A double blind, double dummy, multicenter, randomized, placebo- and active-controlled clinical trial to evaluate effectiveness of Tricortin 1000 in patients affected by chronic low back pain

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fidia Farmaceutici S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

20 Feb 2019 → ongoing

Decision date (initial)

2024-12-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Fidia Farmaceutici S.p.A.

External identifiers

EU CT number

2024-512292-12-00

EudraCT number

2018-002003-33

ClinicalTrials.gov

NCT04585334

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate superiority of Tricortin 1000 over placebo in improvement in pain relief as change from baseline to 15 days in patients with chronic low back pain (LBP) and acute exacerbation at study entry.

Secondary objectives 2

1. To compare Tricortin 1000 and diclofenac sodium medicated plaster (Itami®) in improvement in pain relief as change from baseline to 15 days in patients with chronic LBP and acute exacerbation at study entry.
2. To compare Tricortin 1000 with placebo and diclofenac sodium medicated plaster in functional disability improvement, clinical improvement, patient global assessment (PGA), clinical global impression (CGI), consumption of rescue medication, patient safety as change from baseline to 15 days.

Conditions and MedDRA coding

Low Back Pain

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Clinical diagnosis of chronic mechanical (mild, moderate degenerative process of disc and facet) chronic LBP, for at least 3 months but no more than 6 months, confirmed (thanks to instrumental analysis obtained within 9 months before the Screening visit) by CT or MRI. In case a MRI/CT performed in the previous 9 months is not available, the diagnosis should be confirmed by means of a MRI performed between Screening visit (Visit 1) and Baseline visit (Visit 2).
2. A moderate to severe acute exacerbation of chronic LBP at study entry, defined as a score ≥4 and ≤8 rated on the NRS-11
3. Age greater than or equal to 40 and less than or equal to 70 years
4. Patient able to maintain a Diary during the study
5. Patient with a Body Mass Index (BMI) < 30 kg/m2
6. Discontinuation of any analgesic/NSAID therapy, opioids, corticosteroids, skeletal muscle relaxants and any other medication or non-pharmacological therapy (if it would interfere with the study assessments), with the exception of paracetamol, with no intent to resume during study
7. Patients who did not receive antidepressant medications and/or benzodiazepines for at least 60 days
8. Patient able to read and understand the language and content of the study material, understand the requirements for follow-up visits, is willing to provide information at the scheduled evaluations and is willing and able to comply with the study requirements
9. Patient has undergone the informed consent process and has signed an approved consent form
10. If female, patient must have a negative urine pregnancy test and use a highly effective form of contraception for a least one month prior to screening and throughout the study; or females must be surgically sterile, or postmenopausal as documented in medical history for at least one year. Highly effective birth control methods include: combined hormonal contraception (containing estrogen and progestogen) associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence
11. Patients who did not use Tricortin 1000 in the past to treat LBP or other pathological conditions

Exclusion criteria 32

1. Patients suffering of chronic non-specific LBP
2. Participation in another research study
3. History of epilepsy
4. Patients who have an unstable psychiatric condition
5. Unexplained serious thoracic pain
6. Any recent trauma, which may raise the possibility of a fracture
7. Fever and unexplained weight loss
8. Bladder or bowel dysfunction
9. Females who are pregnant or breast-feeding
10. Patients who are not able to give informed consent
11. Patients who cannot commit to the entire duration of the study
12. Patients with back pain referred from a mechanical cause (except for mild, moderate degenerative process of disc and facet) non spinal source or back pain associated with another specific spinal cause
13. Patients who have a primary bone disease, cancer, infection (except for osteoporosis patients without fracture history)
14. Other conditions which may confound the interpretation of the study, such as rheumatoid arthritis, severe venous diseases, peripheral arterial diseases, transient ischemic attack, stroke, current symptoms of coronary artery disease
15. History of narcotic abuse at any time in the past and/or drug or alcohol abuse in the past year
16. Patients who have had a previous treatment with physical therapy for LBP in the last 4 weeks before the screening visit or are going through a course of physical therapy or chiropractic treatment at the time of planned enrolment
17. History of carcinoma
18. Progressive neurological deficit
19. Disturbed gait, saddle anaesthesia
20. Radicular syndromes of idiopatic, metabolic, toxic, infective, demyelinating or neoplastic aetiology
21. Patients with spondylolisthesis, spondylolysis or ankylosing spondylitis
22. Patients with scoliosis of 15° or more
23. Patients with inflammatory arthritis or severe degenerative process of disc and facet
24. Patients who have had prior spine surgery, including rhizotomy as like as, patients who are planning or have been advised to have spine surgery
25. Patients with any concomitant chronic disease(s) or condition(s) that may predispose them to a high probability of interfering with the completion of the follow-up of the study such as peptic ulcer, liver disease, severe coronary disease, renal disease, cancer, pregnancy, alcoholism, mental state, or other clinically significant condition
26. Patients with history of active or suspected oesophageal, gastric, pyloric channel, or duodenal ulceration or bleeding in the last 12 weeks before the screening visit
27. Patients requiring chronic use of analgesia for pain
28. Patients with known allergies or hypersensitivity or intolerance to Tricortin 1000, NSAIDs and/or paracetamol, and/or to active or inactive excipients of formulation
29. Patients in treatment with neuroleptics (antipsychotics)
30. Patients affected by diabetic neuropathy, multiple sclerosis or Amyotrophic Lateral Sclerosis
31. Any contraindications to either prone distraction or side posture manipulation
32. Any contraindications as reported in the Patient Information Leaflet of Tricortin 1000 or Diclofenac sodium medicated plaster

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline to Day 15 in NRS-11

Secondary endpoints 5

1. LBP related disability improvement measured through the Oswestry Low Back Pain Disability Index (ODI), version 2.1a, at baseline visit and then in the following visits: V3-Day 7 and V4-Day 15.
2. Clinical improvement evaluated at baseline visit and then at V3-Day 7 and V4-Day 15 through the following parameters: Range of Motion testing, Joint reflex changes (ROT), Lasegue’s test (passive straight leg raise), Femoral stretch test (Wasserman test), Dandy’s sign, Valleix’s points pressure
3. PGA and CGI of the status of LBP evaluated at baseline visit and then in the following visits: V3-Day 7 and V4-Day 15
4. Daily rescue medication required for pain relief
5. Safety of daily intramuscular Tricortin 1000 injections and of twice daily diclofenac sodium medicated plaster applications evaluated by physical examination, vital signs and by tracking the number of patient withdrawals and their adverse events at each visit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fidia Farmaceutici S.p.A.

Sponsor organisation

Fidia Farmaceutici S.p.A.

Address

Via Ponte Della Fabbrica 3 A

City

Abano Terme

Postcode

35031

Country

Italy

Scientific contact point

Organisation

Fidia Farmaceutici S.p.A.

Contact name

Corporate Clinical & Preclinical Development

Public contact point

Organisation

Fidia Farmaceutici S.p.A.

Contact name

Corporate Clinical & Preclinical Development

Third parties 2

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications