A Clinical Trial Assessing The Impact Of Inhaled Insulin On Glucose Control In Patients With Type 2 Diabetes Mellitus

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00282971
• Collaborator: (none)
• Enrollment: 354
• Locations: 64
• Arms: 2
• Actual Duration (Months): 23.5
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the impact on glucose control by inhaled insulin in patients with type 2 diabetes who are not well controlled on 2 or more oral anti-diabetic agents

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2	Drug: Inhaled Insulin (Exubera); Other: Standard of Care	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 354 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Six Month, Open-label Outpatient, Parallel Group Trial Assessing The Impact Of Inhaled Insulin (Exubera(Registered)) On Glycemic Control In Patients With Type 2 Diabetes Mellitus Who Are Poorly Controlled On Two Oral Anti-diabetic Agents
• Actual Study Start Date: Mar 6, 2006
• Actual Primary Completion Date: Feb 19, 2008
• Actual Study Completion Date: Feb 19, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Insulin Inhaled insulin plus oral therapy	Drug: Inhaled Insulin (Exubera); Addition of inhaled insulin to pre-existing oral diabetes therapy.
Other: Standard of Care Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators	Other: Standard of Care; Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 [4, 12 and 24 weeks]

   [(week 24 value - baseline value)/baseline value]*100%

Secondary Outcome Measures

1. Percentage of Participants Achieving Glycemic Control by Visit [4, 12 and 24 weeks]

   2 definitions of good glycemic control were used: an HbA1c result of ≤6.5% or ≤7.0%

2. Change From Baseline in FEV1 at Week 24 LOCF [24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diabetes mellitus type 2

• Failing two or more oral anti-diabetic agents

Exclusion Criteria:

• Asthma, COPD

• Smoking

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gain Medical Center	Coquitlam	British Columbia	Canada	V3K 3P4
2	Misericordia Health Centre	Winnipeg	Manitoba	Canada	R3C 1A2
3	Maritime Research Center	Bathurst	New Brunswick	Canada	E2A 4X7
4	Office of Dr. Salim Sunderji	London	Ontario	Canada	N6P 1A9
5	Orillia Soldier's Memorial Hospital	Orillia	Ontario	Canada	L3V 2Z6
6	Douglas Tweel M.D. Professional Corporation	Charlottetown	Prince Edward Island	Canada	C1A 1L2
7	Laboratoire Sante Le Gaspesien Inc.	Bonaventure	Quebec	Canada	G0C 1E0
8	Centre de santé et de services sociaux de Chicoutimi, Centre de médecine genique communataire	Chicoutimi	Quebec	Canada	G7H 5H6
9	Rhodin Recherche Clinique	Drummondville	Quebec	Canada	J2B 1H8
10	Q & T Research Outaouais Inc.	Gatineau	Quebec	Canada	J8Y 6S9
11	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V2H1
12	Hopital Laval	Saint-Foy	Quebec	Canada	G1V 4G5
13	Centre Medical des Carrieres	St-Marc-des-Carrieres	Quebec	Canada	G0A 4B0
14	CIC Mauricie Inc.	Trois-Rivières	Quebec	Canada	G8T 7A1
15	Hotel Dieu CHU, Clinique d´Endocrinologie, Maladie Metaboliques, Nutrition	Nantes	Cedex 01	France	F-44035
16	Groupe Hospitalier Sud/Service d'Endocrinologie	Amiens cedex 1		France	80094
17	Private Practise	Armentieres		France	59427
18	Service d'Endocrinologie-	Bondy Cedex		France	93143
19	Hopital LA Cavale Blanche, Service de Diabetologie	Brest CEDEX		France	29609
20	CHU Cote de Nacre, Service d'Endocrinologie	Cean Cedex		France	14033
21	Private Practise	Chartres		France	28000
22	Office of Antoine Lemaire, MD	Lille		France	59000
23	Centre Hospitalier Bretagne Sud	Lorient Cedex		France	56322
24	Hopital Lapeyronnie Sce des Maladies	Montpellier CEDEX 5		France	34295
25	Hopital Bichat, Service d'Endocrinology	Paris Cedex 18		France	75877
26	Hopital Saint Michel	Paris		France	75015
27	Hopital Robert Debre	Reims		France	51100
28	C.H. Sud, Diabetologie	Rennes		France	35056
29	Centre Hospitalier Victor Provo	Roubaix		France	59100
30	Hôpital Jeanne d'Arc - Dommartin les Toul	Toul Cedex		France	54201
31	General Hospital of Athens "Laikon", 1st Propedeutic University Internal Medicine Clinic	Athens		Greece	11527
32	"Hygeia" Diagnostic and Therapeutic Center of Athens, Diabetes Clinic	Athens		Greece	151 23
33	"ATTIKON" University General Hospital, 2nd Propedeutic University Internal Medicine Clinic	Haidari		Greece	124 62
34	Peripheral General Hospital of Nikaia "Ag. Panteleimon", Internal Medicine Department	Pireaus		Greece	18454
35	University General Hospital of Thessaloniki "A.H.E.P.A." 1st Propedeutic University Internal Medicin	Thessaloniki		Greece	546 36
36	Hospital Infante D. Pedro	Aveiro		Portugal	3814-096
37	Hospitais da Universidade de Coimbra	Coimbra		Portugal	3000-075
38	Associação Protectora dos Diabéticos de Portugal	Lisboa		Portugal	1250-203
39	Serviço de Endocrinologia - Hospital de Egas Moniz	Lisboa		Portugal	1300
40	Hospital Geral de Santo António	Porto		Portugal	4099-001
41	Centro Hospitalar de Torres Vedras	Torres Vedras		Portugal	2560-324
42	Hospital Clinico Universitario de Santiago	Santiago de Compostela	A Coruña	Spain	15706
43	Hospital de Conxo	Santiago de Compostela	A Coruña	Spain	15706
44	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain	33006
45	Hospital de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	08907
46	Hospital Mutua de Terrassa	Terrassa	Barcelona	Spain	08221
47	Clinica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
48	Hospital General Universitario de Alicante	Alicante		Spain	03010
49	Hospital de La Santa Creu I Sant Pau	Barcelona		Spain	08025
50	Hospital General Universitario Valle de Hebron	Barcelona		Spain	08035
51	Hospital Universitario Puerta de Hierro	Madrid		Spain	28035
52	Hospital 12 de Octubre	Madrid		Spain	28041
53	Hospital de Mostoles	Madrid		Spain	28935
54	Complejo Hospitalario Carlos Haya Hospital Civil - Pabellon C	Malaga		Spain	29009
55	Hospital Montecelo	Pontevedra		Spain	36071
56	Hospital Universitario La Fe	Valencia		Spain	46009
57	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
58	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
59	Sodersjukhuset	Stockholm		Sweden	118 83
60	Karolinska US Huddinge	Stockholm		Sweden	141 86
61	Ängelholms sjukhus	Ängelholm		Sweden	262 81
62	Hacettepe University Medical School Department of Endocrinology	Anakara		Turkey
63	Istanbul University Istanbul Medical School, Department of Endocrinology	Istanbul		Turkey	34390
64	Dokuz Eylul University Medical School, Department of Endocrinology	Izmir		Turkey	35340

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00282971
• Other Study ID Numbers: A2171063; EXACTA; 2005-003504-11
• First Posted: Jan 27, 2006
• Last Update Posted: Apr 2, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pfizer: Type 2 diabetes melllitus
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin

Study Results

Participant Flow

Pre-assignment Detail	Total subjects enrolled=354. Total subjects given study drug=351. (ie, 3 subjects withdrew after enrollment/randomization, but prior to receiving study drug)

Arm/Group Title	Inhaled Insulin	Standard of Care
Arm/Group Description	Inhaled insulin plus oral therapy	Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators
Period Title: Overall Study
STARTED	180	171
COMPLETED	146	149
NOT COMPLETED	34	22

Baseline Characteristics

Arm/Group Title	Inhaled Insulin	Standard of Care	Total
Arm/Group Description	Inhaled insulin plus oral therapy	Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators	Total of all reporting groups
Overall Participants	180	171	351
Age, Customized (participants) [Number]
<18 years	0 0%	0 0%	0 0%
Between 18 and 44 years	12 6.7%	6 3.5%	18 5.1%
Between 45 and 64 years	112 62.2%	113 66.1%	225 64.1%
>=65 years	56 31.1%	52 30.4%	108 30.8%
Sex: Female, Male (Count of Participants)
Female	76 42.2%	80 46.8%	156 44.4%
Male	104 57.8%	91 53.2%	195 55.6%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
Description	[(week 24 value - baseline value)/baseline value]*100%
Time Frame	4, 12 and 24 weeks

Outcome Measure Data

Analysis Population Description

Out of 180 and 171 subjects that were treated with study drug and usual care, respectively, the Full Analysis Set (FAS)for each group which was analyzed for efficacy, was 179 and 170 subjects, respectively.

Arm/Group Title	Inhaled Insulin	Standard of Care
Arm/Group Description	Inhaled insulin plus oral therapy	Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators
Measure Participants	179	170
week 4 (n=164 and 158, respectively)	-1.08 (0.61)	-0.62 (0.55)
week 12 (n=159 and 150, respectively)	-2.03 (0.97)	-1.37 (0.92)
week 24 (n=142 and 150, respectively)	-2.02 (1.10)	-1.44 (1.10)
week 24 (LOCF, n=175 and 170, respectively)	-1.94 (1.09)	-1.42 (1.09)

2. Secondary Outcome

Title	Percentage of Participants Achieving Glycemic Control by Visit
Description	2 definitions of good glycemic control were used: an HbA1c result of ≤6.5% or ≤7.0%
Time Frame	4, 12 and 24 weeks

Outcome Measure Data

Analysis Population Description

Out of 180 and 171 subjects that were treated with study drug and usual care, respectively, the Full Analysis Set (FAS)for each group which was analyzed for efficacy, was 179 and 170 subjects, respectively. LOCF=last observation carried forward.

Arm/Group Title	Inhaled Insulin	Standard of Care
Arm/Group Description	Inhaled insulin plus oral therapy	Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators
Measure Participants	179	170
HbA1c<=7% at week 4 (n=165 and 158 respectively)	6.1 3.4%	0.0 0%
HbA1c<=7% at week 12 (n=160 and 150 respectively)	38.1 21.2%	11.3 6.6%
HbA1c<=7% at week 24 (n=143 and 150 respectively)	34.3 19.1%	12.0 7%
HbA1c<=7% at wk-24 LOCF (n=178 & 170 respectively)	32.0 17.8%	12.9 7.5%
HbA1c<=6.5% at week 4 (n=165 and 158 respectively)	0.6 0.3%	0.0 0%
HbA1c<=6.5% at week 12 (n=160 &150 respectively)	15.6 8.7%	4.7 2.7%
HbA1c<=6.5% at week 24 (n=143 &150 respectively)	18.2 10.1%	6.0 3.5%
HbA1c<=6.5% at wk-24 LOCF(n=178 &170 respectively)	15.2 8.4%	5.9 3.5%

3. Secondary Outcome

Title	Change From Baseline in FEV1 at Week 24 LOCF
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Out of 180 and 171 subjects that were treated with study drug and usual care, respectively, the Full Analysis Set (FAS)for each group which was analyzed for efficacy, was 179 and 170 subjects, respectively.FEV1=forced expiratory volume in 1 second;LOCF=last observation carried forward.

Arm/Group Title	Inhaled Insulin	Standard of Care
Arm/Group Description	Inhaled insulin plus oral therapy	Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators
Measure Participants	179	170
Mean (Standard Deviation) [Liter]	-0.27 (9.85)	-0.08 (0.61)

Adverse Events

Arm/Group Title	Inhaled Insulin		Standard of Care
Arm/Group Description	Inhaled insulin plus oral therapy		Standard of Care: All licensed diabetes drugs can be prescribed per discretion of investigators
All Cause Mortality
	Inhaled Insulin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Inhaled Insulin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/180 (4.4%)		6/171 (3.5%)
Cardiac disorders
Acute myocardial infarction	1/180 (0.6%)		0/171 (0%)
Cardiac failure	1/180 (0.6%)		0/171 (0%)
Coronary artery disease	0/180 (0%)		1/171 (0.6%)
Myocardial infarction	0/180 (0%)		1/171 (0.6%)
Gastrointestinal disorders
Pancreatitis acute	0/180 (0%)		1/171 (0.6%)
General disorders
Oedema peripheral	1/180 (0.6%)		0/171 (0%)
Hepatobiliary disorders
Cholecystitis	1/180 (0.6%)		0/171 (0%)
Infections and infestations
Incision site cellulitis	1/180 (0.6%)		0/171 (0%)
Injury, poisoning and procedural complications
Device malfunction	1/180 (0.6%)		0/171 (0%)
Investigations
Blood glucose increase	1/180 (0.6%)		0/171 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/180 (0%)		1/171 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/180 (0.6%)		1/171 (0.6%)
Prostate cancer	0/180 (0%)		1/171 (0.6%)
Nervous system disorders
Cerebrovascular accident	1/180 (0.6%)		0/171 (0%)
Transient ischaemic attack	0/180 (0%)		1/171 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/180 (0.6%)		0/171 (0%)
Other (Not Including Serious) Adverse Events
	Inhaled Insulin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	123/180 (68.3%)		98/171 (57.3%)
Gastrointestinal disorders
Abdominal pain	2/180 (1.1%)		4/171 (2.3%)
Diarrhoea	4/180 (2.2%)		3/171 (1.8%)
General disorders
Asthenia	5/180 (2.8%)		6/171 (3.5%)
Fatigue	4/180 (2.2%)		3/171 (1.8%)
Pyrexia	4/180 (2.2%)		1/171 (0.6%)
Infections and infestations
Bronchitis	5/180 (2.8%)		2/171 (1.2%)
Influenza	6/180 (3.3%)		7/171 (4.1%)
Nasopharyngitis	8/180 (4.4%)		4/171 (2.3%)
Upper respiratory tract infection	5/180 (2.8%)		5/171 (2.9%)
Urinary tract infection	7/180 (3.9%)		6/171 (3.5%)
Metabolism and nutrition disorders
Hypoglycaemia	118/180 (65.6%)		98/171 (57.3%)
Nervous system disorders
Dizziness	6/180 (3.3%)		3/171 (1.8%)
Headache	2/180 (1.1%)		6/171 (3.5%)
Tremor	8/180 (4.4%)		5/171 (2.9%)
Respiratory, thoracic and mediastinal disorders
Cough	10/180 (5.6%)		2/171 (1.2%)
Vascular disorders
Hypertension	2/180 (1.1%)		4/171 (2.3%)

Limitations/Caveats

Study terminated prematurely since the sponsor stopped marketing and manufacturing of EXUBERA and withdrew Market Authorization in Europe in September 2008. No efficacy, safety, or quality reason was associated with the premature halt of this study.

More Information

Certain Agreements

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

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.