Bioequivalence Study of Albendazole 400 mg Tablets in Chinese Population

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01755637
• Collaborator: (none)
• Enrollment: 56
• Locations: 2
• Arms: 2
• Duration (Months): 2
• Patients Per Site: 28
• Patients Per Site Per Month: 14

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the pharmacokinetic profiles of two Albendazole tablet formulations manufactured under the different granulation processes in healthy Chinese adult males.

Condition or Disease	Intervention/Treatment	Phase
Helminthiasis	Drug: Albendazole	Phase 1

Detailed Description

Due to the product manufacture process change in Albendazole oral formulation from ethanol based granulation process to aqua based granulation process, State Food and Drug Administration officially requested Tianjin Smith Kline and French Laboratories to carry out a Bioequivalence study to demonstrate bioequivalence between the manufacturing processes. This trial will be conducted to support the official requirement via the comparison of the pharmacokinetic profiles between both the drugs manufactured under the different processes.

After oral administration, Albendazole is quickly oxidized into its pharmacologically active metabolite, Albendazole sulphoxide (ABZ-SO. Due to extensive metabolism and limited absorption, plasma concentration of ABZ after oral administration was found to be too low to be measured. Thus, this trial will also compare the pharmacokinetic profiles of ABZ-SO manufactured using different solvents.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-dose, Two-centre, Randomized, Open-label, Two-way Crossover Bioequivalence Study of Two Kinds of AlbendazoleTablet Formulations in Healthy Chinese Adult Males
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Albendazole tablet (Aqua Based) Albendazole tablets 400 milligram (mg) manufactured under aqua based solvent condition taken orally with 200 millilitre (mL) of water as single dose treatment.	Drug: Albendazole; Albendazole tablets 400 mg
Active Comparator: Albendazole tablet (Alcohol Based) Albendazole tablets 400 mg manufactured under ethanol based solvent condition taken orally with 200 mL of water as single dose treatment.	Drug: Albendazole; Albendazole tablets 400 mg

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole. [Blood samples were collected pre-dose 0 hour (hr) and post dose 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   AUC (0-t) was evaluated using the trapezoid rule.

2. AUC [0-infinity (Inf)] of Albendazole [Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   AUC (0-inf) was evaluated using the trapezoid rule.

3. Maximum Observed Plasma Concentration [Cmaximum (Max)] of Albendazole [Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   Cmax was depicted from plasma concentration of Albendazole.

Secondary Outcome Measures

1. Time to Reach Maximum Plasma Concentration (Tmax) of Albendazole [Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   Tmax was time at which Cmax of Albendazole was reached.

2. AUC (0-t) of Active Metabolite - Albendazole Sulphoxide [Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   AUC (0-t) of Albendazole i.e. Albendazole sulphoxide was evaluated using the trapezoid rule.

3. AUC (0-inf) of Active Metabolite - Albendazole Sulphoxide [Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   AUC (0-inf) of Albendazole sulphoxide was evaluated using the trapezoid rule.

4. Cmax of Active Metabolite - Albendazole Sulphoxide [Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr]

   Cmax was depicted from plasma concentration of Albendazole.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male aged from 18 years up to 40 years (inclusive).

2. Body mass index within the range of 19-24kg/m^2.

3. Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination.

4. Negative for serum hepatitis B surface antigen, hepatitis C antibody and antibody of HIV.

Exclusion Criteria:

1. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.

2. Substance abuse: Recent history (within the last year) of alcohol or other substance abuse or failed to pass drugs of abuse screen and/or alcohol screen test.

3. Disease

4. Current or recurrent disease that could affect the action, absorption or distribution of the study medication or clinical or laboratory assessments (e.g. hepatic disorders, abnormal liver function tests, renal insufficiency, congestive heart failure);

5. Current or relevant previous history of serious, severe or unstable physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures;

6. History of gastrointestinal bleeding or peptic ulcer;

7. Asthma

8. History of liver disease

9. Medication

10. Use of any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to dosing

11. Current or regular use of any prescription or over-the-counter medication, any other ABZ containing products, and traditional Chinese medicine.

12. Smoking

13. Subjects who are current smokers or non-smokers of less than 3 months;

14. Prior (within seven days of dosing) or current use of any other nicotine containing products, including nicotine replacement therapy.

15. Blood

16. Blood donation ≥ 500 ml within 90 days before the first study session.

17. Plasma donation within the 90 days before the first study session.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Hospital of China Aerospace Corporation	Beijing	Beijing	China	100049
2	Tongji Hospital, Medical College Huazhong	Wuhan	Hubei	China	430030

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01755637
• Other Study ID Numbers: O7921353
• First Posted: Dec 24, 2012
• Last Update Posted: Jul 15, 2013
• Last Verified: May 1, 2013

• Additional relevant MeSH terms: Helminthiasis; Albendazole

Study Results

Participant Flow

Recruitment Details	Study was conducted at two clinical sites in China.
Pre-assignment Detail	Out of 123 screened participants, 54 did not meet the study criteria; 12 withdrew consent and one was lost to follow -up. Only 56 participants were randomized.

Arm/Group Title	Albendazole (Aqua) First, Then Albendazole (Alcohol)	Albendazole (Alcohol) First, Then Albendazole (Aqua)
Arm/Group Description	Participants were orally administered with 400 milligram (mg) Albendazole tablets manufactured under aqua based solvent condition as single dose treatment, followed by single dose treatment of 400 mg albendazole tablets manufactured under ethanol based solvent conditions. A wash-out period of 7 days was maintained between treatment periods.	Participants were orally administered with 400 mg Albendazole tablets manufactured under ethanol based solvent condition as single dose treatment followed by 400 mg aqua based albendazole tablets. A wash-out period of 7 days was maintained between treatment periods.
Period Title: Period 1
STARTED	28	28
COMPLETED	28	27
NOT COMPLETED	0	1
Period Title: Period 1
STARTED	28	27
COMPLETED	28	27
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Randomized Participants
Arm/Group Description	All randomized participants were evaluated for baseline measures
Overall Participants	56
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	24.21 (2.715)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	56 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time t [AUC(0-t)] of Albendazole.
Description	AUC (0-t) was evaluated using the trapezoid rule.
Time Frame	Blood samples were collected pre-dose 0 hour (hr) and post dose 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Missing data was not imputed for evaluation.

Arm/Group Title	Experimental: Albendazole Tablet (Aqua Based)	Reference: Albendazole Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 milligram (mg) Albendazole tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	55	55
Mean (Standard Deviation) [nanogram (ng).hr per milliliter (mL)]	54.82 (51.56)	48.07 (49.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The bioequivalence between the two products was concluded if the 90% CIs (based on log transformed data and anti-logged) for the ratio of the geometric means lie completely within the range 80%-125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean Ratio of treatments
	Estimated Value	114.37
	Confidence Interval	(2-Sided) 90%; 100.49 to 130.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio of experimental and reference product was determined by exponentiating least-squares means of log-transformed value.

2. Primary Outcome

Title	AUC [0-infinity (Inf)] of Albendazole
Description	AUC (0-inf) was evaluated using the trapezoid rule.
Time Frame	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Missing data was not imputed for evaluation.

Arm/Group Title	Experimental: Albendazole Tablet (Aqua Based)	Reference: Albendazole Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 mg Albendazole tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	19	16
Mean (Standard Deviation) [ng.hr/mL]	69.55 (80.44)	67.19 (84.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The bioequivalence between the two products was concluded if the 90% CIs (based on log transformed data and anti-logged) for the ratio of the geometric means lie completely within the range 80%-125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio of treatments
	Estimated Value	107.41
	Confidence Interval	(2-Sided) 90%; 69.03 to 167.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio of experimental and reference product was determined by exponentiating least-squares means of log-transformed value.

3. Primary Outcome

Title	Maximum Observed Plasma Concentration [Cmaximum (Max)] of Albendazole
Description	Cmax was depicted from plasma concentration of Albendazole.
Time Frame	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Missing data was not imputed for evaluation.

Arm/Group Title	Experimental: Albendazole Tablet (Aqua Based)	Reference: Albendazole Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 milligram (mg) Albendazole tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	55	56
Mean (Standard Deviation) [ng/mL]	14.76 (15.88)	14.58 (16.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The bioequivalence between the two products was concluded if the 90% CIs (based on log transformed data and anti-logged) for the ratio of the geometric means lie completely within the range of 70% -143%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio of treatments
	Estimated Value	111.28
	Confidence Interval	(2-Sided) 90%; 94.76 to 130.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio of experimental and reference product was determined by exponentiating least-squares means of log-transformed value.

4. Secondary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Albendazole
Description	Tmax was time at which Cmax of Albendazole was reached.
Time Frame	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Participants were excluded where the baseline concentration was greater than 5% of Cmax.

Arm/Group Title	Experimental: Albendazole Tablet (Aqua Based)	Reference: Albendazole Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 milligram (mg) Albendazole tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	55	56
Median (Full Range) [hr]	1.50	1.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The null hypothesis considered that there is no median within-subject difference between two treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Wilcoxon signed rank test
	Comments	The values were not adjusted for this non-parametric analysis.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.0167
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The median difference was calculated as = (Experimental-Reference)

5. Secondary Outcome

Title	AUC (0-t) of Active Metabolite - Albendazole Sulphoxide
Description	AUC (0-t) of Albendazole i.e. Albendazole sulphoxide was evaluated using the trapezoid rule.
Time Frame	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Participants were excluded where the baseline concentration was greater than 5% of Cmax.

Arm/Group Title	Experimental: Albendazole Sulphoxide Tablet (Aqua Based)	Reference: Albendazole Sulphoxide Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 milligram (mg) Albendazole sulphoxide tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole sulphoxide tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	55	55
Mean (Standard Deviation) [ng.hr/mL]	2563.90 (1108.19)	2290.14 (944.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The bioequivalence between the two products was concluded if the 90% CIs (based on log transformed data and anti-logged) for the ratio of the geometric means lie completely within the range 80%-125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio of treatments
	Estimated Value	112.05
	Confidence Interval	(2-Sided) 90%; 103.65 to 121.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio of experimental and reference product was determined by exponentiating least-squares means of log-transformed value.

6. Secondary Outcome

Title	AUC (0-inf) of Active Metabolite - Albendazole Sulphoxide
Description	AUC (0-inf) of Albendazole sulphoxide was evaluated using the trapezoid rule.
Time Frame	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Participants were excluded where the baseline concentration was greater than 5% of Cmax.

Arm/Group Title	Experimental: Albendazole Sulphoxide Tablet (Aqua Based)	Reference: Albendazole Sulphoxide Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 mg Albendazole sulphoxide tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole sulphoxide tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	43	45
Mean (Standard Deviation) [ng.hr/mL]	3263.88 (1456.41)	2829.77 (1128.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The bioequivalence between the two products was concluded if the 90% CIs (based on log transformed data and anti-logged) for the ratio of the geometric means lie completely within the range 80%-125%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio of treatments
	Estimated Value	113.10
	Confidence Interval	(2-Sided) 90%; 103.40 to 123.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio of experimental and reference product was determined by exponentiating least-squares means of log-transformed value.

7. Secondary Outcome

Title	Cmax of Active Metabolite - Albendazole Sulphoxide
Description	Cmax was depicted from plasma concentration of Albendazole.
Time Frame	Blood samples were collected pre-dose at 0 hr and post dose at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 16, 24 and 36 hr

Outcome Measure Data

Analysis Population Description

The analysis was carried out per protocol population. Missing data was not imputed for evaluation.

Arm/Group Title	Experimental: Albendazole Sulphoxide Tablet (Aqua Based)	Reference: Albendazole Sulphoxide Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 milligram (mg) Albendazole Sulphoxide tablets manufactured under aqua based solvent condition as single dose treatment.	Participants were orally administered with 400 mg Albendazole Sulphoxide tablets manufactured under ethanol based solvent condition as single dose treatment.
Measure Participants	55	56
Mean (Standard Deviation) [ng/mL]	221.45 (105.87)	199.99 (108.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Albendazole Tablet (Aqua Based), Reference: Albendazole Tablet (Alcohol Based)
	Comments	The value was log-transformed and a linear mixed effects model was applied to this value, as the dependent variable, treatment, and period as fixed effects and participants as random effect.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The bioequivalence between the two products was concluded if the 90% CIs (based on log transformed data and anti-logged) for the ratio of the geometric means lie completely within the range of 70% -143%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio of treatments
	Estimated Value	114.33
	Confidence Interval	(2-Sided) 90%; 102.99 to 126.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric mean ratio of experimental and reference product was determined by exponentiating least-squares means of log-transformed value.

Adverse Events

Time Frame	Adverse Events were collected from the first dosage of the session one, and until 5 days following last administration of the investigational product.
Arm/Group Title	Albendazole Tablet (Aqua Based)		Albendazole Tablet (Alcohol Based)
Arm/Group Description	Participants were orally administered with 400 mg Albendazole tablets manufactured under aqua based solvent condition as single dose treatment.		Participants were orally administered with 400 mg Albendazole tablets manufactured under ethanol based solvent condition as single dose treatment.
All Cause Mortality
	Albendazole Tablet (Aqua Based)		Albendazole Tablet (Alcohol Based)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Albendazole Tablet (Aqua Based)		Albendazole Tablet (Alcohol Based)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Albendazole Tablet (Aqua Based)		Albendazole Tablet (Alcohol Based)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/55 (1.8%)		4/56 (7.1%)
Gastrointestinal disorders
Diarrhoea	0/55 (0%)	0	1/56 (1.8%)	1
Infections and infestations
Urinary Tract Infection	1/55 (1.8%)	1	0/56 (0%)	0
Investigations
Gamma-Glutamyl Transferase Increased	0/55 (0%)	0	1/56 (1.8%)	1
Metabolism and nutrition disorders
Hyperuricaemia	0/55 (0%)	0	1/56 (1.8%)	1
Renal and urinary disorders
Albuminuria	0/55 (0%)	0	1/56 (1.8%)	1

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.