Clinical Trials Register

Summary
EudraCT Number:	2015-002875-20
Sponsor's Protocol Code Number:	KCT03/2015–DORETA
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-07-19
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2015-002875-20

A.3

Full title of the trial

Efficacy and Safety of Prolonged Release (SR) Tramadol Hydrochloride (HCl)/Paracetamol fixed combination and Immediate Release (IR) Tramadol HCl/Paracetamol fixed combination in Patients with Moderate to Severe Acute Low-Back Pain - TreaSuRe

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

KCT03/2015–DORETA

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	Krka d.d., Novo mesto
B.1.3.4	Country	Slovenia
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	Krka d.d., Novo mesto
B.4.2	Country	Slovenia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	KRKA - POLSKA Sp. z o.o.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Równoległa 5
B.5.3.2	Town/ city	Warsaw
B.5.3.3	Post code	02-235
B.5.3.4	Country	Poland
B.5.4	Telephone number	0048609528480
B.5.6	E-mail	magdalena.falandysz-kasperska@krka.biz

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	Doreta
D.2.1.1.2	Name of the Marketing Authorisation holder	KRKA, d. d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Słovenia
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	Doreta
D.3.4	Pharmaceutical form	Film-coated 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	tramadol
D.3.9.3	Other descriptive name	TRAMADOL HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04927MIG
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	37.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	paracetamol
D.3.9.3	Other descriptive name	PARACETAMOL
D.3.9.4	EV Substance Code	SUB09611MIG
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	325
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	Doreta SR
D.2.1.1.2	Name of the Marketing Authorisation holder	KRKA, d. d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Słovenia
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	Doreta SR
D.3.4	Pharmaceutical form	Prolonged-release 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	tramadol
D.3.9.3	Other descriptive name	TRAMADOL HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04927MIG
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	75
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	paracetamol
D.3.9.3	Other descriptive name	PARACETAMOL
D.3.9.4	EV Substance Code	SUB09611MIG
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	650
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

Moderate to severe acute low-back pain (12 weeks or less of symptoms).

E.1.1.1

Medical condition in easily understood language

Moderate to severe acute low-back pain (12 weeks or less of symptoms).

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10024891
E.1.2	Term	Low back pain
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Main objective of the trial is to evaluate the efficacy, safety and effects on Quality of Life (QOL) of the medicines Doreta IR and Doreta SR produced by Krka, d.d., Novo mesto, Slovenia in patients with moderate to severe acute low-back pain.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients diagnosed with acute low back pain (12 weeks or less of symptoms).
• Patients whose average pain intensity is more than or equal to 40 millimeters on horizontal Visual Analog Scale (VAS) over the last 48 hours after the completion of screening.
• Female and male patients aged 18-75 years.
• Written informed consent.

E.4

Principal exclusion criteria

• Hypersensitivity to the active substances or to any of the excipients.
• Patients taking Monoamine oxidase (MAO) inhibitors or are within two weeks of their withdrawal.
• Patients taking neuroleptics or drugs for seizures.
• Severe hepatic impairment.
• Patients on maintenance tramadol and/or paracetamol therapy.
• Patients taking sedative hypnotics, short-acting analgesics, topical medications and anesthetics, and/or muscle relaxants.
• Pregnant, lactating or breastfeeding participants.
• Known or suspected alcohol or drug abuse or addiction within three years preceding screening.
• Patients with unstable angina pectoris or after acute myocardial infarction (4 weeks after acute myocardial infarction).
• Other mental disorders (possible interactions with mental disorder medicines).
• Surgical procedures planned to occur during trial (patients may be rescreened following completion of and recovery from the surgical procedure).
• Concomitant treatment that might influence the final therapeutic effect of the tested active substances.
• Concomitant therapy with either selective serotonin reuptake inhibitors (SSRI) or serotonin–norepinephrine reuptake inhibitors (SNRI).
• Patients who under the opinion of the investigator will not be compliant to the treatment.

E.5 End points

E.5.1

Primary end point(s)

The proportion of patients with clinically meaningful improvement of low back pain. Reduction of low back pain intensity is considered as clinically meaningful if pain intensity not exceeding 30 mm on VAS is achieved on the day of therapy discontinuation or at the end of the trial.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 28 days of treatment

E.5.2

Secondary end point(s)

The secondary end points of the trial are:
• Pain intensity difference (PID) at the end of dosing interval on day 6 (one endpoint).
• Cumulative pain intensity (CPI) throughout the dosing interval (five endpoints).
• Pain intensity difference between each control visit value and the baseline value at Visit 1 (three endpoints).
• Quality of life difference (two endpoints).
• Pain interference score difference (assessed by Brief pain inventory - Short form) between the value at each visit and the baseline value at Visit 1 (three endpoints).
• Proportion of patients with excellent pain response (one endpoint).
• Proportion of patients with reduced pain at each control visit (three endpoints).
• Proportion of patients with eliminated pain: at each control visit (three endpoints).
• Proportion of compliant patients, i.e. those having a compliance of more than 80 % at the regular therapy end visit (one endpoint).

E.5.2.1

Timepoint(s) of evaluation of this end point

After 28 days of treatment

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

Yes

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

Yes

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)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Different dosage forms and doses of the tramadol/paracetamol combination

E.8.2.4

Number of treatment arms in the trial

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

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

E.8.9.2

In all countries concerned by the trial years

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:

300

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

F.3.2

Patients

Yes

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.4.2

For a multinational trial

F.4.2.1

In the EEA

350

F.4.2.2

In the whole clinical trial

350

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
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	KRKA-POLSKA SP. Z O.O.
G.4.3.4	Network Country	Poland

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-09-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-08-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-12-18

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