Efficacy, Safety and Tolerability of Everolimus in Preven... | NCT00414440

ID	Type	Description	Link
2006-001485-16

Status Module

Label	Type	Description	Intervention Names
Everolimus	Experimental	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).	Drug: Everolimus
Placebo	Placebo Comparator	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	placebo comparator	Placebo
Everolimus

Measure	Description	Time Frame
Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation)	Everolimus (RAD001) compared to placebo with respect to the change from baseline in total kidney volume at Month 24.	Baseline, Month 24

Measure	Description	Time Frame
Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60	Course of calculated GFR (mL/min/1.73 m^2) at Months 24, 36, 48 and 60	Months 24, 36, 48 and 60
Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR

Eligibility Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Innsbruck		INNSBRUCK	Austria
Novartis Investigative Site

PubMed Identifier	Type	Citation	Retractions
39356039	Derived	St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
20581392	Derived

ID	Title	Description
FG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
FG001	Placebo

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

Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation)

Everolimus (RAD001) compared to placebo with respect to the change from baseline in total kidney volume at Month 24.

mITT set

Posted

Mean

95% Confidence Interval

Baseline, Month 24

ID	Title	Description
OG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
OG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

Units	Counts
Participants	OG000214 OG001217

Title

Denominators

Categories

Title	Measurements
	OG000230.1(172.4 to 287.9) OG001300.8(247.5 to 354.1)

Secondary

Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60

Course of calculated GFR (mL/min/1.73 m^2) at Months 24, 36, 48 and 60

ITT

Posted

Mean

Standard Deviation

mL/min/1.73 m^2

Months 24, 36, 48 and 60

ID	Title	Description
OG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
OG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

Units	Counts
Participants	OG000

Secondary

Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR

Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.

ITT

Posted

Mean

Standard Deviation

mL/min/1.73 m^2

Months 24, 36, 48 and 60

ID	Title	Description
OG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
OG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

Secondary

Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), at baseline and then months 12 and 24

ITT, observed cases

Posted

Mean

Standard Deviation

mmHG

Baseline, Months 12 and 24

mean

Participants

ID	Title	Description
OG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
OG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

Units	Counts
Participants	OG000

Secondary

Calculated GFR (mL/Min/1.73 m^2), Change From Baseline by Visit

Change in renal function was assessed by the Glomerular Filtration Rate (GFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.

ITT set, observed cases

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Months 3, 6, 9, 12, 18 and 24

calculated GFR

Participants

ID	Title	Description
OG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
OG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
IRON DEFICIENCY ANAEMIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
LEUKOCYTOSIS	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
LYMPH NODE PAIN	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
LYMPHADENOPATHY	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ANGINA PECTORIS	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
ATRIAL FLUTTER	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
BRADYARRHYTHMIA	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
BRADYCARDIA	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CARDIAC FAILURE	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CARDIOGENIC SHOCK	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CORONARY ARTERY DISEASE	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0013 affected217 at risk
LEFT VENTRICULAR FAILURE	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
MITRAL VALVE INCOMPETENCE	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
MYOPERICARDITIS	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PERICARDIAL EFFUSION	Cardiac disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
POLYCYSTIC LIVER DISEASE	Congenital, familial and genetic disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
ACUTE VESTIBULAR SYNDROME	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
VERTIGO	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
GOITRE	Endocrine disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
RETINAL DETACHMENT	Eye disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0011 affected217 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0011 affected217 at risk
ABDOMINAL TENDERNESS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
APHTHOUS STOMATITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
ASCITES	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
COLITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
COLONIC POLYP	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CROHN'S DISEASE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected214 at risk EG0011 affected217 at risk
GASTRIC HAEMORRHAGE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
GASTRITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
GASTRODUODENITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
HAEMORRHOIDAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
INGUINAL HERNIA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0014 affected217 at risk
OESOPHAGITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
RECTAL HAEMORRHAGE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
SUBILEUS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
UMBILICAL HERNIA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected214 at risk EG0012 affected217 at risk
VOMITING	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ASTHENIA	General disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0012 affected217 at risk
BLOODY DISCHARGE	General disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
CHEST PAIN	General disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
DISEASE PROGRESSION	General disorders	MedDRA	Systematic Assessment	EG0004 affected214 at risk EG0012 affected217 at risk
DRUG WITHDRAWAL SYNDROME	General disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
OEDEMA	General disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PYREXIA	General disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
CHOLECYSTITIS	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
HEPATIC CYST	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
HEPATIC CYST RUPTURED	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
HEPATOMEGALY	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PORTAL VEIN THROMBOSIS	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ANAPHYLACTIC SHOCK	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
HOUSE DUST ALLERGY	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
HYPERSENSITIVITY	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ACUTE TONSILLITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ANOGENITAL WARTS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
APPENDICITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
BRONCHITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
DIVERTICULITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
ENTEROCOLITIS INFECTIOUS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ERYSIPELAS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
GASTROENTERITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected214 at risk EG0010 affected217 at risk
GASTROINTESTINAL INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
HEPATIC CYST INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
HERPES SIMPLEX	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
HERPES ZOSTER	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
HERPES ZOSTER OPHTHALMIC	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
LYMPH NODE TUBERCULOSIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
LYMPHADENITIS BACTERIAL	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
OTITIS MEDIA CHRONIC	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PAPILLOMA VIRAL INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
PNEUMONIA	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected214 at risk EG0011 affected217 at risk
PYELONEPHRITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0012 affected217 at risk
PYELONEPHRITIS ACUTE	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
RENAL CYST INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0014 affected217 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0012 affected217 at risk
SINUSITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
UROSEPSIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
VESTIBULAR NEURONITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
VIRAL INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
ARTHROPOD STING	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CONJUNCTIVAL ABRASION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
CORNEAL ABRASION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
FOOT FRACTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
FOREIGN BODY IN EYE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
INCISIONAL HERNIA	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0012 affected217 at risk
LIGAMENT INJURY	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
MENISCUS LESION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
POST PROCEDURAL HAEMORRHAGE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
STERNAL FRACTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
BLOOD CREATININE INCREASED	Investigations	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
C-REACTIVE PROTEIN INCREASED	Investigations	MedDRA	Systematic Assessment	EG0003 affected214 at risk EG0010 affected217 at risk
WEIGHT DECREASED	Investigations	MedDRA	Systematic Assessment	EG0004 affected214 at risk EG0010 affected217 at risk
DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
GOUT	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ANKYLOSING SPONDYLITIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
ARTHRITIS REACTIVE	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
FLANK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0011 affected217 at risk
FOOT DEFORMITY	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
INTERVERTEBRAL DISC PROTRUSION	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0004 affected214 at risk EG0011 affected217 at risk
MYOSITIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
POLYARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
RHABDOMYOLYSIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
ADENOCARCINOMA PANCREAS	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
BENIGN OVARIAN TUMOUR	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
BREAST CANCER	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
CHOLESTEATOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PANCREATIC CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
PLASMACYTOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
THYROID NEOPLASM	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
UTERINE LEIOMYOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
CEREBRAL ATROPHY	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CEREBRAL HAEMORRHAGE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CEREBROVASCULAR ACCIDENT	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
HEMIPARESIS	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
MIGRAINE	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
MIGRAINE WITH AURA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
NEUROPATHY PERIPHERAL	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
RUPTURED CEREBRAL ANEURYSM	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
SYNCOPE	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0012 affected217 at risk
PREGNANCY	Pregnancy, puerperium and perinatal conditions	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ACUTE PSYCHOSIS	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
DEPRESSED MOOD	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
DEPRESSION	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
PARANOIA	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PSYCHOTIC DISORDER	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
SUICIDE ATTEMPT	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
CALCULUS URETERIC	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
NEPHROTIC SYNDROME	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
RENAL COLIC	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0011 affected217 at risk
RENAL CYST RUPTURED	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
RENAL FAILURE	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
RENAL FAILURE ACUTE	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0005 affected214 at risk EG0011 affected217 at risk
RENAL HAEMORRHAGE	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0003 affected214 at risk EG0012 affected217 at risk
RENAL IMPAIRMENT	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0011 affected217 at risk
BREAST DISCHARGE	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
BREAST FIBROSIS	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
BREAST HYPERPLASIA	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
COLPOCELE	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
DYSMENORRHOEA	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
MENORRHAGIA	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
MENSTRUATION IRREGULAR	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
OVARIAN CYST	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0007 affected214 at risk EG0010 affected217 at risk
PELVIC FLUID COLLECTION	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
POLYCYSTIC OVARIES	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
VAGINAL HAEMORRHAGE	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0011 affected217 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
DYSPNOEA EXERTIONAL	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
LUNG DISORDER	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PAINFUL RESPIRATION	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PLEURISY	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected214 at risk EG0010 affected217 at risk
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ANGIOEDEMA	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0008 affected214 at risk EG0010 affected217 at risk
HYPOAESTHESIA FACIAL	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
ANGIODYSPLASIA	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0012 affected217 at risk
HYPERTENSION	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
HYPERTENSIVE CRISIS	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
HYPOTENSION	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
ILIAC ARTERY STENOSIS	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
INTERMITTENT CLAUDICATION	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
THROMBOSIS	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk
VARICOSE VEIN	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
VASCULITIS	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected214 at risk EG0011 affected217 at risk
VENOUS THROMBOSIS LIMB	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected214 at risk EG0010 affected217 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00035 affected214 at risk EG00111 affected217 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00038 affected214 at risk EG0016 affected217 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG00030 affected214 at risk EG0012 affected217 at risk
ABDOMINAL DISCOMFORT	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00012 affected214 at risk EG0018 affected217 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00024 affected214 at risk EG00113 affected217 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00014 affected214 at risk EG00113 affected217 at risk
APHTHOUS STOMATITIS	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00083 affected214 at risk EG00112 affected217 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00048 affected214 at risk EG00134 affected217 at risk
NAUSEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00020 affected214 at risk EG00112 affected217 at risk
VOMITING	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00011 affected214 at risk EG00114 affected217 at risk
ASTHENIA	General disorders	MedDRA	Systematic Assessment	EG00011 affected214 at risk EG0016 affected217 at risk
FATIGUE	General disorders	MedDRA	Systematic Assessment	EG00020 affected214 at risk EG00119 affected217 at risk
OEDEMA	General disorders	MedDRA	Systematic Assessment	EG00025 affected214 at risk EG00112 affected217 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA	Systematic Assessment	EG00042 affected214 at risk EG00120 affected217 at risk
PYREXIA	General disorders	MedDRA	Systematic Assessment	EG00012 affected214 at risk EG0019 affected217 at risk
BRONCHITIS	Infections and infestations	MedDRA	Systematic Assessment	EG00021 affected214 at risk EG00123 affected217 at risk
GASTROENTERITIS	Infections and infestations	MedDRA	Systematic Assessment	EG00011 affected214 at risk EG0014 affected217 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA	Systematic Assessment	EG00083 affected214 at risk EG00183 affected217 at risk
ORAL HERPES	Infections and infestations	MedDRA	Systematic Assessment	EG00015 affected214 at risk EG0014 affected217 at risk
SINUSITIS	Infections and infestations	MedDRA	Systematic Assessment	EG00014 affected214 at risk EG00113 affected217 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG00022 affected214 at risk EG00119 affected217 at risk
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	MedDRA	Systematic Assessment	EG00032 affected214 at risk EG00115 affected217 at risk
BLOOD CREATININE INCREASED	Investigations	MedDRA	Systematic Assessment	EG00038 affected214 at risk EG00113 affected217 at risk
HYPERCHOLESTEROLAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00046 affected214 at risk EG0018 affected217 at risk
HYPERLIPIDAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00028 affected214 at risk EG0015 affected217 at risk
HYPERTRIGLYCERIDAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00015 affected214 at risk EG0018 affected217 at risk
HYPERURICAEMIA	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0007 affected214 at risk EG00113 affected217 at risk
IRON DEFICIENCY	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG00012 affected214 at risk EG0012 affected217 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00013 affected214 at risk EG0015 affected217 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00015 affected214 at risk EG00117 affected217 at risk
FLANK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00017 affected214 at risk EG00123 affected217 at risk
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00010 affected214 at risk EG00112 affected217 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00014 affected214 at risk EG0013 affected217 at risk
HEADACHE	Nervous system disorders	MedDRA	Systematic Assessment	EG00037 affected214 at risk EG00127 affected217 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA	Systematic Assessment	EG00013 affected214 at risk EG0019 affected217 at risk
PROTEINURIA	Renal and urinary disorders	MedDRA	Systematic Assessment	EG00028 affected214 at risk EG00115 affected217 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00024 affected214 at risk EG00119 affected217 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG00012 affected214 at risk EG0019 affected217 at risk
ACNE	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00030 affected214 at risk EG0016 affected217 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00018 affected214 at risk EG0018 affected217 at risk
HYPERTENSION	Vascular disorders	MedDRA	Systematic Assessment	EG00033 affected214 at risk EG00129 affected217 at risk

ID	Term
D016891	Polycystic Kidney, Autosomal Dominant
D007676	Kidney Failure, Chronic

ID	Term
D007690	Polycystic Kidney Diseases
D052177	Kidney Diseases, Cystic
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D000015	Abnormalities, Multiple
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D000072661	Ciliopathies
D030342	Genetic Diseases, Inborn
D051436	Renal Insufficiency, Chronic
D051437	Renal Insufficiency
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D020123	Sirolimus
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals

ID	Title	Description
BG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
BG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Everolimus	Patients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).			80	214	205	214
EG001	Placebo	Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses			51	217	185	217