Randomised, double-blind, placebo-controlled, active-treatment clinical trial to assess the analgesic efficacy and safety of an oral combination of ibuprofen (arginine) -tramadol HCl administered to patients with moderate to severe pain after undergoing dental surgery.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Farmalider S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

10 Jan 2022 → 22 Jan 2025

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Farmalider S.A.

External identifiers

EU CT number

2024-517807-35-00

EudraCT number

2020-005530-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess whether the combination of ibuprofen (arginine) and tramadol HCl 400/37.5 mg, administered orally every 6 hours to patients presenting moderate to severe pain after dental extraction (third molars), achieves better pain relief, expressed as a difference in the SPID(0-12) hours variable, than its active components administered as monotherapy and compared to placebo.

Secondary objectives 2

1. To describe and compare the following analgesic efficacy parameters obtained in each study treatment group:- Visual Analogue Pain Scale (VAS) score and differences in pain intensity regarding baseline pain (PIDt). - Area Under the Curve of the differences in pain intensity from the start of administration until after 12 hours. - Sum of the differences in pain intensity regarding baseline at 6 hours (SPID0-6h) from the start of administering medication. - Time to first pain relief. - Percentage of patients responding to each treatment. - Demand for each standardised level of rescue medication. - Time elapsed until administration of the rescue medication.
2. Assess the safety and tolerability of each study treatment.

Conditions and MedDRA coding

Moderate to severe somatic pain.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients who provide written informed consent and who are able and willing to comply with all scheduled study visits and procedures
2. Patients ≥ 18 years at screening visit.
3. With a body mass index ≥ 18.5 and < 35 kg / m2 at the screening visit (BMI = weight/height2 = kg/m2).
4. Scheduled for surgical extraction under local anaesthetic, of at least 2 third molars, at least one of them lower, and at least one of them impacted requiring bone removal.* Inclusion criterion 4 will be verified at the screening visit.
5. That they agree not to take analgesics apart from those defined by the protocol as rescue medication and the study medication, 24 hours before the start of surgery until 48 hours after the end of the study medication.
6. Patients who achieve pain on the VAS ≥ 55 mm within the first 3 hours after the end of surgery.**Inclusion criterion 6 will be verified at visit 1 prior to randomisation.

Exclusion criteria 17

1. Patients with a history of allergy or hypersensitivity to study medication, rescue medication, acetylsalicylic acid or any other nonsteroidal anti-inflammatory drug (NSAID) or opioid, or any of their excipients.
2. History of asthma, bronchospasm, urticaria or angioneurotic oedema.
3. Active peptic ulcer, gastrointestinal disorders due to NSAIDs, active gastrointestinal bleeding or history of gastrointestinal bleeding.
4. Haemorrhagic diathesis or other coagulation disorders.
5. Current renal or hepatic insufficiency; or a recent history of moderate or severe impairment of renal, hepatic or cardiac function.
6. Epilepsy.
7. Crohn's disease or ulcerative colitis.
8. Patients who for other reasons should not receive treatment with NSAIDs or tramadol.
9. Patients who, apart from the anaesthetic procedure, cannot abstain from alcohol, psychotropic drugs or sedatives (e.g. benzodiazepines) 72 hours before the start of surgery until 48 hours after the end of the study treatment.
10. History of drug dependency: alcohol, opiates, hypnotics, amphetamines, cocaine, hallucinogens, cannabis or synthetic drugs.
11. Patients who have consumed analgesics, muscle relaxants or anti-inflammatories (including prescription and over-the-counter drugs) 24 hours prior to the start of surgery, or 5 days prior in the case of consumption of COX-2 inhibitors, up to 48 hours after the end of the study medication.
12. Patients in treatment with any other medicinal product that should not be administered due to the risk of adverse interactions with the study medication or interference with the assessments: listed in protocol section 10.2.2 Prohibited medication.
13. Patients who have suffered complications during surgery, a duration of surgery of more than 1 hour or who have required re-anaesthesia (after reaching the appropriate level of anaesthesia).
14. Unresolved infection on the day of surgery if the surgery is severe or requires treatment with systemic antibiotic therapy.
15. Any other disease, relevant laboratory abnormality or condition that, at the discretion of the investigator, could constitute a risk to the participant or interfere with the results of the study (e.g., patients with acute pain of different origin or location at the time of surgery).
16. Patients who have received an experimental drug or used an experimental medical device within 30 days prior to the screening visit.
17. Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Sum of the Pain Intensity Differences from the start of administration until after 12 hours (SPID0-12h), measured through the Visual Analogue Scale (VAS).

Secondary endpoints 11

1. Pain intensity (PI) and pain intensity difference (PID) in scheduled assessment times up to 48 hours from the start of administration of the study medication.
2. Area Under the Curve of pain intensity differences during the first 12 hours of study medication administration.
3. Sum of the pain intensity differences regarding baseline, at 6 hours (SPID0-6h) from the start of the administration of the study medication.
4. Patient responder rate, defined as the percentage of patients with a SPID(0-12h) ≥ δs
5. Time to first pain relief (Pain intensity ↓33%).
6. Proportion of patients using rescue medication.
7. Total use of the different standardised levels of rescue medication from the start of treatment up to 12 and up to 48 hours later (measured in number of rescues required from each level).
8. Time to the first rescue administration from the start of administration of the study medication.
9. Vital signs (body temperature, heart rate and blood pressure) and general physical examination.
10. Laboratory abnormalities.
11. Adverse events.

Investigational products

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

Test 1

Comparator 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Farmalider S.A.

Sponsor organisation

Farmalider S.A.

Address

Calle De La Granja 1 Planta 3

City

Alcobendas

Postcode

28108

Country

Spain

Scientific contact point

Organisation

Farmalider S.A.

Contact name

Carlos Calandria

Public contact point

Organisation

Farmalider S.A.

Contact name

Carlos Calandria

Third parties 1

Locations

1 EU/EEA country · 9 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 5 files

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

Application history

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