Clinical Trials Register

Summary
EudraCT Number:	2011-005216-28
Sponsor's Protocol Code Number:	VNK115640
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:	2012-03-28
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

2011-005216-28

A.3

Full title of the trial

A Multicenter, Randomized, Single-blind, Active-controlled, Parallel Group, Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of a Single Intravenous (6 mg, 12 mg, 18 mg, 24 mg or 36 mg) Dose of the Neurokinin-1 Receptor Antagonist, Vestipitant (GW597599), Compared with a Single 4 mg Intravenous Ondansetron Hydrochloride Dose for the Treatment of Breakthrough Post-Operative Nausea and Vomiting after Failed Prophylaxis with an Ondansetron-Containing Regimen in Patients Undergoing Non-Emergency Surgical Procedures

A.3.1

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

A research study to test the safety, tolerability and how well vestipitant works when compared to ondansetron in treating nausea and vomiting in patients following non-emergency surgeries when preventative treatment with ondansetron has failed

A.4.1

Sponsor's protocol code number

VNK115640

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline
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	GlaxoSmithKline
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	GlaxoSmithKline
B.5.2	Functional name of contact point	Vice President, Discovery Medicine
B.5.3	Address:
B.5.3.1	Street Address	709 Swedeland Road, UW2230
B.5.3.2	Town/ city	King of Prussia
B.5.3.3	Post code	PA 19406-2711
B.5.3.4	Country	United States
B.5.4	Telephone number	+1610270 4800
B.5.5	Fax number	+1610270 7777
B.5.6	E-mail	richard.a.brigandi@gsk.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	Vestipitant
D.3.2	Product code	GW597599
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	VESTIPITANT
D.3.9.1	CAS number	334476-46-9
D.3.9.2	Current sponsor code	GW597599
D.3.9.4	EV Substance Code	SUB29227
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.IMP: 2
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 2mg/ml
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	Odansetron hydrochloride
D.3.4	Pharmaceutical form	Solution for infusion
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.3.9.1	CAS number	103639-04-9
D.3.9.3	Other descriptive name	Ondansetron Hydrochloride Dihydrate
D.3.9.4	EV Substance Code	SUB03517MIG
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

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 (PONV)

E.1.1.1

Medical condition in easily understood language

Nausea and sickness after an operation

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	10036285
E.1.2	Term	Postoperative nausea
E.1.2	System Organ Class	100000004863

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 efficacy, safety, and tolerability of 6 mg, 12 mg, 18 mg, 24 mg, or 36 mg IV doses of vestipitant versus a standard dose of 4 mg ondansetron to treat breakthrough PONV after a failed prophylaxis regimen that includes 4 mg IV ondansetron prior to surgery. To examine the benefit of IV doses of vestipitant on post-operative symptoms of nausea compared to ondansetron.
• To evaluate the impact of IV doses of vestipitant on discharge readiness and time to discharge compared to ondansetron.
• To evaluate the PK and exposure-response relationship of IV vestipitant in subjects with PONV.

E.2.2

Secondary objectives of the trial

None

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or Female post-operative surgical subjects between the ages of 18-75 years of age, inclusive, at the time of signing the informed consent.
2. A female subject is eligible to participate if she is
• of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea
or
• of child-bearing potential and agrees to use one of the contraception methods listed in the protocol for an appropriate period of time (as determined by the product label or Investigator) prior to Study Treatment dosing, to sufficiently minimize the risk of pregnancy at that point.
3. Has 3 or more of the following independent risk factors for PONV:
a. female gender
b. non-smoker (defined for this study as one who has not smoked or used tobacco [including chewing tobacco, a nicotine patch, or other nicotine-withdrawal formulation] for at least the previous 6 months. Rare/infrequent [2 or less cigarettes a week] smoking is allowed, at the Investigator’s discretion)
c. history of PONV or motion sickness
d. planned post-operative opioids.
4. Has received one dose of ondansetron as part of a PONV prophylaxis regimen for the surgical procedure.
5. Has received general anesthesia with an anesthetic regimen as described in the Anesthetic Regimen Guidelines.
6. Meets American Society of Anesthesiologists (ASA) Physical Status Classification of 1 or 2 without an “E” modifier preoperatively on the day of surgery and has hematology and blood chemistry values within acceptable limits for surgery.
7. Is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.
8. Experiences breakthrough PONV defined as:
a. post-operative nausea of ≥ 7 on the Nausea Numeric Rating Scale with 0 being no nausea and 10 being the worst nausea possible
-OR-
b. nausea resulting in a subject request for an anti-emetic
-OR-
c. an episode of emesis or retching

E.4

Principal exclusion criteria

1. A history of HIV.
2. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Screening.
3. An ALT or AST >2.5 x ULN at Screening.
4. Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing.
5. Lactating females.
6. The subject is scheduled to undergo a laparoscopic biopsy only
7. The subject has a history of or is scheduled to undergo cardiac/cardiothoracic surgery
8. The subject is scheduled to receive neuroaxial anesthesia (e.g., epidural, spinal, or caudal anesthesia) or total IV anesthesia.
9. The subject is scheduled to receive propofol for maintenance of anesthesia (propofol as an induction agent is allowed).
10. The subject is scheduled to receive an NK1 inhibitor (aprepitant/fosaprepitant) as part of a PONV prophylaxis regimen for the surgical procedure.
11. The subject is scheduled to have gastric contents suctioned continuously during the surgical procedure via a nasogastric tube, or a nasogastric or oral gastric tube during the post-operative period. A single pass at the beginning or at the end of the surgical procedure, and intraoperative gastric suctioning of air, will be permitted.
12. The subject received an investigational drug within 30 days or was scheduled to receive any investigational drug in addition to vestipitant during the study period.
13. The subject has persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to, gastric outlet obstruction, hypercalcemia, active peptic ulcer, increased intracranial pressure, chemotherapy, or brain metastases.
14. The subject received radiation therapy to the abdomen or the pelvis within 7 days prior to receiving study medications and/or received radiation therapy to the abdomen or the pelvis in the evaluation period.
15. The subject has a history of wound dehiscence.
16. The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
17. QTc prior to Study Treatment as follows:
Pre-Operative or Post Operative, Pre-Dose QTc > 450 msec ( >480 msec
for subject with Bundle Branch Block).
18. The subject has any current or past medical condition (e.g., vagotomy) and/or required medication to treat a condition that could affect the evaluation of the study.
19. The subject has a known contraindication or hypersensitivity to ondansetron or ondansetron injection, any scheduled anaesthetic or analgesic agents, vestipitant or any component of the vestipitant formulation including Captisol™.
20. The subject received medication with known or potential antiemetic activity after the induction of anaesthesia (during the intraoperative or post-operative period) other than the planned Study Treatment, ondansetron or vestipitant.
21. Current or planned use of strong or moderate inhibitors of CYP3A within 7 days or inducers of CYP3A within 14 days prior to study medication administration.
22. The subject is unwilling or unable to follow the procedures outlined in the protocol.
23. The subject is mentally or legally incapacitated.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is number of patients achieving Complete Response after receiving study drug to treat breakthrough PONV.

The primary safety and tolerability endpoints will be adverse and serious adverse event observation and safety laboratory evaluations.

Additional efficacy evaluation will include a numeric Nausea Numeric Rating Scale (NNRS) for assessment of subject nausea.

Time to PONV Discharge-Ready.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary efficacy endpoint is number of subjects achieving Complete Response after receiving Study Treatment to treat breakthrough PONV. The period for the primary efficacy endpoint begins 10 minutes after infusion end. Complete Response is defined as no emesis and no further rescue medication from 10 minutes after infusion end through 24 hours or discharge from the hospital/clinic, whichever is sooner.

E.5.2

Secondary end point(s)

None

E.5.2.1

Timepoint(s) of evaluation of this end point

None

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

Yes

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

E.6.12

Pharmacoeconomic

Yes

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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.8.2.4

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

Yes

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

Germany

Poland

Russian Federation

Ukraine

United Kingdom

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.8.9.1

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

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:

133

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

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

200

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)

Normal standard of care

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

2012-05-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-23

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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