Phase III, double-blind, randomised, placebo- and active treatment-controlled clinical trial to evaluate the analgesic efficacy and safety of a combination of ibuprofen (arginate)-tramadol hydrochloride 400-37.5 mg, administered intravenously to patients with acute severe postoperative pain.

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

6 Feb 2024 → ongoing

Decision date (initial)

2023-09-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Laboratorios Farmalíder, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess whether the fixed-dose combination of ibuprofen (arginate)-tramadol hydrochloride 400-37.5 mg IV/4 hours, administered post-operatively to patients with severe pain, achieves non-inferior pain control at 4 h as compared to the administration of 100 mg of tramadol alone and better pain control than placebo.

Secondary objectives 8

1. To assess whether the fixed-dose combination of ibuprofen (arginate)-tramadol hydrochloride 400-37.5 mg IV/4 hours, administered post-operatively to patients with severe pain, achieves non-inferior pain control at 8 hours as compared to the administration of 100 mg of tramadol alone and better pain control as compared to placebo.
2. To evaluate the outcome of the following parameters compared to placebo and tramadol (100 mg): Numeric Pain Scale (NRS) score and Pain Intensity Differences with respect to baseline pain (PID) 4 and 8 hours after starting treatment.
3. To assess the time to first pain relief from the scheduled assessment times.
4. To calculate the percentage of responders to each treatment.
5. To calculate the percentage of patients using rescue medication in the first 8 hours.
6. To assess the time to administration of rescue medication.
7. To assess the total amount of rescue medication used by each treatment group.
8. To assess the safety and tolerability of each study treatment.

Conditions and MedDRA coding

Acute pain

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients who grant written informed consent (IC) and who are able to comply with the scheduled study procedures. Informed consents obtained verbally during the telephone consultation, documented in the medical record and signed by patients at the next visit to the study site will be accepted.
2. Patients aged ≥ 18 years at the screening visit.
3. Patients with body mass index ≥ 18.5 and < 40 kg/m2 at the screening visit.
4. Patients scheduled for open or laparoscopic surgery for myomectomy, total or partial hysterectomy due to benign conditions, oophorectomy, salpingo-oophorectomy, cholecystectomy, haemorrhoidectomy or tonsillectomy.
5. Patients with an American Society of Anesthesiologists (ASA) anaesthesia risk score of I or II.
6. After surgery and prior to randomisation: Patients with a Numeric Rating Scale (NRS) for pain score of ≥ 6 after surgery.

Exclusion criteria 13

1. Patients with a history of allergy or hypersensitivity to the study medication, rescue medication or any of the excipients.
2. History of bronchospasm, asthma, rhinitis, angioedema or urticaria associated with the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
3. Active or recurrent peptic ulcer and/or gastrointestinal bleeding, or a history of gastrointestinal bleeding or perforation related to previous treatment with NSAIDs.
4. Bleeding diathesis or coagulation disorders.
5. Patients with moderate or severe renal, liver or heart failure (New York Heart Association [NYHA] class III-IV).
6. Patients with uncontrolled epilepsy.
7. History of dependence on drugs of abuse: alcohol, opiates, hypnotics, amphetamines, cocaine, hallucinogens, cannabis or synthetic drugs of abuse.
8. Patients under treatment with any medicinal product that should not be administered due to the risk of adverse interactions with the study drug or interference with the study assessments (indicated in section 9.1.10. of the protocol “Prohibited Medication”).
9. A surgical procedure during the study other than that initially planned or lasting more than 4 hours, and which in the investigator’s opinion could have an impact on the degree or type of post-operative pain and the analgesic response, thereby interfering with the interpretation of the study results.
10. Serious unresolved infection on the day of surgery.
11. Any other disease, relevant laboratory test alteration or condition which in the investigator’s opinion could interfere with the results of the study or constitute a risk for the subject if he/she participates in the study.
12. Patients currently enrolled in or who have participated in a clinical trial with medicinal products or devices in the 30 days prior to the screening visit.
13. Women who are pregnant or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Sum of Pain Intensity Differences from the start of administration to 4 hours (SPID0-4h) , measured using the Numeric Rating Scale for Pain at baseline, 1 h, 2 h, 3 h and 4 h.

Secondary endpoints 10

1. Efficacy assessment: - Sum of Pain Intensity Differences from the start of administration to 8 hours (SPID0-8h), measured using the Numeric Pain Scale at baseline, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h and 8 h.
2. Pain intensity measured using the Numeric Pain Scale at baseline, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h and 8 h after the start of treatment.
3. Pain intensity difference (PID) at 4 and 8 hours from the start of administration of the study medication.
4. Time to first pain relief (↓33% pain), from the scheduled assessment intervals.
5. Responder rate, defined as the percentage of patients with an SPID(0-4h) ≥δs.
6. Percentage of patients using rescue medication.
7. Time to first administration of rescue medication from the start of administration of the study medication.
8. Total rescue medication use from start of treatment to 8 hours (measured in number of rescue doses required).
9. Safety assessment: Vital signs (body temperature, heart rate, blood pressure and oxygen saturation).
10. Safety assessment: Adverse events.

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

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 · 12 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 6 files

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

Application history

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