Clinical Trials Register

Summary
EudraCT Number:	2011-006006-27
Sponsor's Protocol Code Number:	0869-219
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-14
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-006006-27

A.3

Full title of the trial

A Phase IIb, Partially-Blinded, Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Aprepitant in Pediatric Patients for the Prevention of Post Operative Nausea and Vomiting

IIb fázisú, részben vakosított, randomizált, aktív összehasonlító készítménnyel kontrollált klinikai vizsgálat az aprepitant farmakokinetikájának, farmakodinamikájának, biztonságosságának és tolerálhatóságának az értékelésére műtét utáni hányinger és hányás megelőzésében gyermekeknél.

A.3.1

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

Pediatric study to evaluate the appropriate dose for aprepitant in pediatric patients undergoing surgery.

Klinikai vizsgálat az aprepitant megfelelő adagjának az értékelésére műtéten átesett gyermekeknél.

A.3.2

Name or abbreviated title of the trial where available

Pediatric PONV PK/PD Study

Klinikai vizsgálat az aprepitant megfelelő adagjának az értékelésére műtéten átesett gyermekeknél.

A.4.1

Sponsor's protocol code number

0869-219

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

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 PO 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	+1267305-7215
B.5.5	Fax number	+1267305-6441
B.5.6	E-mail	susan_loftus@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.3.9.3	Other descriptive name	aprepitant
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	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.3.9.3	Other descriptive name	aprepitant
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	40
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Zofran Injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Operations UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Zofran Injection
D.3.2	Product code	Ondasetron Hydrochloride
D.3.4	Pharmaceutical form	Solution 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	ondansetron
D.3.9.3	Other descriptive name	ondansetron
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Post Operative Nausea and Vomiting in surgical patients

Műtét utáni hányinger és hányás műtéten átesett betegeknél.

E.1.1.1

Medical condition in easily understood language

Prevention of postoperative nausea vomiting

Műtét utáni hányinger és hányás megelőzése.

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	10036901
E.1.2	Term	Prophylaxis against postoperative nausea and vomiting
E.1.2	System Organ Class	100000004865

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 post-operative aprepitant plasma concentration profiles and pharmacokinetic parameters by population analysis including historical data (e.g. Cmax, Tmax, AUC0-∞, t1/2, CL/F) in Dose 1, 2, 3 (Dose 4 if needed) obtained from pediatric patients from birth to 17 years of age administered oral aprepitant preoperatively.

Safety:
To evaluate the safety and tolerability of the administered dose(s) of aprepitant in pediatric patients from birth to 17 years of age.

A műtét utáni aprepitant plazma koncentráció profiljának és farmakokinetikai paramétereinek populáció analízissel történő meghatározása, beleértve a múltbeli adatok felhasználását (pl. Cmax, Tmax, AUCO-∞, t1/2, CL/F), 1-es, 2-es és 3-as adagban (4-es adag, ha szükséges) olyan 18 évesnél fiatalabb betegeknél, akik a műtétet megelőzően szájon keresztül aprepitantot kapnak.

Biztonságosság:
Az aprepitant alkalmazott adagjainak a biztonságosságának és tolerálhatóságának az értékelése 18 évesnél fiatalabb betegeknél.

E.2.2

Secondary objectives of the trial

No secondary objective

Nincs másodlagos célkitűzés.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is birth (at least 37 weeks gestation and ≥3 kg of weight) to 17 years of age at the time of randomization.
2. Patient is scheduled to receive general anesthesia AND:
Patients must have at least one of the following risk factors for PONV (in addition to receiving general anesthesia):
o Surgery with an associated risk of PONV: tonsillectomy, adenoidectomy, strabismus surgery, dental surgery, hydrocelectomy, orchidopexy or herniorraphy –OR-
o Operative procedure associated with PONV: intraoperative use or anticipated opioid administration within the first 24 following surgery.

1. A beteg életkora a vizsgálatba való beválasztás (randomizáció) napján 0 (legalább 37 gesztációs hét) és 18 év között van és testsúlya megegyezik vagy meghaladja a 3 kg-ot.
2. A betegnél általános érzéstelenítés alkalmazását tervezik ÉS:
A betegnél a műtét utáni hányinger és hányás (PONV) alábbi rizikófaktorai közül legalább 1 jelenléte szükséges (az általános érzéstelenítés alkalmazásán kívül):
•A PONV kockázatával járó műtét: garat- és orrmandulaműtét, kancsalság műtése, fogászati műtét, herevízsérv műtét, here leszállító műtét vagy sérvplasztika – VAGY –
•A PONV-val összefüggő beavatkozás: opioid alkalmazása a műtét alatt vagy opioid alkalmazását tervezik a műtétet követő 24 órán belül.

E.4

Principal exclusion criteria

1. Patient is undergoing emergency surgery for a life threatening condition.
2. Patient is scheduled to receive propofol for maintenance of anesthesia. (Note: propofol is permitted for induction of anesthesia).
3. Patient is expected to receive opioid antagonists (e.g., naloxone, naltrexone) or benzodiazepine antagonists (e.g., flumazenil)
4. Patient is scheduled to undergo cardiac or neurosurgery.
5. Patient has vomited within 24 hours prior to surgery.
6. Patient has an active infection (e.g., pneumonia), any uncontrolled disease (e.g., diabetic ketoacidosis, pre-existing gastrointestinal conditions/gastrointestinal obstruction) except for malignancy, or a history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study drug/comparator to the patient.
7. Patient has a nasogastric or oral gastric tube intra- or post-operatively for suctioning gastric contents (Note: nasogastric or oral gastric tube intra- or post-operatively may ONLY be used for feeding. Patients should be excluded if a nasogastric or oral gastric tube is routinely used for the type of surgery to be performed).
8. Patients with a know history of QT prolongation.
9. Patient is allergic to aprepitant, ondansetron or any 5-HT3 antagonist.
10. Patient is taking the anti-coagulant warfarin.

1. A beteg sürgősségi műtéten esik át életveszélyes állapota miatt.
2. A betegnél propofol alkalmazását tervezik az érzéstelenítés fenntartására. (Megjegyzés: a propofol engedélyezett az érzéstelenítés beindítására.)
3. A beteg várhatóan opioid antagonista szereket (pl. naloxon, naltrexon) vagy benzodiazepin antagonista szereket (pl. flumazenil) fog kapni.
4. A betegnél szív- vagy idegsebészeti műtétet terveznek.
5. A betegnél hányás jelentkezett a műtétet megelőző 24 órán belül.
6. A betegnek aktív fertőzése (pl. tüdőgyulladás), vagy valamilyen nem megfelelően kezelt betegsége van (pl. diabéteszes ketoacidózis, fennálló emésztőrendszeri zavar/elzáródás) a rosszindulatú daganatok kivételével, vagy a beteg kórtörténetében olyan betegség szerepel, amely a vizsgáló orvos véleménye szerint befolyásolhatja a vizsgálat eredményét, vagy indokolatlan kockázatnak teszi ki a beteget a vizsgálati/összehasonlító készítmény alkalmazása során.
7. A betegnek gyomorszondát vezetnek le orron vagy szájon keresztül a gyomortartalom kiszívására műtét alatt vagy után. (Megjegyzés: az orron vagy szájon keresztül levezetett gyomorszondát a műtét alatt vagy után CSAK táplálásra szabad használni. Nem választhatók be a vizsgálatba azok a betegek, akiknél az orron vagy szájon keresztül levezetett gyomorszondát az adott típusú elvégzendő műtéthez rutinszerűen használják.)
8. A beteg kórtörténetében QT megnyúlás szerepel.
9. A beteg allergiás az aprepitantra, az ondánszetronra vagy bármely 5-HT3 antagonista szerre.
10. A beteg véralvadásgátló warfarint szed.

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetic endpoints are Cmax, Tmax, AUC0-∞, t1/2 and CL/F estimated by population methods, including the use of historic data in the population modeling, in each age group
for all aprepitant treatments.

Farmakokinetikai végpontok: a populációs módszerek által megbecsült Cmax, Tmax, AUC0→∞, t1/2 és CL/F értékek beleértve a múltbeli adatok felhasználását a populáció modellezésében az aprepitant kezelési csoportok minden egyes korcsoportjában.

E.5.1.1

Timepoint(s) of evaluation of this end point

-30 to 60 minutes prior to aprepitant administration
-2 to 4 hours post aprepitant administration
-5 to 7 hours post aprepitant administration
-8 to 10 hours post aprepitant administration.

Az aprepitant alkalmazását megelőző 30-60 perccel
Az aprepitant alkalmazását követő 2-4 órával
Az aprepitant alkalmazását követő 5-7 órával
Az aprepitant alkalmazását követő 8-10 órával

E.5.2

Secondary end point(s)

There are no secondary end points for this study.

Ebben a vizsgálatban nincsenek másodlagos végpontok.

E.5.2.1

Timepoint(s) of evaluation of this end point

There are no secondary end points for this study.

Ebben a vizsgálatban nincsenek másodlagos végpontok.

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

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)

Yes

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

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

Yes

E.8.1.7.1

Other trial design description

Részben vakosított

Partial Blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

Chile

Czech Republic

Guatemala

Hungary

India

Italy

Mexico

Peru

Puerto Rico

Russian Federation

Spain

Turkey

Ukraine

United States

E.8.7

Trial has a data monitoring committee

Yes

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

Utolsó beteg utolsó vizitje

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

Number of subjects for this age range:

260

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:

130

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

Yes

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

Yes

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

Pediatric patients birth to 17 years of age

18 évesnél fiatalabb betegek

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

230

F.4.2.2

In the whole clinical trial

260

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

Nincs ilyen.

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

2012-11-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-26

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Clinical trials