Clinical Trials Register

Summary
EudraCT Number:	2012-000299-40
Sponsor's Protocol Code Number:	CRAD001C2121
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2016-05-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2012-000299-40

A.3

Full title of the trial

A randomized, open label, two-way crossover study investigating the relative bioavailability of a single 5 mg dose of everolimus administered as either 5x1 mg everolimus intact tablets or 5x1 mg everolimus tablets suspended in 30 mL of water to healthy subjects

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

CRAD001C2121

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/105/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma Services AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+4161324 1111
B.5.5	Fax number	+4161324 8001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Everolimus
D.3.2	Product code	RAD001
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy volunteers

E.1.1.1

Medical condition in easily understood language

Not applicable

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the bioavailability of:
5 x 1 mg everolimus intact tables, and
5 x 1 mg everolimus tablets suspended in 30 mL of water

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of the 1 mg everolimus tablets administered as suspension and as intact tablets

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Female or male healthy subjects from 18 to 55 years of age;
• Female subjects must be postmenopausal (no menstrual bleeding for 12 months), or surgically sterilized at least 6 months prior to screening;
• Good health status as determined by past medical history, physical examination, vital signs, electrocardiogram and laboratory tests within normal ranges at screening;
• Vital signs (after 3 minutes resting measured in the supine position) must be within the ranges specified in the protocol

E.4

Principal exclusion criteria

• Smokers defined as having used tobacco products in the previous 3 months or having urine cotinine levels greater than 500 ng/mL tested at screening and each baseline visit;
• Use of any prescription medication within 1 month prior to dosing or any over-the-counter (OTC) medication within 2 weeks prior to dosing;
• Consumption of grapefruit products within 1 week prior to dosing;
• Participation in any clinical investigation within 4 weeks prior to dosing;
• Donation or loss of 450 mL or more of blood within 56 days prior to dosing;
• Women who are of child-bearing potential, or pregnant, or breast feeding (positive serum pregnancy test for β-hCG at screening and each baseline visit);
• A known hypersensitivity to rapamycins and their derivates or drugs similar to RAD001, e.g. macrolides;
• Any subject who has been diagnosed with type I or II diabetes, hyperglycemia or impaired glucose intolerance;
• History of any significant respiratory system chronic brochospastic disease (including asthma and COPD, treated or not treated).
• History of atopic allergy (asthma, urticaria, eczematous dermatitis);
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study.
• History of immunosuppression, including a known positive HIV test result;
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result;
• Evidence of alcohol and drug usage as indicated by laboratory assays performed at screening and prior to baseline period.

E.5 End points

E.5.1

Primary end point(s)

Primary pharmacokinetic parameters: AUC(0-t), AUC(0-inf) and Cmax

E.5.1.1

Timepoint(s) of evaluation of this end point

Full pharmacokinetic whole blood samples will be drawn at each of the two treatment periods as follows: 1 pre-dose sample < 15min prior to administration of study drug and 17 postdose
samples at 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h and 144 h after administration of study drug.

E.5.2

Secondary end point(s)

- Secondary pharmacokinetic parameters: Tmax, λz, Vd/F, CL/F and t1/2
- Safety endpoints (evaluation of adverse events and serious adverse events, vital signs, ECG, laboratory results (hematology, blood chemistry, urinalysis)

E.5.2.1

Timepoint(s) of evaluation of this end point

- Full pharmacokinetic whole blood samples will be drawn at each of the two treatment periods as follows: 1 pre-dose sample < 15min prior to administration of study drug and 17 postdose
samples at 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h and 144 h after administration of study drug.
- Safety laboratory assessments will be performed regularly. Hematology and biochemistry laboratory parameters will be evaluated at screening, each of the 2 baseline visits, 144 hours post-dose and at the study completion visit.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Bioavailability

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

test formulation

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

Yes

E.8.4

Will this trial be conducted at multiple sites globally?

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Not applicable

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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