Three Times Daily (TID) | Hypoglycemia Event Rate Per Month | up to week 16 (GrpA:n=12, GrpB:n=5) | 2.4 event rate per month | Standard Deviation 2.4 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Hypoglycemia Event Rate Per Month | up to week 4 (GrpA:n=8, GrpB:n=4) | 8.3 event rate per month | Standard Deviation 9.1 |
| Exubera Dose (mg) as Per Weight Based Formula TID | Hypoglycemia Event Rate Per Month | up to week 16 (GrpA:n=12, GrpB:n=5) | 2.5 event rate per month | Standard Deviation 1.3 |
Secondary
Number of Subjects Who Experienced Hypoglycemia and Nocturnal Hypoglycemia
Cumulative Number Subjects Who Experienced Hypoglycemia & Nocturnal Hypoglycemia. Hypoglycemia:1)Clinical picture includes prompt resolution with food intake, subcutaneous glucagon, or intravenous glucose, 2)blood glucose check showing glucose \<3.27 mmol/L (59 mg/dl), 3)glucose measurement of 2.7 mmol/L (49 mg/dl) or less, with or without symptoms.
Time frame: week 16
Population: FAS Population - Descriptive statistics were produced using LOCF for Week 16, therefore all subjects are included in the Week 16 data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exubera Dose of 1mg Three Times Daily (TID) | Number of Subjects Who Experienced Hypoglycemia and Nocturnal Hypoglycemia | Hypoglycemia | 12 participants |
| Exubera Dose of 1mg Three Times Daily (TID) | Number of Subjects Who Experienced Hypoglycemia and Nocturnal Hypoglycemia | Nocturnal hypoglycemia | 2 participants |
| Exubera Dose (mg) as Per Weight Based Formula TID | Number of Subjects Who Experienced Hypoglycemia and Nocturnal Hypoglycemia | Nocturnal hypoglycemia | 2 participants |
| Exubera Dose (mg) as Per Weight Based Formula TID | Number of Subjects Who Experienced Hypoglycemia and Nocturnal Hypoglycemia | Hypoglycemia | 5 participants |