Clinical Trials Register

Summary
EudraCT Number:	2005-005003-41
Sponsor's Protocol Code Number:	392MD/15/C
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2006-02-01
Trial 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2005-005003-41

A.3

Full title of the trial

A randomised, active control, double-blind, double-dummy, parallel-group, multi-national study to assess the efficacy, tolerability and safety of the granisetron transdermal delivery system (GTDS) in chemotherapy-induced nausea and vomiting (CINV) associated with the administration of moderately or highly emetogenic multi-day chemotherapy.

A.4.1

Sponsor's protocol code number

392MD/15/C

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Strakan Pharmaceuticals Ltd
B.1.3.4	Country	United Kingdom
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Information not present in EudraCT
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	Granisetron transdermal delivery system
D.3.2	Product code	GTDS
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Granisetron
D.3.9.1	CAS number	109889-09-0
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	34.3
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Information not present in EudraCT
D.2.1.1.1	Trade name	Kytril
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products 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.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Granisetron hydrochloride
D.3.9.1	CAS number	107007-99-8
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	2 (two 1mg to tablets /capsule)
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Transdermal patch
D.8.4	Route of administration of the placebo	Transdermal use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule*
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

Chemotherapy-induced nausea and vomiting (CINV) associated with the administration of moderately or highly emetogenic multi-day chemotherapy.

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 demonstrate non-inferiority of the GTDS efficacy compared with oral granisetron efficacy with regard to complete control of CINV from the first administration until 24 h after the last administration of the moderately/highly emetogenic multi-day chemotherapy

E.2.2

Secondary objectives of the trial

Complete Control of CINV from 1st administration of chemotherapy until patch removal and during successive 24h intervals from 1st administration of chemotherapy until patch removal and time to treatment failure. Time to first emetic episode and number of emetic episodes. Complete Response of CINV from 1st administration until last administration of chemotherapy and from 1st administration chemotherapy until patch removal and during successive 24h intervals from 1st administration of chemotherapy until patch removal. Severity of nausea and frequency of more than mild nausea. Severity of vomiting. Rescue Medication: time to 1st administration. Patient’s satisfaction of treatment. To compare GTDS with oral granisetron with respect to safety: AEs (local tolerance issues at site of patch application will be recorded as AEs). Changes from Screening to end of treatment for vital signs, ECG, physical examination and laboratory values. To assess adhesion of GTDS over 7 day application period.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

Male or female aged ≥18yrs (no upper limit)
Woman not of childbearing potential, i.e:
• A surgically sterilised (tubal ligation and/or hysterectomy) female patient
• A post-menopausal female patient (amenorrhoea for at least one year prior to Screening Visit)
Woman of childbearing potential, i.e:
• A female patient using a highly effective method of birth control (e.g., intrauterine contraceptive device; combined oral contraceptives; contraceptive implant; contraceptive skin patch or cervical ring) for 30 days prior to the start of the study, and agree to continue such precautions for one month after study completion.
• A female patient with a surgically sterilised male partner (vasectomy)

Female patients must have a negative pregnancy test at the Screening Visit.
Histologically and/or cytologically confirmed cancer with Eastern Cooperative Oncology Group (ECOG) ≤2
Life expectancy of ≥3 months
Assigned to receive the first cycle of a new multi-day chemotherapy regimen including the daily administration of cytotoxic agent(s) with the emetogenic potential of level 3-5 (Hesketh Classification) on 3-5 days
Patients able to read and write at a competent level to understand the study procedures and capable of giving legal consent.
Patients having provided written informed consent
The study will aim to select countries and centres to ensure that a representative patient population with regard to ethnic and racial background will be included in the study.

E.4

Principal exclusion criteria

The presence of any of the following criteria constitutes a cause for the exclusion of the patient from the study:
Previous History
• Hypersensitivity to adhesive plasters
• Contraindications to 5-HT3 receptor antagonists
• Patients who have already been included in a clinical study with the GTDS
• Any other relevant medical history at the discretion of the Investigator
Concomitant Medical Condition
• Current alcohol, drug or medication abuse
• Breast feeding women
• Clinically relevant abnormal laboratory values at the discretion of the Investigator
• Clinically relevant hepatic, renal, infectious, neurological or psychiatric disorders or any other major systemic illness at the discretion of the Investigator
• Any cause for nausea and vomiting other than CINV
• Any episode of retching, vomiting or uncontrolled nausea within 72 h prior to the administration of the chemotherapy
• Clinically relevant ECG parameters at the discretion of the Investigator and/or QTc > 450ms for male patients and QTc > 470ms for female patients
• Mental conditions rendering the patient unable to understand the nature, scope and possible consequences of the study
Concomitant Therapy/Medication
• Concomitant radiotherapy of total body, brain or upper abdomen within one week of study entry or planned during the study
• A patient taking a medication to control the symptoms of a brain tumour, brain metastasis or seizure disorder
• Patients using SSRI antidepressants (unless they are on a stable dose for the duration of the study)
• Receipt of any other investigational drug <30 days before the study or during the study
• Scheduled to receive a NK1 receptor antagonists, dopamine receptor antagonist or another 5-HT3 receptor antagonist between 72 h prior to the administration of the chemotherapy and patch removal (Visit 6)
• Drugs known to increase the QTc interval.
Other
• Patients unlikely to comply with the study protocol, e.g. uncooperative attitude, inability to return for follow-up visits and unlikelihood of completing the study
In addition to these exclusion criteria, patients will be withdrawn from the study if the patch is more than 50% detached from the patient’s skin at Visit 1.
At Visit 1, prior to the administration of the capsule, concomitant medication, AEs and adhesion of patch should be checked. If there are violations of eligibility criteria the patient should be withdrawn from the study, the patch is to be removed and the patient is to be offered the site’s standard of anti emetic care.
If the patient’s chemotherapy is cancelled or delayed by more than one day, therefore the patch will have been applied more than 48 h before chemotherapy, the patient should be withdrawn from the study, the patch is to be removed and the patient is to be offered the site’s standard of anti emetic care.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is:
• % of patients achieving Complete Control of CINV (CC, i.e. no vomiting and/or retching, no more than mild nausea and no rescue medication) from the first administration until 24 h after the last administration of the cytotoxic agent(s) with the moderately or highly emetogenic potential (according to Hesketh Classification)

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

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Double dummy

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.8.3

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.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

Last patient last visit

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 months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-02-01.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	24
F.4.2	For a multinational trial
F.4.2.1	In the EEA	168
F.4.2.2	In the whole clinical trial	576

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

2006-03-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials