Clinical Trials Register

Summary
EudraCT Number:	2014-001545-25
Sponsor's Protocol Code Number:	CHDR1409
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-05-22
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

Netherlands - Competent Authority

A.2

EudraCT number

2014-001545-25

A.3

Full title of the trial

Randomized, double-blind, placebo-controlled, three way crossover, double dummy, single centre study evaluating the effect of haloperidol 2 mg and lorazepam 1 mg on posturography and underlying systems involved in standing balance in 12 healthy elderly subjects.

A.3.1

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

Studying the effect of haldol and lorazepam on standing balance measured with the BalRoom in healthy elderly.

A.3.2

Name or abbreviated title of the trial where available

BalRoom study

A.4.1

Sponsor's protocol code number

CHDR1409

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	Centre for Human Drug Research
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Centre for Human Drug Research
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Centre for Human Drug Research
B.5.2	Functional name of contact point	J.M.A. van Gerven
B.5.3	Address:
B.5.3.1	Street Address	Zernikedreef 8
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CL
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715246 400
B.5.5	Fax number	+31715246 499
B.5.6	E-mail	clintrials@chdr.nl

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	Haloperidol
D.2.1.1.2	Name of the Marketing Authorisation holder	Generic
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	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	haloperidol
D.3.9.1	CAS number	52-86-8
D.3.9.3	Other descriptive name	HALOPERIDOL
D.3.9.4	EV Substance Code	SUB08005MIG
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
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	Yes
D.2.1.1.1	Trade name	Lorazepam
D.2.1.1.2	Name of the Marketing Authorisation holder	Generic
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	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	lorazepam
D.3.9.3	Other descriptive name	LORAZEPAM
D.3.9.4	EV Substance Code	SUB08582MIG
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
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

Healthy volunteers (balance disorders)

E.1.1.1

Medical condition in easily understood language

Healthy volunteers (balance disorders)

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10049848
E.1.2	Term	Balance disorder
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10004070
E.1.2	Term	Balance difficulty
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 assess the effect of haloperidol compared to placebo on stability (Body Sway) in relation to stabilizing subsystems (BalRoom) in healthy elderly.
• To assess the effect of lorazepam compared to placebo on stability (Body Sway) in relation to stabilizing subsystems (BalRoom) in healthy elderly.
• To assess the effect of lorazepam compared to haloperidol on stability (Body Sway) in relation to stabilizing subsystems (BalRoom) in healthy elderly.
• To assess the relationship between BalRoom and NeuroCart subtests in healthy elderly.
• To assess the sensitivity of BalRoom and NeuroCart parameters for drug effects in healthy elderly.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Healthy male and/or female subjects over the age of 70 years (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests).

2. Body Mass Index (BMI) of 17.5 to 35 kg/m2; and a total body weight => 50 kg.

3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

4. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

5. Mini-Mental Status Examination (MMSE) score > 26 at screening

E.4

Principal exclusion criteria

1. Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

2. Subjects presenting with orthostatic hypotension, in which orthostatic hypotension is defined as a decrease of 20 mmHg for systolic blood pressure or 10 mmHg for diastolic blood pressure 2 minutes after standing from a supine position.

3. Any condition possibly affecting drug absorption (eg, gastrectomy).

4. A positive urine drug screen.

5. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of Screening.

6. Treatment with an investigational drug within 3 months prior to screening or having participated in more than 4 investigational drug studies within 1 year prior to screening.

7. Use of (non-)prescription medications that are believed to affect subject safety or the overall results of the study following judgment by the investigator.

8. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.

9. Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.

10. Physically unable to perform BalRoom tests, e.g. walking and standing tests.

11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

12. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects directly involved in the conduct of the study.

13. Clinical significant abnormalities on ECG and or QTcf > 500ms.

E.5 End points

E.5.1

Primary end point(s)

1. Pharmodynamics:
BalRoom assessment:
• Sensory weights (weighting factors of proprioceptive, visual and vestibular system).
• Active dynamics of ankle joint (time delay (s), active stiffness (Nm/rad) and active damping (Nm/rad/s)).
• Active dynamics of hip joint (time delay (s), active stiffness (Nm/rad) and active damping (Nm/rad/s)).
• Force feedback (time constant (s) and stiffness (Nm/rad ))
• Passive dynamics of ankle joint (passive stiffness (Nm/rad) and passive damping (Nm/rad/s)).
• Passive dynamics of hip joint (passive stiffness (Nm/rad) and passive damping (Nm/rad/s)).

Neurocart assessment:
• Saccadic Eye Movements (saccadic reaction time, saccadic peak velocity (deg/sec), and saccadic inaccuracy).
• Body Sway (antero-posterior sway (mm/2min)).
• Smooth Pursuit (percentage of time the eyes of the subjects are in smooth pursuit of the target (%)).
• Bond and Lader VAS (alertness, calmness, mood subscales (mm)).
• Bowdle VAS (internal & external perception, feeling high )(mm))
• Adaptive Tracking (%).
• Pharmaco-EEG ((α, β, δ, γ and θ power)

Short Phsyical Performance Battery:
• Ability to maintain standing balance during 10 seconds in the several standing positions
• 4-meter walking speed (m/s)
• Sit-to-stand transfer time (s)

Other:
• Serum prolactin concentrations
• Handgrip strength (kg)

2. Pharmacokinetics of lorazepam and haloperidol
• Cmax, Tmax, AUClast, AUC24, AUCinf, CL/F, Vz/F, t1/2.

3. Tolerability / safety
Adverse events, vital signs measurements, 12-lead ECGs, physical examination findings and clinical safety laboratory measurement.

E.5.1.1

Timepoint(s) of evaluation of this end point

Various time points

E.5.2

Secondary end point(s)

2. Pharmacokinetics of lorazepam and haloperidol
• Cmax, Tmax, AUClast, AUC24, AUCinf, CL/F, Vz/F, t1/2.

3. Tolerability / safety
Adverse events, vital signs measurements, 12-lead ECGs, physical examination findings and clinical safety laboratory measurement.

E.5.2.1

Timepoint(s) of evaluation of this end point

Various time points

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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)

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

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

Last subject, 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

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)

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

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)

Not applicable

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

2014-05-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-02

P. End of Trial
P.	End of Trial Status	Ongoing

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