Rosiglitazone-Metformin Combination Versus Metformin-Sulfonylurea Combination On Beta-Cell Function In Type 2 Diabetes

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00367055
• Collaborator: (none)
• Enrollment: 84
• Duration (Months): 48

Study Details

Study Description

Brief Summary

It has been shown in previous study that progressive glycemic deterioration was associated with progressive loss of b-cell function, measured by the decrease in plasma insulin levels, irrespective of the therapy used (diet, sulfonylureas or metformin).There is growing evidence that thiazolidinediones could have a positive action on the b-cell function. But it has not yet been demonstrated that they could protect from a deterioration in insulin secretion in the long term. So, it appears interesting to study the long term evolution of the b-cell function and the possible protection with rosiglitazone in patients with type 2 diabetes showing evidence of loss of b-cell function with metformin alone.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: rosiglitazone-metformin; Drug: Metformin; Drug: metformin+ gliclazide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of the Action of the Rosiglitazone-metformin Fixed-dose Combination and of a Metformin-sulfonylurea Free Combination on the B-cell Function in Type 2 Diabetic Patients Not Controlled With Metformin Alone.
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Outcome Measures

Primary Outcome Measures

1. Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment [Baseline and Month 36]

   Change from baseline in the insulin secretory capacity was measured by the assesment of blood insulin concentrations (conc.) using the hyperglycaemic clamp (HC) technique, per intravenous glucose perfusion by a catheter. Change from baseline for insulin conc peaks (highest conc level) was calculated as the Month 36 value minus the baseline value. Insulin secretion was assessed by calculating AUC during the first 10 minutes of HC (incremental and total AUC0-10 min) and the AUC after the first 10 minutes of the HC (10-180min).

Secondary Outcome Measures

1. Median Change From Baseline in the Ratio M/I After a 36-month Treatment [Baseline and Month 36]

2. Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment [Baseline and Month 18]

   Change from baseline was calculated as the Month 18 value minus the baseline value. Insulin secretion capacity is measured in blood (blood level of insulin) and is a response of the pancreatic beta-cells to hyperglycemia induced by a glucose IV bolus, then infusion. Hyperglycemic clamp (HC) is a reference technique to evaluate the initial and the secondary phases of insulin secretion.

3. Mean Change From Baseline in HbA1c at Month 36 [Baseline and Month 36]

   Change from baseline was calculated as the Month 36 value minus the baseline value. HbA1c levels were measured by blood draw.

4. Mean Change From Baseline in FBG at Month 36 [Baseline and Month 36]

   Change from baseline was calculated as the Month 36 value minus the baseline value. FBG levels were measured by blood draw.

5. Median Change From Baseline in Insulin Resistance Index (HOMA-IR) After a 36-month Treatment [Baseline and Month 36]

6. Median Change From Baseline in Beta Cell Function Index (HOMA-beta) After a 36-month Treatment [Baseline and Month 36]

7. Mean Change From Baseline in CPP Total and Incremental AUC T0-T30 After a 36-month Treatment [Baseline and Month 36]

8. Mean Change From Baseline in CPP Concentration Peak and Incremental Concentration Peak T0-T30 After a 36-month Treatment [Baseline and Month 36]

9. Mean Change From Baseline in Insulin Sensitivity Index at Months 18 and 36 [Baseline and Months 18 and 36]

   Change from baseline was calculated as the Month 18 and 36 values minus the baseline value. Insulin sensitivity is measured as the quantity of glucose metabolized per unit of plasma insulin concentration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• Males and females 40 to 75 years of age (inclusive at the time of screening)

• Type 2 diabetes mellitus as defined by the WHO criteria, diagnosed for at least 1 year

• Subjects receiving 1.5 to 3g of metformin alone at a constant dose for at least 8 weeks prior to visit 1

• Patients with 6.5% < HbA1c > 8% at visit 1 and visit 2

• 25 < BMI < 35

EXCLUSION CRITERIA:

• Patient with type 1 diabetes

• Treatment with other hypoglycaemic agents than metformin in the last 3 months

• FPG >200 mg/dL at visit 2

• Hypersensitivity to the studied treatments (rosiglitazone, metformin chlorhydrate, gliclazide)

• Congestive heart failure (NYHA class I to IV), unstable or severe angina, recent myocardial infarction

• Respiratory insufficiency

• Subjects who have required the use of insulin for glycaemic control in the past 6 months prior to visit 1 (except during pregnancy or acute episodes such as hospitalization, trauma or infection) or subjects with a history of metabolic acidosis including diabetic ketoacidosis

• Anemia defined by haemoglobin concentration <11.0 g/dL for males and <10.0 g/dL for females

• Renal disease or renal dysfunction, e.g. as suggested by serum creatinine levels ≥135.0 µmol/L in males and ≥110.0 µmol/L in females and/or creatinine clearance <40 mL/min

• Presence of clinically significant hepatic disease, with ALT, AST, total bilirubin, alkaline phosphatase >2.5 times the upper limit of the normal reference range

• Subjects with chronic diseases requiring periodic ot intermittent treatment with oral or IV corticosteroids

• Subjects receiving danazol, miconazole or phenylbutazone

• Active alcohol, drug or medication abuse within the last 6 months or any condition that would indicate the likelihood of poor subject compliance

• Women who are lactating, pregnant or planning to become pregnant

• Any clinically significant abnormality identified at screening which, in the investigator's judgement, makes the subject unsuitable for inclusion in the study

• Use of any other investigational agent within 30 days or 5 half-lives (whichever is longer) prior to visit 1

• Subjects who receive or anticipate receiving radiocontrast dye during the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, MD, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00367055
• Other Study ID Numbers: 101765; AVAF4001
• First Posted: Aug 22, 2006
• Last Update Posted: Jul 27, 2010
• Last Verified: Jul 1, 2010

• Keywords provided by , ,: Beta cell function; Type 2 diabetes; Combination treatment
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Metformin; Rosiglitazone; Gliclazide

Study Results

Participant Flow

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
Period Title: Overall Study
STARTED	43	41
COMPLETED	32	30
NOT COMPLETED	11	11

Baseline Characteristics

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day	Total
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months	Total of all reporting groups
Overall Participants	43	41	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.3 (8.4)	58.1 (8.0)	58.2 (8.2)
Sex: Female, Male (Count of Participants)
Female	11 25.6%	16 39%	27 32.1%
Male	32 74.4%	25 61%	57 67.9%
Body Mass Index (BMI) (kilograms per square meter (kg/m2)) [Number]
<25	3	0	3
25-30	21	20	41
>30	19	21	40
FBG (Millimoles/Liter (mmol/L)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimoles/Liter (mmol/L)]	9.10 (1.72)	8.28 (1.11)	8.70 (1.50)
HbA1c (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	7.5 (0.55)	7.3 (0.55)	7.4 (0.57)

Outcome Measures

1. Primary Outcome

Title	Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment
Description	Change from baseline in the insulin secretory capacity was measured by the assesment of blood insulin concentrations (conc.) using the hyperglycaemic clamp (HC) technique, per intravenous glucose perfusion by a catheter. Change from baseline for insulin conc peaks (highest conc level) was calculated as the Month 36 value minus the baseline value. Insulin secretion was assessed by calculating AUC during the first 10 minutes of HC (incremental and total AUC0-10 min) and the AUC after the first 10 minutes of the HC (10-180min).
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: participants receiving at least one dose of study drug with an available efficacy evaluation (HC at M18 or M36). The measurement was conducted on participants who had baseline and M18 and M36 HC test data available. Each HC was validated at both Baseline and Month 36, resulting in different "n"s for each category.

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
Measure Participants	27	29
Total AUC(0-10 min), n=24, 26	-3.9	-75.3
Incremental AUC(0-10 min), n=22, 23	7.0	74.6
Total concentration peak(0-10 min), n=25, 26	-8.6	3.6
Incremental concentration peak(0-10 min), n=24, 26	-1.8	10.8
Total AUC(10-180 min), n=20, 24	40.6	-21.2
Incremental AUC(10-180 min), n=19, 24	67.0	13.6
Total concentration peak(10-180 min), n=27, 29	7.9	-9.3
Incremental concentation peak(10-180 min), n=25,29	10.8	11.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosiglitazone + Metformin 4 mg/2 g/Day, Gliclazide + Metformin 80 mg/2 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.376
	Comments	p value is for Total AUC(0-10 min)
	Method	Van Elteren
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rosiglitazone + Metformin 4 mg/2 g/Day, Gliclazide + Metformin 80 mg/2 g/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.990
	Comments	p value is for Incremental AUC(0-10 min)
	Method	Van Elteren
	Comments

2. Secondary Outcome

Title	Median Change From Baseline in the Ratio M/I After a 36-month Treatment
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment
Description	Change from baseline was calculated as the Month 18 value minus the baseline value. Insulin secretion capacity is measured in blood (blood level of insulin) and is a response of the pancreatic beta-cells to hyperglycemia induced by a glucose IV bolus, then infusion. Hyperglycemic clamp (HC) is a reference technique to evaluate the initial and the secondary phases of insulin secretion.
Time Frame	Baseline and Month 18

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: participants receiving at least one dose of study drug with an available efficacy evaluation (HC at M18 or M36). The measurement was conducted on participants who had baseline and M18 and M36 HC test data available. Each HC was validated at both Baseline and Month 36, resulting in different "n"s for each category.

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
Measure Participants	30	31
HC, Total AUC(0-10min), n=30, 31	18.3	-32.3
HC, Incremental AUC(0-10min), n=27, 26	22.3	60.7
HC, Total AUC(10-180min), n=26, 30	55.9	-7.6
HC, Incremental AUC(10-180min), n=26, 29	72.9	14.6
Arginine (Arg) test, Total AUC(0-30min), n=25, 25	38.4	10.9
Arg test, Incremental AUC(0-30min), n=25, 25	15.1	-8.0
Arg test, Incremental Conc. peak(0-30 min),n=26,29	23.3	-111.1

4. Secondary Outcome

Title	Mean Change From Baseline in HbA1c at Month 36
Description	Change from baseline was calculated as the Month 36 value minus the baseline value. HbA1c levels were measured by blood draw.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug and had an available efficacy evaluation (hyperglycaemic clamp at M18 or M36). This measurement was conducted on participants in the ITT Population who had baseline and M18 and M36 clamp test data available.

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
Measure Participants	32	31
Mean (Standard Deviation) [percent change]	-0.22 (1.3)	0.3 (1.2)

5. Secondary Outcome

Title	Mean Change From Baseline in FBG at Month 36
Description	Change from baseline was calculated as the Month 36 value minus the baseline value. FBG levels were measured by blood draw.
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug and had an available efficacy evaluation (hyperglycaemic clamp at M18 or M36). This measurement was conducted on participants in the ITT Population who had baseline and M18 and M36 clamp test data available.

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
Measure Participants	32	30
Mean (Standard Deviation) [millimoles per Liter (mmol/L)]	-1.6 (1.9)	-0.2 (2.4)

6. Secondary Outcome

Title	Median Change From Baseline in Insulin Resistance Index (HOMA-IR) After a 36-month Treatment
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Median Change From Baseline in Beta Cell Function Index (HOMA-beta) After a 36-month Treatment
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Mean Change From Baseline in CPP Total and Incremental AUC T0-T30 After a 36-month Treatment
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Mean Change From Baseline in CPP Concentration Peak and Incremental Concentration Peak T0-T30 After a 36-month Treatment
Time Frame	Baseline and Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Mean Change From Baseline in Insulin Sensitivity Index at Months 18 and 36
Description	Change from baseline was calculated as the Month 18 and 36 values minus the baseline value. Insulin sensitivity is measured as the quantity of glucose metabolized per unit of plasma insulin concentration.
Time Frame	Baseline and Months 18 and 36

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day	Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks	Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
Measure Participants	30	33
Month 18	-0.00511 (0.03451)	-0.02045 (0.05302)
Month 36	0.00040 (0.04722)	-0.01702 (0.05109)

Adverse Events

Arm/Group Title	Rosiglitazone + Metformin 4 mg/2 g/Day		Gliclazide + Metformin 80 mg/2 g/Day
Arm/Group Description	Initial dose of rosiglitazone + metformin of 4 milligrams (mg)/2 grams (g)/day; allowed adjustment of up to 8 mg/2 g/day after 8 weeks		Initial dose of gliclazide + metformin 80 mg/2 g/day; allowed adjustment of up to 160 mg/2 g/day after 4 weeks, up to 240 mg/2 g/day after 8 weeks, up to 320 mg/2 g/day after 3 months
All Cause Mortality
	Rosiglitazone + Metformin 4 mg/2 g/Day		Gliclazide + Metformin 80 mg/2 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rosiglitazone + Metformin 4 mg/2 g/Day		Gliclazide + Metformin 80 mg/2 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/43 (18.6%)		12/41 (29.3%)
Cardiac disorders
Myocardial ischemia	1/43 (2.3%)		0/41 (0%)
Congenital, familial and genetic disorders
Hydrocele	0/43 (0%)		1/41 (2.4%)
Gastrointestinal disorders
Oedematous pancreatitis	0/43 (0%)		1/41 (2.4%)
Inguinal hernia	1/43 (2.3%)		0/41 (0%)
Pancreatitis acute on chronic	1/43 (2.3%)		0/41 (0%)
Partial bowel obstruction	0/43 (0%)		1/41 (2.4%)
Proctorrhagia	0/43 (0%)		1/41 (2.4%)
Sigmoiditis	1/43 (2.3%)		0/41 (0%)
Umbilical hernia	0/43 (0%)		1/41 (2.4%)
General disorders
Asthenia	0/43 (0%)		1/41 (2.4%)
Hepatobiliary disorders
Biliary colic	1/43 (2.3%)		0/41 (0%)
Injury, poisoning and procedural complications
Wrist fracture	0/43 (0%)		1/41 (2.4%)
Metabolism and nutrition disorders
Anorexia	0/43 (0%)		1/41 (2.4%)
Hyperglycemia	0/43 (0%)		1/41 (2.4%)
Musculoskeletal and connective tissue disorders
Coxarthrosis	1/43 (2.3%)		0/41 (0%)
Gonarthrosis	1/43 (2.3%)		0/41 (0%)
Herniated disc	1/43 (2.3%)		0/41 (0%)
Spinal column stenosis	0/43 (0%)		1/41 (2.4%)
Trigger finger	0/43 (0%)		1/41 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Peritoneal carcinomatosis	0/43 (0%)		2/41 (4.9%)
Nervous system disorders
Carpal tunnel syndrome	0/43 (0%)		1/41 (2.4%)
Hemiplegia	0/43 (0%)		1/41 (2.4%)
Stroke	0/43 (0%)		1/41 (2.4%)
Renal and urinary disorders
Urinary incontinence aggravated	1/43 (2.3%)		0/41 (0%)
Urinary tract infection	1/43 (2.3%)		0/41 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/43 (0%)		3/41 (7.3%)
Vascular disorders
Digital necrosis	1/43 (2.3%)		0/41 (0%)
Femoral artery occlusion	1/43 (2.3%)		0/41 (0%)
Thrombophlebitis	0/43 (0%)		1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Rosiglitazone + Metformin 4 mg/2 g/Day		Gliclazide + Metformin 80 mg/2 g/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/43 (72.1%)		29/41 (70.7%)
Ear and labyrinth disorders
Vertigo	1/43 (2.3%)		3/41 (7.3%)
Gastrointestinal disorders
Diarrhea	3/43 (7%)		3/41 (7.3%)
Constipation	2/43 (4.7%)		1/41 (2.4%)
Sigmoiditis	2/43 (4.7%)		1/41 (2.4%)
Colopathy	2/43 (4.7%)		0/41 (0%)
Nausea	2/43 (4.7%)		0/41 (0%)
Abdominal pain	1/43 (2.3%)		2/41 (4.9%)
Infections and infestations
Tonsilitis	1/43 (2.3%)		2/41 (4.9%)
Fungal infection	0/43 (0%)		3/41 (7.3%)
Rhinitis	0/43 (0%)		3/41 (7.3%)
Orchitis	0/43 (0%)		2/41 (4.9%)
Metabolism and nutrition disorders
Hypoglycemia	1/43 (2.3%)		8/41 (19.5%)
Hyperglycemia	1/43 (2.3%)		2/41 (4.9%)
Musculoskeletal and connective tissue disorders
Lumbago	4/43 (9.3%)		1/41 (2.4%)
Lumbar pain	3/43 (7%)		2/41 (4.9%)
Knee pain	2/43 (4.7%)		3/41 (7.3%)
Gonalgia	2/43 (4.7%)		2/41 (4.9%)
Gonarthrosis	2/43 (4.7%)		1/41 (2.4%)
Tendonitis	1/43 (2.3%)		4/41 (9.8%)
Nervous system disorders
Carpal tunnel syndrome	1/43 (2.3%)		4/41 (9.8%)
Sciatica	3/43 (7%)		2/41 (4.9%)
Headache	3/43 (7%)		1/41 (2.4%)
Formication	0/43 (0%)		2/41 (4.9%)
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis	9/43 (20.9%)		3/41 (7.3%)
Bronchitis	8/43 (18.6%)		1/41 (2.4%)
Cough	3/43 (7%)		0/41 (0%)
Common cold	2/43 (4.7%)		0/41 (0%)
Pharyngitis	2/43 (4.7%)		2/41 (4.9%)
Sinusitis	2/43 (4.7%)		0/41 (0%)
Pulmonary embolism	0/43 (0%)		2/41 (4.9%)
Skin and subcutaneous tissue disorders
Eczema	0/43 (0%)		2/41 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.