Clinical Trials Register

Summary
EudraCT Number:	2020-005278-86
Sponsor's Protocol Code Number:	147(Z)WO20157
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:	2021-10-29
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

2020-005278-86

A.3

Full title of the trial

Efficacy and safety of the combination of ibuprofen and paracetamol versus ibuprofen in monotherapy in
acute Low Back Pain (LBP)

A.3.1

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

Efficacy of the combination of ibuprofen and paracetamol in
acute non-specific LBP

A.4.1

Sponsor's protocol code number

147(Z)WO20157

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	Angelini Pharma S.p.A.
B.1.3.4	Country	Italy
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	Angelini Pharma S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Angelini Pharma S.p.A.
B.5.2	Functional name of contact point	Carmelina Valerio
B.5.3	Address:
B.5.3.1	Street Address	Viale Amelia 70
B.5.3.2	Town/ city	Rome
B.5.3.3	Post code	00181
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390691045567
B.5.5	Fax number	+390678332453
B.5.6	E-mail	carmelina.valerio@angelinipharma.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	Tachifene 500 mg/150 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Aziende Chimiche Riunite Angelini Francesco, ACRAF SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Tachifene 500 mg / 150 mg film-coated tablets
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: 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	Brufen 600 mg film-coated tablet
D.2.1.1.2	Name of the Marketing Authorisation holder	Mylan Italia S.r.l
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Brufen 600 mg film-coated tablet
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Low Back Pain (LBP)

E.1.1.1

Medical condition in easily understood language

Low Back Pain

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10024892
E.1.2	Term	Low back pain (without radiation)
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
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

The primary objective of the study is to assess the pain improvement in patients
with uncomplicated non-specific acute low back pain after a 3-day treatment
period with paracetamol/ibuprofen FDC compared to ibuprofen

E.2.2

Secondary objectives of the trial

A comparison between Group 1 and Group 2 will be performed on the following
secondary objectives:
• the intensity of LBP measured at baseline (Visit 0) and Visit 2
• the daily LBP assessment across the whole study duration
• the degree of improvement in the patient’s mobility restriction,
measured at Visits 0 and 1, 2
• the patient’s functional disability, measured at Visits 0 and 1, 2
• the patients’ global impression about the efficacy of the treatment,
measured at Visit 1 and 2
• the clinical global impression about the efficacy of the treatment, at Visit
1 and 2
• safety and tolerability assessment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients of any ethnic origin between 18 and 64 years
of age (limits included).
2. Patients with uncomplicated and localized acute low back pain or acute
exacerbation of chronic low back pain (not radiating below the gluteal
fold), with moderate/severe pain at baseline. Minimum VAS score ≥ 40
mm at screening visit.
3. Women of childbearing potential and women with no menses for a
period < 12 months must have a negative pregnancy test at Visit 0 and
have to agree not to start a pregnancy from the signature of the
informed consent up to the Final Visit/Visit 2, using an appropriate birth
control method such as combined oestrogen-progestin containing
hormonal contraceptives (e.g., oral, injectable, transdermal), progestinonly hormonal contraceptives (e.g., oral, injectable, implantable),
intrauterine device (IUD) or Intrauterine hormone-releasing System
(IUS) in combination with male condom, bilateral tubal occlusion,
vasectomised partner, sexual abstinence. The following definitions will
be considered:
• Woman of childbearing potential (WOCBP): i.e., fertile,
following menarche and until becoming post-menopausal,
unless permanently sterile. Permanent sterilization methods
include hysterectomy, bilateral salpingectomy and bilateral
oophorectomy.
• A postmenopausal state is defined as no menses for 12 months
without an alternative medical cause.
4. Patients legally capable of giving their consent to participate in the study
and available to sign and date the written informed consent.

E.4

Principal exclusion criteria

1. Known hypersensitivity or allergy to the active ingredients and/or to any component of the study medications.
2. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
3. Lactating and pregnant women.
4. Clinically significant abnormalities on physical examination, vital signs or laboratory tests at Visit 0 which in the opinion of the Investigator could interfere with the study procedures or endpoints evaluation.
5. Suspicious or confirmed COVID-19 infection at time of screening visit.
6. History of cervical, thoracic, or lumbosacral pain for ≥75% of the time in the last year, or of any other LBP episode in the last 3 months that
required pharmacological treatment with an opioid analgesic.
7. Patients with: • serious spinal pathology; spinal surgery in the year
prior to screening or history of more than one spinal surgery; history of severe lumbar spinal stenosis; ankylosing spondylitis; lumbosciatalgia; herniated disc or radiculopathy; severe arthritis and osteoporosis; muscular diseases, such as myositis, poliomyelitis, muscular dystrophy and myotonia; fibromyalgia; myasthenia grave; fracture or recent history of violent trauma of the back; serious structural deformity of the back;
• history of hypersensitivity to aspirin or any other NSAIDs; suspicion of inflammatory, infective or neoplastic cause of pain; non- specific back symptoms related to abdominal, pelvic or thoracic pathology sensory and/or motor deficits in lower extremities • history of gastroduodenal ulcer or bleeding • history of severe cardiac, hepatic or renal insufficiency • current anticoagulant therapy • previous treatment with anticoagulants in the seven days before the screening visit •concomitant use of physical or alternative therapies to treat current episode of pain • local steroid injection for LBP treatment within previous 30 days •local steroid injection for any reasons within previous 15 days • alcohol or drug-addition or abuse • cancer, not in remission or in remission less than 1 year • active influenza or other viral syndrome; immunosuppression; systematically unwell; unexplained significant
weight loss • widespread neurological symptoms (including cauda
equina syndrome) or any brain disease; ever suffered from any brain
damage or have been in a coma; epilepsy or seizure • active or
suspected oesophageal, gastric, pyloric channel, or duodenal ulceration, or bleeding in the last 30 days• blood-formation disturbance • renal
and/or hepatic failure • acute hepatitis • acetylsalicylic acid-triggered
asthma; • history of asthma; • glucose-6-phosphate dehydrogenasedeficient
patients; glutathione deficiency, dehydration, chronic
malnutrition; anaemia. Any other condition that, in the opinion of the Investigator, interferes with the study endpoints/procedures and does
not justify the inclusion of the patient in the study.
8. current use of full, regular, recommended doses of any skeletal
muscle relaxants/non – opioid analgesics/anti-inflammatory/NSAIDs in the 6 hours prior to the screening visit and/or any medication that can alter the perception of pain (e.g. opioids, heparinoids, psychotropic agents, systemic corticosteroids, anti-H1 agents, or
glucocorticosteroids, etc.), in the 24 hours prior to the screening visit.
Use is forbidden for the entire trial duration, with the exception of
therapeutic doses of benzodiazepines used as hypnoinducers in patients stabilised for more than one month from the screening visit
9. current use of the following medications (use is forbidden for the
entire trial duration): • metoclopramide • propantheline •
chloramphenicol tacrolimus, ciclosporin, aminoglycosides and quinolone antibiotics • voriconazole and fluconazole (CYP2C9 inhibitors) •probenecid • zidovudine • co-trimoxazole • anticoagulants • antiplatelet agents • anticonvulsants • ACE inhibitors, beta-blockers, angiotensin II receptor blockers and diuretics • methotrexate •antidiabetic drugs (i.e. sulphonylureas) • cardiac glycosides (digoxin and digitotoxin) • lithium •cholestyramine • isoniazid, rifampin, pyrazinamide and ethambutol • baclofen • ginkgo biloba • acetylsalicylic acid
10. Patients treated with invasive procedures aimed to reduce LBP (e.g., epidural injections, spinal cord stimulation therapy).
11. History of alcoholic/substance abuse. Use of alcohol is forbidden
during the entire duration of the study.
12. Inability to comply with the protocol requirements, instructions or study-related restrictions (i.e., uncooperative attitude, inability to return for study visits, unlikelihood of completing the clinical study); vulnerable patients (i.e., persons kept in detention).
13. Patients involved in the conduct of the study (i.e., Investigator or
his/her deputy, first grade relatives, pharmacist, assistant or other
personnel).
14. Participation to an interventional clinical trial within 3 months prior to Visit 0.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint will be the area under the pain intensity difference-versus-time curve of LBP scores
up to 3 days of treatment [SPID 0-3 days]. The pain intensity difference will be considered the difference in
VAS pain intensity between one time-point and the baseline. The sum of the pain intensity differences
(SPID) will be the sum of the average of two consecutive pain intensity differences multiplied by the time interval between two time points.

E.5.1.1

Timepoint(s) of evaluation of this end point

after 3 days of medication

E.5.2

Secondary end point(s)

The secondary endpoints of the study will be:
• Change in VAS score at baseline (Visit 0) and at the end of study (Visit 2)
• Change from baseline up to the end of the study in VAS score, assessed at baseline (Visit 0) and
Visit 2, and daily recorded in the patient diary during the whole home-stay period
• Change from baseline up to the end of the study in the hand-to-floor distance assessed at Visits 0,
1 and 2, measured by a cm graduated bar
• Change from baseline up to the end of the study in the in the degree of improvement in the
functional disability, assessed at Visits 0, 1 and 2, measured by the Oswestry Disability Index (ODI)
• Change in the patients’ global impression at Visits 1 and 2, measured by the Patients’ Global
Impression of Change (PGIC) scale
• Change in the clinical global impression at Visits 1 and 2, measured by the Clinical Global
Impression-Improvement (CGI-I) scale
• Safety and tolerability assessment

E.5.2.1

Timepoint(s) of evaluation of this end point

from Visit 0 to Visit 2

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

Yes

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

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

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

ibuprofen 600 mg

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

V2 (Day 8 +/- 1 day).

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

E.8.9.2

In all countries concerned by the trial months

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:

176

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

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

176

F.4.2.2

In the whole clinical trial

176

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

2021-06-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-10-05

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