Clinical Trials Register

Summary
EudraCT Number:	2014-003595-23
Sponsor's Protocol Code Number:	CIP-DEX/001/14
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:	2014-10-27
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

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2014-003595-23

A.3

Full title of the trial

A double-blinded, parallel-group, randomized, single dose study to assess the pharmacokinetic bioequivalence of ciprofloxacin (0.3%) and dexamethasone (0.1%) otic suspension (Indoco for Actavis) versus Ciprodex® otic suspension (Alcon) in Pediatric Subjects with intact tympanostomy tubes.

Podwójnie zaślepione, prowadzone w grupach równoległych badanie z randomizacją, mające na celu ocenę biorównoważności farmakokinetycznej pojedynczej dawki zawiesiny do uszu (cyprofloksacyna 0,3% i deksametazon 0,1%, Indoco dla Actavis) względem zawiesiny do uszu Ciprodex® (Alcon) u dzieci z drożnym drenażem ucha środkowego.

A.3.1

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

Study assessing pharmacokinetic bioequivalence of ciprofloxacin (0.3%) and dexamethasone (0.1%) otic suspension (Indoco for Actavis) versus Ciprodex® otic suspension (Alcon) in Pediatric Subjects with intact tympanostomy tubes.

Badanie Kliniczne oceniające biorównoważność farmakokinetyczną pojedynczej dawki zawiesiny do uszu (cyprofloksacyna 0,3% i deksametazon 0,1%, Indoco dla Actavis) względem zawiesiny do uszu Ciprodex® (Alcon) u dzieci z drożnym drenażem ucha środkowego.

A.4.1

Sponsor's protocol code number

CIP-DEX/001/14

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	Watson Laboratories 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	Watson Laboratories 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	Watson Laboratories Inc.
B.5.2	Functional name of contact point	Clinical R&D Department
B.5.3	Address:
B.5.3.1	Street Address	Morris Corporate Center III, 400 Interpace Parkway Parsippany
B.5.3.2	Town/ city	New Jersey
B.5.3.3	Post code	07054
B.5.3.4	Country	United States
B.5.4	Telephone number	+18622617471
B.5.5	Fax number	+18622617935
B.5.6	E-mail	Nageshwar.Thudi@actavis.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	Ciprofloxacin (0.3%) and Dexamethasone (0.1%) otic suspension
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Ear drops, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Auricular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ciprofloxacin Hydrochloride
D.3.9.1	CAS number	86393-32-0
D.3.9.4	EV Substance Code	SUB01316MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXAMETHASONE
D.3.9.1	CAS number	50-02-2
D.3.9.4	EV Substance Code	SUB07017MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
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.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	CIPRODEX®
D.2.1.1.2	Name of the Marketing Authorisation holder	Alcon, Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Ear drops, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Auricular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ciprofloxacin Hydrochloride
D.3.9.1	CAS number	86393-32-0
D.3.9.4	EV Substance Code	SUB01316MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXAMETHASONE
D.3.9.1	CAS number	50-02-2
D.3.9.4	EV Substance Code	SUB07017MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
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

Patients with current or previous history of acute otitis media (AOM) and recurrent acute otitis media (RAOM).

E.1.1.1

Medical condition in easily understood language

Patients who suffer from acute ear inflammatory (Acute otitis media (AOM) and recurrent acute otitis media (RAOM).

E.1.1.2

Therapeutic area

Diseases [C] - Ear, nose and throat diseases [C09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10033079
E.1.2	Term	Otitis media acute
E.1.2	System Organ Class	10021881 - Infections and infestations

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 facilitate market entry this study will compare the pharmacokinetics of topically applied product - generic Ciprofloxacin (0.3%) and Dexamethasone (0.1%) to the United States marketed Ciprodex® (ciprofloxacin 0.3% and dexamethasone 0.1%) Sterile Otic Suspension in dose 4 drops in children (aged 5-12 years) with patent, intact tympanostomy tubes.

E.2.2

Secondary objectives of the trial

Study is designed to determine pharmacokinetic, safety and tolerability bioequivalence of a topically applied product.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Pediatric male or female patients aged between 5 to 12 years, inclusive, at the first time of signing of the informed consent by their parents/legal representatives.
2. Completed the screening process within 30 days prior to Baseline dosing.
3. Body mass index (BMI) between 5th and 95th percentile for age (see Appendix 2 and 3 for boys and girls, respectively).
4. Subject’s parents/legal representative has understood and signed the informed consent form for participation in the study, which meets all of the criteria of current FDA regulations.
5. Intact (confirmed by otholaryngological examination) tympanostomy tube(s), inserted no earlier than 3 months prior to randomization to the study due to acute otitis media. Criterion must be met during both, Screening and Baseline physical examination.
6. Judged by an investigator to be in good health as documented by the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), vital sign assessment, and clinical laboratory assessments. Any abnormalities or deviations outside the normal ranges for any of clinical testing (laboratory tests, vital signs) can be repeated at the discretion of the investigator(s) and judged to be not clinically significant for study participation.
7. Demonstrated negative screening test for hepatitis B surface antigen, hepatitis C antibody or HIV antibody (results available in subject’s medical file, performed within previous 3 months are also acceptable).
8. Negative urine pregnancy test in case of post-menarchal females (the day before or on the day of Baseline).

E.4

Principal exclusion criteria

1. Reports receiving any investigational drug within 30 days prior to Baseline visit (dosing).
2. Reports of any presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, urologic, gastrointestinal, hepatic, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease as determined by the investigator(s).
3. Presence of any clinically significant results from laboratory tests, vital signs assessments, as judged by the investigator(s).
4. Signs and symptoms of acute otitis media within 30 days prior to being dosed in the study.
5. Perforated tympanic membrane in other place than tympanostomy tube placement.
6. Current or previous history of any otologic surgery other than insertion/removal of tympanostomy tubes in infected ear.
7. Clinical diagnosis of malignant otitis externa.
8. Mastoid cavities, stenosis, exostosis or tumors of either ear or other noninfectious diseases of either ear.
9. Suspected concurrent fungal or viral infection (e.g. herpes simplex) of either ear.
10. Dermatitis of the infected ear such as psoriasis or seborrhea that would complicate evaluations.
11. Any known hypersensitivity to ciprofloxacin or other carboxyquinolone derivatives, dexamethasone or corticosteroids or other ingredients of the formulation.
12. Receipt of any drug or device as part of a research study within 30 days prior to dosing.
13. Previous participation in this study.
14.Medications:
a) Current or previous use of systemic steroids (within 30 days prior to screening and during screening period) or topical otic steroids (within 2 weeks prior to screening and during screening period).
b) Current or previous otic treatment, topical antibiotics or any other otic product (i.e vinegar, alcohol, etc) within two (2) weeks prior to baseline.
c) Current or previous use of systemic antibiotics within 3 (three) weeks prior to baseline.
15. Demonstrates a positive pregnancy test (if applicable).
16. Demonstrates a positive screening for hepatitis B surface antigen, hepatitis C antibody or HIV antibody.
17. Reports a clinically significant illness during the 30 days prior to Baseline dosing (as determined by the investigator(s)).
18. Reports a history of clinically significant allergies including food or drug allergies.
19. Reports donating blood (1 unit or 350 mL) or plasma (e.g. plasmapheresis) within 30 days prior to Baseline dosing.
20. Demonstrates, in the opinion of study staff, veins unsuitable for repeated venipuncture (e.g. veins difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
21. Use of any prescription drug therapy or over-the-counter (OTC) drugs 7 days prior to receiving study medication.

E.5 End points

E.5.1

Primary end point(s)

Assess the pharmacokinetics bioequivalence of Ciprofloxacin (0.3%) and Dexamethasone (0.1%) to the United States marketed Ciprodex® (ciprofloxacin 0.3% and dexamethasone 0.1%) Sterile Otic Suspension.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 day

E.5.2

Secondary end point(s)

Safety and tolerability in pediatric patients.

E.5.2.1

Timepoint(s) of evaluation of this end point

44+/-4 days

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

Yes

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

Yes

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

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

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:

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)

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