A Clinical Trial Comparing Efficacy and Safety of Exubera® and Humalog® - Study Results

Study Type:	Interventional
Study Design:	Randomized, Open Label, Parallel Assignment
Condition:	Diabetes Mellitus, Type 1
Interventions:	Drug: Inhaled Human Insulin (Exubera®) Drug: Insulin lispro (Humalog)

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 340 subjects were planned to be randomized; 87 were screened and 58 were randomized to study treatment prior to study termination.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

	Exubera ®	Insulin Lispro
STARTED	38	20
COMPLETED	6	3
NOT COMPLETED	32	17
Lack of Efficacy	3	0
Withdrawal by Subject	9	2
Related to study drug	15	12
Not related to study drug	5	3

	Exubera ®	Insulin Lispro	Total
Number of Participants [units: participants]	38	20	58
Age, Customized^[1] [units: participants]
18 - 44 years	22	13	35
45 - 64 years	14	6	20
>=65 years	2	1	3
Gender [units: participants]
Female	17	6	23
Male	21	14	35

[1]	Safety population.

Outcome Measures

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1. Primary:

Change From Baseline in Glycosylated Hemoglobin (HbA1c) Percent (%) [ At 52 weeks ]

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2. Secondary:

Percentage of Subjects Who Attained HbA1c Levels of <8%, <7%, <6.5%, and >=8% [ At 52 weeks ]

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3. Secondary:

Percentage of Subjects With Absolute Reduction in HbA1c Levels From Baseline of >0.5%, >0.7% and >1.0% [ At 52 weeks ]

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4. Secondary:

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. ]

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5. Secondary:

Change From Baseline in FPG [ At 52 weeks or last observation ]

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6. Secondary:

Change From Baseline in Fasting Blood Glucose Based on Glucometer Data and In-hospital Assessments [ To 52 weeks ]

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7. Secondary:

Change From Baseline in Post-prandial Blood Glucose Based on Glucometer Data and In-hospital Assessments [ To 52 weeks ]

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8. Secondary:

Change From Baseline in Insulin Antibody Levels [ At weeks 24 and 52 or last observation. ]

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9. Secondary:

Change From Baseline in Body Weight [ At weeks 12, 24, 36, and 52 or last observation. ]

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10. Secondary:

Change From Baseline in Body Mass Index [ At weeks 12, 24, 36, and 52 or last observation. ]

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11. Secondary:

Change From Baseline in Basal Insulin Doses [ To 52 weeks ]

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12. Secondary:

Change From Baseline in Prandial Insulin Doses [ To 52 weeks ]

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13. Secondary:

Blood Glucose Values From Baseline Determined by Home-monitored Blood Glucose (Subject Recorded Worksheet Values) [ To 52 weeks. ]

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14. Secondary:

Change in Fasting Lipids From Baseline [ At weeks 24 and 52 or last observation ]

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15. Other Pre-specified:

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 ]

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16. Other Pre-specified:

Subject Reported Quality of Life From Baseline as Determined From Phase V System Measurement [ At weeks 6, 24, and 52 or last observation ]

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Serious Adverse Events

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Other Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Exubera ®	Preprandial inhaled insulin regimen plus once daily (QD) administration of insulin glargine.
Insulin Lispro	Subcutaneous (SC) insulin regimen of pre-prandial insulin lispro and QD administration of insulin glargine.

Other Adverse Events

	Exubera ®	Insulin Lispro
Total, other (not including serious) adverse events
# participants affected	35	20
Blood and lymphatic system disorders
Lymphadenitis ^†^A # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Ear and labyrinth disorders
Vertigo ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Aphthous stomatitis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Dyspepsia ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Haemorrhoids ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Nausea ^† # participants affected / at risk	2/38 (5.26%)	1/20 (5.00%)
Vomiting ^† # participants affected / at risk	3/38 (7.89%)	2/20 (10.00%)
General disorders
Asthenia ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Chest pain ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Drug intolerance ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Fatigue ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Hunger ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Malaise ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Pyrexia ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Infections and infestations
Balanitis candida ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Ear infection ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Gastroenteritis ^† # participants affected / at risk	3/38 (7.89%)	1/20 (5.00%)
Gastrointestinal infection ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Influenza ^† # participants affected / at risk	2/38 (5.26%)	1/20 (5.00%)
Localised infection ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Nasopharyngitis ^† # participants affected / at risk	9/38 (23.68%)	7/20 (35.00%)
Onychomycosis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Pharyngitis ^† # participants affected / at risk	0/38 (0.00%)	2/20 (10.00%)
Respiratory tract infection ^† # participants affected / at risk	0/38 (0.00%)	2/20 (10.00%)
Respiratory tract infection viral ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Sinusitis ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Tooth abscess ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Tracheitis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Upper respiratory tract infection ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Vaginal candidiasis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Viral pharyngitis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Vulvovaginitis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Injury, poisoning and procedural complications
Eye injury ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Fall ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Joint sprain ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Thermal burn ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Wound ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Investigations
Alanine aminotransferase increased ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Weight decreased ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Weight increased ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Metabolism and nutrition disorders
Anorexia ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Hyperglycaemia ^† # participants affected / at risk	2/38 (5.26%)	1/20 (5.00%)
Hypoglycaemia ^† # participants affected / at risk	33/38 (86.84%)	18/20 (90.00%)
Polydipsia ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Back pain ^† # participants affected / at risk	2/38 (5.26%)	1/20 (5.00%)
Bone pain ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Joint swelling ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Musculoskeletal pain ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Myalgia ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Myositis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Neck pain ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Tendonitis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Nervous system disorders
Disturbance in attention ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Dizziness ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Headache ^† # participants affected / at risk	4/38 (10.53%)	1/20 (5.00%)
Somnolence ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Tremor ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Psychiatric disorders
Depression ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Disorientation ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Mental disorder ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Renal and urinary disorders
Ketonuria ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Polyuria ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Reproductive system and breast disorders
Endometriosis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^† # participants affected / at risk	5/38 (13.16%)	0/20 (0.00%)
Dyspnoea ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Hyperventilation ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Laryngeal oedema ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Pharyngolaryngeal discomfort ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Pharyngolaryngeal pain ^† # participants affected / at risk	2/38 (5.26%)	2/20 (10.00%)
Rhinitis allergic ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Rhinorrhoea ^† # participants affected / at risk	2/38 (5.26%)	0/20 (0.00%)
Throat irritation ^† # participants affected / at risk	4/38 (10.53%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Rash macular ^† # participants affected / at risk	0/38 (0.00%)	1/20 (5.00%)
Vascular disorders
Haematoma ^† # participants affected / at risk	1/38 (2.63%)	1/20 (5.00%)
Hot flush ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)
Hypertensive crisis ^† # participants affected / at risk	1/38 (2.63%)	0/20 (0.00%)

^†	Indicates events were collected by systematic assessment.
^A	Term from vocabulary, MedDRA (v11.0)

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of <60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), <12 mo from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
As a result of Pfizer’s decision to stop marketing Exubera ®, this study was terminated. Due to the early termination of the study and the low number of subjects who completed, no descriptive statistics for efficacy endpoints are provided.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com

No publications provided

Responsible Party:	Pfizer, Inc. ( Director, Clinical Trial Disclosure Group )
Study ID Numbers:	A2171035
Study First Received:	July 24, 2006
Results First Received:	June 24, 2009
Last Updated:	August 25, 2009
ClinicalTrials.gov Identifier:	NCT00356421 History of Changes
Health Authority:	United States: Food and Drug Administration