Clinical Trials Register

Summary
EudraCT Number:	2015-003770-32
Sponsor's Protocol Code Number:	CLR_14_05
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:	2016-01-04
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

2015-003770-32

A.3

Full title of the trial

A Randomized, Double-Blind, Four Treatment, Four period, Crossover Study, with Placebo, Tizanidine Immediate Release and Diphenhydramine to Study the Effect of Tizanidine Extended Release on Simulated Driving Performance, Cognitive, and Psychomotor Functioning

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

CLR_14_05

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	Sun Pharma Advanced Research Company
B.1.3.4	Country	India
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	Sun Pharma Advanced Research Company
B.4.2	Country	India
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sun Pharma Advanced Research Company
B.5.2	Functional name of contact point	Shravanti Bhowmik
B.5.3	Address:
B.5.3.1	Street Address	17-B Mahal Industrial Estate, Mahakali Caves Road, Andheri (E)
B.5.3.2	Town/ city	Mumbai
B.5.3.3	Post code	400093
B.5.3.4	Country	India
B.5.4	Telephone number	912266455645
B.5.5	Fax number	912266455685
B.5.6	E-mail	shravanti.bhowmik@sparcmail.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	Tizanidine Extended Release Tablets 12 mg
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	Tizanidine Hydrochloride
D.3.9.1	CAS number	64461-82-1
D.3.9.2	Current sponsor code	Not applicable
D.3.9.3	Other descriptive name	TIZANIDINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04895MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.679
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	Zanaflex Tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Acorda Therapeutics Inc. Ardsley, NY 10502
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.3.1	Product name	Zanaflex Tablets 4 mg
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.3.11 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	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	GALPHARM ONE A NIGHT NIGHTCALM 50MG TABLETS
D.2.1.1.2	Name of the Marketing Authorisation holder	Galpharm Healthcare Ltd, Upper Cliffe Road, Dodworth Business Park, Dodworth, South Yorkshire S75 3S
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	GALPHARM ONE A NIGHT NIGHTCALM 50MG TABLETS (Diphenhydramine Hydrochloride)
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.3.11 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
D.8 Placebo: 2
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 (acute musculoskeletal pain)

E.1.1.1

Medical condition in easily understood language

the trial takes place in healthy subjects

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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 investigate effect of tizanidine ER 12 mg on simulated driving performance, cognitive and psychomotor functions compared with placebo and tizanidine IR 8 mg (two 4 mg doses given 6.5 hours apart) and active control (diphenhydramine) and placebo in healthy subjects

E.2.2

Secondary objectives of the trial

"Not applicable"

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- The potential participant has given informed and written consent and is able to comply with all study assessments scheduled in the protocol
- Healthy males or females aged 21 to 45 years (both inclusive) with body mass index between 18 and 30 kg/m2 and having normal vision
- Possession of a valid Netherlands driver’s license ≥ 3 years with a reported average annual mileage ≥ 5,000 km during the last 3 years
- Any female surgically sterile (bilateral tubal ligation at least 6 months prior, bilateral oophorectomy, or hysterectomy performed) or any female of child bearing potential should be willing to practice an acceptable method of birth control following screening to completion of study of the study. The acceptable contraceptive methods are condoms, diaphragm, intrauterine device (IUD), same sex partner or partner with vasectomy, (note: hormonal contraception is not permitted as it affects tizanidine pharmacokinetics)
- Potential subjects considered healthy based on medical evaluation, electrocardiogram and laboratory values at screening, all lab values are within normal limits or any value out of normal limits considered by the Investigator to be of no clinical significance

E.4

Principal exclusion criteria

- History of allergies or hypersensitivity or intolerance to tizanidine or diphenhydramine
- History or presence of clinically significant or uncontrolled cardiovascular, neurological, psychiatric, hepatic, renal, gastrointestinal, hematological, musculoskeletal or sleep disorder
- History of surgery within 4 weeks of screening
- Clinical lab results suggestive of hepatic impairment (ALT or AST or bilirubin > 2 times of ULN) or renal impairment (creatinine > 2 mg/dL)
- Clinically significant history of alcohol intake (> 21 drinks per week).
- History of drug abuse with drugs used for recreational purpose within one year of the screening visit
- Use of any drug known to induce or inhibit hepatic drug metabolism (specifically CPY1A2 inhibitors, fluoroquinolones, zileuton, antiarrythmics, anti-histamines, ticlopidine, anti-virals, oral contraceptives, anti-depressants and any drugs known to cause change in neurological function) within 14 days of screening to end of study
- Signs or symptoms of narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy or bladder-neck obstruction
- History of participation in an investigational drug study within the past 30 days
- History of excessive caffeine consumption (> 5 cups/day) or smoking (≥10 cigarettes per day) during the last six months prior to screening
- At admission for each period: evidence of pregnancy (urine pregnancy test positive on urine drug screen for women), or demonstrable blood-alcohol concentration (alcohol breath test)
- Pregnant or lactating females

E.5 End points

E.5.1

Primary end point(s)

The primary parameter is the driving simulators measurement of standard deviation lateral position (SDLP) in centimeters at baseline and at four scheduled time points post dose for each treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

day 2,9,16,23. hours t -1.5, t1.5, t3, t5, t7

E.5.2

Secondary end point(s)

Psychomotor Vigilance Task (PVT), Peripheral Detection Task (PDT),Vigilance and (Vigtrack) Tracking Test , 8.1.2.3 Driving simulator parameters (distance headway, time to collision, time headway), subjective repost sleepiness, Karolinska sleep scale

E.5.2.1

Timepoint(s) of evaluation of this end point

day 2,9,16,23. hours t -1.5, t1.5, t3, t5, t7

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

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

Driving safety after administration of medication

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

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)

Yes

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

End of Study (Visit 7, Day 26).
Medical history by means of TNO’s standard medical anamnesis questionnaire
12-lead ECG
Clinical laboratory assessments
General physical and clinical examination
Check and record for use of any concomitant or restricted medication
Assessment for safety, well-being and any adverse event

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)

None

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

2016-01-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-12-15

P. End of Trial
P.	End of Trial Status	Completed

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