Clinical Trials Register

Summary
EudraCT Number:	2012-005492-13
Sponsor's Protocol Code Number:	TMC207TBC1002
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-07
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

Netherlands - Competent Authority

A.2

EudraCT number

2012-005492-13

A.3

Full title of the trial

A Phase I, open-label, randomized, 3-way crossover study in 3 Panels of healthy, adult subjects to assess the relative bioavailability of TMC207 following single-dose administration of two pediatric formulations using a 100 mg tablet formulation as the reference, with and without food.

A.3.1

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

A.4.1

Sponsor's protocol code number

TMC207TBC1002

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/55/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen infectious diseases BVBA
B.1.3.4	Country	Belgium
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	Janssen Research and Development, LLC
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	Janssen-Cilag International NV-Clinical Registry Group
B.5.2	Functional name of contact point	Janssen-Cilag International NV
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	233CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3171524166
B.5.5	Fax number	+3171524110
B.5.6	E-mail	clinicaltrialsEU@its.jnj.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	Yes
D.2.1.1.1	Trade name	Sirturo
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen Research & Development, LLC
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/314
D.3 Description of the IMP
D.3.1	Product name	TMC207 (as fumaric acid salt)/bedaquiline
D.3.2	Product code	F001
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
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	bedaquiline fumarate
D.3.9.1	CAS number	845533-86-0
D.3.9.2	Current sponsor code	TMC207
D.3.9.3	Other descriptive name	JNJ-16175328-AEP, R403323
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	100
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	TMC207 (as fumaric acid salt)/bedaquiline
D.3.2	Product code	G003
D.3.4	Pharmaceutical form	Tablet for oral suspension
D.3.4.1	Specific paediatric formulation	No
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	bedaquiline fumarate
D.3.9.1	CAS number	845533-86-0
D.3.9.2	Current sponsor code	TMC207
D.3.9.3	Other descriptive name	JNJ-16175328-AEP
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	20
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	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	TMC207 (as fumaric acid salt)/bedaquiline
D.3.2	Product code	G004
D.3.4	Pharmaceutical form	Granules for oral solution
D.3.4.1	Specific paediatric formulation	No
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	bedaquiline fumarate
D.3.9.1	CAS number	845533-86-0
D.3.9.2	Current sponsor code	TMC207
D.3.9.3	Other descriptive name	JNJ-16175328-AEP
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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

Multi-drug resistant tuberculosis

E.1.1.1

Medical condition in easily understood language

Tuberculosis

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10044755
E.1.2	Term	Tuberculosis
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

The primary objective is to assess the relative bioavailability of TMC207 after single-dose administration of 100 mg of TMC207 as water dispersible tablets or granules using a 100-mg tablet formulation as the reference, with and without food.

E.2.2

Secondary objectives of the trial

1) To determine the pharmacokinetics of the primary metabolite, M2, after single-dose administration of TMC207 under fed and fasted conditions in healthy adult subjects;
2) To determine the food-effect for each of the formulations (cross-panel comparison);
3) To evaluate the short-term safety and tolerability of TMC207 following administration of 3 single oral doses under fed and fasted conditions in healthy adult subjects;
4) To evaluate the taste perception of the pediatric formulations;

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Healthy participant on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG), and the results of blood biochemistry and hematology tests and a urinalysis performed at screening
2)Must have a Body Mass Index (BMI, weight in kg divided by the square of height in meters) of 18.5 to 30.0 kg/m2, extremes included
3)Women must be postmenopausal for at least 2 years
4) Men must agree to use a highly effective method of birth control (i.e., male condom with either female intrauterine device, diaphragm, cervical cap or hormone based contraceptives by their female partner) when having sexual intercourse with a female partner of childbearing potential, and to not donate sperm during the study and for 6 months after receiving the last dose of study drug. Men who have had a vasectomy and have a female partner of childbearing potential must agree to use a male condom during the study and for 6 months after receiving the last dose of study drug -Participants must be non-smokers for at least 3 months prior to screening
5) Participants must be non-smokers for at least 3 months prior to screening

E.4

Principal exclusion criteria

1) Human immunodeficiency virus – type 1 (HIV-1) or type 2 (HIV-2) infection confirmed at screening -Hepatitis A, B or C infection confirmed at screening
3) A positive urine drug test or alcohol breath test at screening. Urine will be tested for the presence of amphetamines, barbiturates, benzodiazepines, cocaine, methadone, and opioids
4) History or any currently active disease or condition that the Investigator considers to be clinically significant for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified ssessments

E.5 End points

E.5.1

Primary end point(s)

Protocol-specified pharmacokinetic parameters will be determined from plasma samples collected after each administration of study drug to assess the relative bioavailability of TMC207.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 72 hours after study drug intake during 3 treatment sessions

E.5.2

Secondary end point(s)

1) Protocol-specified pharmacokinetic parameters will be determined from plasma samples collected after each administration of study drug to assess the concentration of the primary metabolite in TMC207
2) The effect of food will be determined by comparing, across panels, each formulation taken after eating a standardized breakfast versus after eating yoghurt, and versus no food (ie, in the fasted state).
3) The number of participants reporting adverse events as a measure of safety and tolerability.Includes up to 30-32 days after the last plasma sample in the last treatment session for participants who complete the study (or up to 30-32 days after a participant withdraws from the study).
4) The taste of each formulation will be assessed by having study participants complete a 5-item questionnaire after they take study drug.

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Up to 72 hours after each study drug intake during 3 treatment sessions
2) Up to 72 hours after study drug intake during 3 treatment sessions
3) Up to approximately 12.5 weeks
4) On Day 1 after study drug administration during 3 treatment sessions.

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

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

bioavailability, tolerability, food-effect,taste perception

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

Yes

E.7.1.3.1

Other trial type description

Bioavailability

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

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

Yes

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

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:

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

F.3.3

Specific vulnerable populations

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

There are no plans for treatment or standard of care after participation in the trial.

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

2013-03-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-08-26

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