Efficacy and Safety Study of 4 Dose Regimens of Oral Alba... | NCT00730405

Name	Class
GlaxoSmithKline	INDUSTRY

Label	Type	Description	Intervention Names
Albaconazole 100mg	Active Comparator	Albaconazole for 36 weeks	Drug: Albaconazole 100mg
Albaconazole 200mg	Active Comparator	Albaconazole for 36 weeks	Drug: Albaconazole 200mg
Albaconazole 400mg	Active Comparator	Albaconazole for 36 weeks	Drug: Albaconazole 400mg
Albaconazole 400mg 24 weeks, Placebo 12 weeks	Active Comparator	Albaconazole for 24 weeks, Placebo for 12 weeks	Drug: Albaconazole 400mg Drug: Placebo 400 mg
Placebo 400 mg	Placebo Comparator	Placebo for 36 weeks	Drug: Placebo 400 mg

Name	Type	Description	Arm Group Labels	Other Names
Albaconazole 100mg	Drug	Albaconazole for 36 weeks	Albaconazole 100mg

Measure	Description	Time Frame
The Percentage of Participants Who Achieve Effective Treatment at Week 52	At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Effective treatment was defined as a mycological cure and clear or almost clear nail (distal subungual hyperkeratosis and/or onycholysis leaving less than 10% of nail plate effected). Comparisons were carried out in a sequential step-down fashion, combined with the Holm procedure at step 2. P-value was based on a sequential step-down combined with the Holm procedure. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52.	Week 52

Measure	Description	Time Frame
The Percentage of Participants Who Achieve Clinical Cure at Week 52	At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Clinical cure was defined as 100% clear nail. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject aged 18 to 75 years.
Diagnosis with distal subungual onychomycosis of the toenails that affects at least one great toe (target toenail).
Subject is willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol-specific procedures are performed.
Subject is able to complete the study, comply with study instructions, and take study product orally.
Sexually active non-lactating females of childbearing potential participating in the study must agree to use a medically acceptable method of contraception while receiving protocol-assigned product and up to the first menses 60 days following the last dose of study product.
Women of childbearing potential must have a negative pregnancy test at enrollment.
Subject has screening laboratory parameters and ECG within the normal ranges unless considered to be not clinically relevant by the principal investigator.

Exclusion Criteria:

Subjects with any of the following conditions or characteristics will be excluded from study enrollment (ie, will not receive study product):

Subject has received an investigational drug within 4 weeks of the first dose of study product, or who are scheduled to receive an investigational drug other than the study product during the study.
Subject has participated in a clinical trial for the systemic treatment of onychomycosis of the toenails within 6 months prior to the first dose of study product.
Subject is receiving any drugs that are known substrates of the 3A4 isozyme of cytochrome P450 (CYP3A4) with QT prolongation potential or any of the concomitant medications listed under prohibited medication section.
Subject has a history of known or suspected intolerance to albaconazole or the formulation excipients, or to azole antifungal drugs in general.
Subject has previously participated in a clinical study with albaconazole.
Subject is not prepared to give up use of any nail cosmetic products for the duration of the study.
Subject has any known immunodeficiency or history of malignancy in the last 4 years, excluding nonmelanoma skin cancer.
Subject has any known liver disease or a history of liver toxicity with other drugs.
Subject is currently suffering from any disease or condition, that could include abnormal laboratory tests, and/or who are currently using medication which in the opinion of the investigator may affect the evaluation of the study product or place the subject at undue risk.
Subject has psoriasis, lichen planus, or other abnormalities that could result in a clinically abnormal toenail.
Subject has a history of any condition that could possibly affect absorption of drug (eg, gastrectomy), uncontrolled diabetes, clinically significant peripheral vascular disease or peripheral circulatory impairment, or has had any major illness within 30 days prior to the screening examination.
Subject has a history of drug, prescription medicine, or alcohol abuse within the past 2 years.
Female subjects who are pregnant, trying to become pregnant, or lactating.
Employees of Investigator/clinical research organization (CRO) or Stiefel Laboratories, Inc., or an immediate family member (partner, offspring, parents, siblings or sibling's offspring) of an employee.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
Genova Clinical Research

PubMed Identifier	Type	Citation	Retractions
23706639	Background	Sigurgeirsson B, van Rossem K, Malahias S, Raterink K. A phase II, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study to investigate the efficacy and safety of 4 dose regimens of oral albaconazole in patients with distal subungual onychomycosis. J Am Acad Dermatol. 2013 Sep;69(3):416-25. doi: 10.1016/j.jaad.2013.03.021. Epub 2013 May 22.

Label	URL
Results for study 114554 can be found on the GSK Clinical Study Register.	View source

ID	Title	Description
FG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 milligrams (mg) of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.

Arm/Group Information

ID	Title	Description
BG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
BG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 24 weeks followed by 4 placebo capsules every week for 12 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
BG002	Albaconazole 200 mg (36 Weeks) Oral Weekly	Participants received 4 capsules (2 active + 2 placebo) containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
BG003	Albaconazole 100 mg (36 Weeks) Oral Weekly	Participants received 4 capsules (1 active + 3 placebo) containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
BG004	Placebo	Participants received 4 placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
BG005	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Percentage of Participants Who Achieve Effective Treatment at Week 52

At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Effective treatment was defined as a mycological cure and clear or almost clear nail (distal subungual hyperkeratosis and/or onycholysis leaving less than 10% of nail plate effected). Comparisons were carried out in a sequential step-down fashion, combined with the Holm procedure at step 2. P-value was based on a sequential step-down combined with the Holm procedure. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52.

The intent-to-treat (ITT) analysis set consists of all randomized participants who receive study product. All participants were available at the time of assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 52

ID	Title	Description
OG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 24 weeks followed by 4 placebo capsules every week for 12 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG002	Albaconazole 200 mg (36 Weeks) Oral Weekly	Participants received 4 capsules (2 active + 2 placebo) containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG003	Albaconazole 100 mg (36 Weeks) Oral Weekly	Participants received 4 capsules (1 active + 3 placebo) containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG004	Placebo	Participants received 4 placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.

Units	Counts
Participants	OG000116 OG001117 OG002117 OG003

Title

Denominators

Categories

Title	Measurements
	OG00054(45.2 to 63.4) OG00138(28.8 to 46.4) OG00229(20.8 to 37.3) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG004		Cochran-Mantel-Haenszel		<0.001														Superiority or Other
OG001 OG004		Cochran-Mantel-Haenszel		<0.001

Secondary

The Percentage of Participants Who Achieve Clinical Cure at Week 52

At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Clinical cure was defined as 100% clear nail. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52.

ITT analysis set. All participants were available at the time of assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 52

ID	Title	Description
OG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 24 weeks followed by 4 placebo capsules every week for 12 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.

Secondary

The Percentage of Participants Who Achieve Mycological Cure at Week 52

At each study visit, the investigator assessed the percentage of affected toenail on the target nail by estimating the percent affected nail in each quadrant, summing the percent affected in each quadrant and dividing the sum by 4. Mycological cure was defined as negative potassium hydroxide (KOH) and negative cultures for dermatophytes. It was assessed on Week 12, 16, 20, 24, 30, 36, 44 and 52.

ITT analysis set. All participants were available at the time of assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 52

ID	Title	Description
OG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.

Secondary

The Percentage of Participants Who Achieve Complete Cure at Week 52

ITT analysis set. All participants were available at the time of assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 52

ID	Title	Description
OG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 24 weeks followed by 4 placebo capsules every week for 12 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.

Secondary

Absolute Change in Unaffected Part of Target Nail From Baseline to Week 52

Length of the unaffected part of the target nail was measured in millimeters along the midpoint from the nail fold to the proximal border of the affected part (lowest point affected) along the midpoint of the target nail. It was assessed on Week 4, 8, 12, 16, 20, 24, 30, 36, 44 and 52. Baseline values were the observations at Week 0/Day 1 or before. Change from Baseline was a Baseline value subtracted from Week 52 value. P-value was based on analysis of variance (ANOVA) with treatment and pooled center. Statistics is provided for adjusted least square mean.

ITT analysis set. All participants were available at the time of assessment.

Posted

Mean

Standard Deviation

Millimeters

Baseline (Week 0/Day 1 or before) and up to Week 52

ID	Title	Description
OG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 24 weeks followed by 4 placebo capsules every week for 12 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.

Secondary

The Percentage of Participants With a Global Change Score of Cleared or Much Improved at Week 52

A count of the number of toenails affected, using visual examination, was performed at all study visits (Week 12, 24, 30, 36, 44 and 52). The investigator given a global evaluation of the toenails condition, based on the investigator's assessment of the reduction in extent of nail involvement and improvement in clinical signs as compared with the status at the Baseline visit. The 0-5 rating scale was used: 0: cleared, 1: much improved, 2: minimally improved, 3: unchanged, 4: minimally worse and 5: much worse; where higher score indicates worse condition and lower score indicates clear toenail.

ITT analysis set. All participants were available at the time of assessment.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 52

ID	Title	Description
OG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.
OG001	Albaconazole 400 mg (24 Weeks) Oral Weekly

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)
EG000	Albaconazole 400 mg (36 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.	0	116	4	116
EG001	Albaconazole 400 mg (24 Weeks) Oral Weekly	Participants received 4 capsules containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 24 weeks followed by 4 placebo capsules every week for 12 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.	1	117	7	117
EG002	Albaconazole 200 mg (36 Weeks) Oral Weekly	Participants received 4 capsules (2 active + 2 placebo) containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.	0	117	3	117
EG003	Albaconazole 100 mg (36 Weeks) Oral Weekly	Participants received 4 capsules (1 active + 3 placebo) containing 100 mg of albaconazole in combination with amino methacrylate copolymer as film coated microcrystalline cellulose spheres once every week for 36 weeks. Albaconazole film-coated spheres are filled in size 1, off white, hard gelatin capsules. Placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.	1	117	6	117
EG004	Placebo	Participants received 4 placebo capsules with identical ingredients and packaging as albaconazole capsules but without the active ingredient albaconazole. The capsules were swallowed whole with water, not chewed or crushed. Study product was administered every 7 days. Visits were scheduled on dosing days; dosing on visit dates was administered at the site.	0	115	2	115

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG0030 affected117 at risk EG0040 affected115 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0021 affected117 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Bronchitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0021 affected117 at risk EG003
Cellulitis	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Gastroenteritis salmonella	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Pneumonia	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Urosepsis	Infections and infestations	MedDRA version	Systematic Assessment	EG0002 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Wound infection	Infections and infestations	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Limb crushing injury	Injury, poisoning and procedural complications	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Traumatic brain injury	Injury, poisoning and procedural complications	MedDRA version	Systematic Assessment	EG0001 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0021 affected117 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Peripartum cardiomyopathy	Pregnancy, puerperium and perinatal conditions	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Depression	Psychiatric disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0001 affected116 at risk EG0010 affected117 at risk EG0020 affected117 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003
Abortion induced	Surgical and medical procedures	MedDRA version	Systematic Assessment	EG0000 affected116 at risk EG0011 affected117 at risk EG0020 affected117 at risk EG003

ID	Term
D014005	Tinea
D003881	Dermatomycoses
D009181	Mycoses
D001423	Bacterial Infections and Mycoses
D007239	Infections
D012874	Skin Diseases, Infectious
D009260	Nail Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases