Clinical Trials Register

Summary
EudraCT Number:	2006-005515-10
Sponsor's Protocol Code Number:	0869-134
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-08-20
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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2006-005515-10

A.3

Full title of the trial

A Multi-center, Open-label, 5-Part Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Aprepitant and Fosaprepitant Dimeglumine in Pediatric Patients Receiving Emetogenic
Chemotherapy

A.3.1

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

Prevention Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients

A.3.2

Name or abbreviated title of the trial where available

Prevention Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients

A.4.1

Sponsor's protocol code number

0869-134

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00818259

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/168/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Global Clinical Trials Operations
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive P.O. Box 100
B.5.3.2	Town/ city	Whitehouse Station
B.5.3.3	Post code	08889-0100
B.5.3.4	Country	United States
B.5.4	Telephone number	1908740-2318
B.5.5	Fax number	1215661-6459
B.5.6	E-mail	denesh_chitkara@merck.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	Aprepitant
D.3.2	Product code	MK-0869
D.3.4	Pharmaceutical form	Powder for oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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	APREPITANT
D.3.9.1	CAS number	170729-80-3
D.3.9.2	Current sponsor code	MK-0869
D.3.9.4	EV Substance Code	SUB20017
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	125
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.IMP: 2
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	Yes
D.2.1.1.1	Trade name	IVEMEND
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Fosprepitant
D.3.2	Product code	MK-0517
D.3.4	Pharmaceutical form	Lyophilisate for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FOSAPREPITANT
D.3.9.1	CAS number	265121-04-8
D.3.9.2	Current sponsor code	MK-0517
D.3.9.4	EV Substance Code	SUB20017
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	150
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

Chemotherapy Induced Nausea and Vomiting (CINV)

E.1.1.1

Medical condition in easily understood language

prevention of chemotherapy induced nausea and vomiting

E.1.1.2

Therapeutic area

Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10036899
E.1.2	Term	Prophylaxis against chemotherapy induced vomiting
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10056989
E.1.2	Term	Nausea post chemotherapy
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

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 estimate aprepitant plasma concentration profiles and pharmacokinetic parameters (e.g. AUC0-∞, AUC0-24, Cmax, Tmax, CL/F, t1/2 and C24 hr, as appropriate) obtained in patients birth to < 6 months, 6 months to < 2 years, 2 to < 6 years, and 6 to < 12 years, receiving moderately or highly emetogenic chemotherapy or a chemotherapy regimen not previously tolerated due to nausea and/or vomiting administered a single dose or 3 day regimen of oral aprepitant.
Refer to protocol for additional main objectives

E.2.2

Secondary objectives of the trial

To estimate intravenous dexamethasone plasma concentration profiles and pharmacokinetic parameters (e.g. AUC0-24, Cmax, Tmax, t1/2, CL/F, and C24 hr) obtained in patients birth to 12 months of age, receiving moderately or highly emetogenic chemotherapy or a chemotherapy regimen not previously tolerated due to nausea and/or vomiting administered standard (ondansetron) therapy, and 3 day oral aprepitant.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is 0 (at least 37 weeks gestation) to 17 years of age on the day they are allocated into the study.
2. Patient is scheduled to receive moderately or highly emetogenic chemotherapy for a documented malignancy OR patient did not tolerate a previously administered chemotherapy regimen, for a documented malignancy, secondary to nausea and/or vomiting that is planned to be repeated.
3. Patient is expected to receive ondansetron as part of their antiemetic regimen.
4. Female patient who has begun menses has a negative urine pregnancy test prior to randomization. Females of reproductive potential who have previously been sexually active must agree to use a double-barrier form of contraception for at least 14 days prior to, throughout, and for at least 1 month following the last dose of study medication. Women taking oral contraception agents must agree to add double barrier form of contraception. Abstinence is also considered an acceptable form of contraception, however, for countries where abstinence is not considered an acceptable form of contraception, two acceptable birth control methods must be used for females of reproductive potential who have previously been sexually active.
5. Patients weight:
< 6 months ≥ 3.0 kg
> 6 months ≥ 6.0 kg
> 2 years ≥ 7.6 kg
6. Patient has a preexisting functioning venous catheter prior to receiving aprepitant/fosaprepitant designated for pharmacokinetic sampling.

E.4

Principal exclusion criteria

1. Patient is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy.
2. Patient has ever participated in a study with aprepitant or fosaprepitant, is currently participating in a study with casopitant or has taken a non-approved (investigational) drug within the last 4 weeks. Note: Patients on investigational studies with marketed chemotherapeutic agents (whether marketed explicitly for children or only marketed for adults and usually applied for children as well, with appropriate dosage adjustments) are allowed to enroll if they fulfill all other entry criteria.
3. Patient is allergic to aprepitant, fosaprepitant, ondansetron or any other 5 HT3 antagonist.
4. Patient has a symptomatic primary or metastatic CNS malignancy. Patients who are asymptomatic are allowed to participate.
5. Patients must satisfy all laboratory value criteria as stated in the protocol.
6. Patient has been treated with specified antiemetic agents within 48 hours of study Day 1.
7. Patient has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of their chemotherapy regimen.
Exceptions:
 Patients who are receiving chronic (>72 hours), daily steroid therapy can be enrolled provided the steroid dose is not >0.14 mg/kg up to 10 mg of prednisone daily or equivalent.
 Patients are allowed to receive a single dose of a corticosteroid within 3 days prior (but not on the day of study drug administration) provided it is < the equivalent of 20 mg of prednisone.
 Patients are allowed to receive corticosteroids administered for antiemetic prophylaxis starting on study Day 1.
8. Patient is taking or has taken within 7 days of study Day1 CYP3A4 substrates or inhibitors (moderate to strong) as stated in protocol.
9. Patient is taking or has taken within 30 days of study Day1 CYP3A4 inducers as stated in protocol.
10. Patient is currently taking warfarin.
11. Patient has a known history of QT prolongation.

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetic Endpoint: aprepitant plasma pharmacokinetic (PK) profile (AUC0-24, Cmax, Tmax, and C24hr) of the administered dose of aprepitant or fosaprepitant on Day 1 in pediatric patients birth to 17 years will be determined. In Part IA and IV aprepitant plasma PK will be assessed 24hr post administration of aprepitant on Days 2 and 3.

Safety Endpoint: drug related, serious, and serious drug-related adverse experience(s) during aprepitant and/or fosaprepitant therapy plus 14 days post therapy or drug-related adverse experiences(s) leading to discontinuation of aprepitant/fosaprepitant therapy.

E.5.1.1

Timepoint(s) of evaluation of this end point

0 to 72 hours post study drug dose

E.5.2

Secondary end point(s)

The PK of intravenous dexamethasone, given with (Part IV) and without (Part III) aprepitant will be determined in patients birth to 1 year.

E.5.2.1

Timepoint(s) of evaluation of this end point

0 to 24 hours post dexamethasone dose

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

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

E.7.1.3.1

Other trial type description

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

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

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Canada

Colombia

Ecuador

Mexico

Peru

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

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

Yes

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minors from birth up to 17 years of age

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

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)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-09-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-01-20

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