Evaluation of the Analgesic Efficacy and Safety of DFL24412 Versus Ketoprofen Lysine Salt in Patients with Chronic Low Back Pain
- Trial ID
- 2024-513940-27-00
- Sponsor
- Dompe' Farmaceutici S.p.A.
Trial statistics
Objectives
The primary objective of this phase 2, multicenter, randomized, double-blind, active-controlled, parallel-group study is to evaluate the **efficacy** of DFL24412 at doses of 80 mg-34 mg and 40 mg-17 mg administered orally in patients with **chronic low back pain** compared to Ketoprofen Lysine Salt (KLS) at a dose of 80 mg, specifically at week 1. This evaluation is clinically relevant as it aims to determine the potential of DFL24412 as an effective treatment option for managing chronic low back pain, a condition that significantly impacts patient quality of life and functional ability.
Secondary objectives include:
- Further evaluation of the analgesic efficacy of DFL24412 80 mg-34 mg and DFL24412 40 mg-17 mg in chronic low back pain compared to KLS 80 mg.
- Assessment of the efficacy of DFL24412 compared to KLS on the neuropathic component in chronic low back pain.
- Evaluation of the effect of DFL24412 compared to KLS on quality of life, Patient Global Impression of Change, and work and mental impact.
- Evaluation of the safety of DFL24412 80 mg-34 mg and DFL24412 40 mg-17 mg in chronic low back pain compared to KLS 80 mg.
Participants
The clinical trial focuses on evaluating the efficacy of DFL24412 in individuals with **chronic low back pain**. The study population includes both male and female participants aged between 18 and 65 years. Participants are required to have a diagnosis of chronic low back pain, characterized by pain localized below the costal margin and above the inferior gluteal folds, persisting or recurring for at least three months. The trial does not involve a vulnerable population. Participants must have a normal physical examination, vital signs, clinical laboratory test results, and electrocardiogram (ECG) results, or any abnormalities must be deemed not clinically significant. The trial population was selected based on specific inclusion criteria, including the requirement for stable physical and/or exercise-based therapy for back pain at least three weeks prior to the study. Participants must report at least moderate pain before randomization and, if applicable, adhere to effective contraception methods. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is a **phase 2**, multicenter, randomized, double-blind, active-controlled, parallel-group study designed to assess the analgesic effect and safety of two doses of DFL24412 in patients with **chronic low back pain** compared to Ketoprofen Lysine Salt (KLS). The trial aims to evaluate the efficacy of DFL24412 80 mg-34 mg and DFL24412 40 mg-17 mg administered orally, with the primary endpoint being the change from baseline in average daily low back pain intensity as measured by an 11-point Numeric Rating Scale (NRS) at week 1. Secondary endpoints include changes in neuropathic pain symptom inventory scores, Roland-Morris Disability Questionnaire scores, and other quality of life measures.
The trial is expected to last until October 30, 2025, with participant recruitment having commenced on November 19, 2021. Participants will be involved in the study for a maximum treatment period of 9 weeks. The study includes several key visits: an initial screening visit to confirm eligibility, weekly follow-up visits to monitor progress and collect data, and an end-of-study visit to assess final outcomes and safety. Participants are required to provide written informed consent and meet specific inclusion criteria, such as being aged 18-65 years and having a diagnosis of chronic low back pain persisting for at least 3 months.
Participants may be withdrawn from the study if they experience adverse events, lack of efficacy, or if they do not adhere to the study protocol. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants. The study's design and methodology are structured to provide robust data on the efficacy and safety of the investigational product, contributing valuable insights into the management of chronic low back pain.
Treatment
The clinical trial involves the administration of several treatments to evaluate their efficacy and safety in patients with chronic low back pain. The experimental medication **KLS-GABA 40mg-17mg** is a hard capsule containing **ketoprofen lysine** and **gabapentin**. It is administered orally with a maximum daily dose of 171 mg and a total dose of 513 mg over a treatment period of 9 days. This formulation is designed to provide analgesic and anti-inflammatory effects.
Another experimental medication, **KLS-GABA 80mg-34mg**, also in the form of a hard capsule, contains the same active substances, **ketoprofen lysine** and **gabapentin**. This medication is administered orally with a maximum daily dose of 342 mg and a total dose of 3078 mg over a 9-day treatment period. It serves the same purpose of providing analgesic and anti-inflammatory effects.
The comparator treatment in the study is **OKi 80 mg granulato per soluzione orale**, which contains **ketoprofen lysine** as the active substance. This oral solution is administered with a maximum daily dose of 240 mg and a total dose of 2160 mg over a 9-day treatment period. It functions as an anti-inflammatory agent.
An auxiliary treatment, **TACHIPIRINA 500 mg compresse**, contains **paracetamol** and is administered in tablet form. The maximum daily dose is 3 grams, with a total dose of 147 grams over a 49-day treatment period. This medication is used for its analgesic and antipyretic properties.
All medications are administered orally, and participant compliance is monitored throughout the trial to ensure adherence to the dosing schedules. The trial is designed to assess the analgesic effect and safety of the experimental medications compared to the comparator treatment.
Efficacy
The efficacy of the investigational products in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the change from baseline in average daily low back pain intensity, measured by an 11-point Numeric Rating Scale (NRS) at Week 1. Secondary endpoints include various measures such as the change from baseline in the Neuropathic Pain Symptom Inventory (NPSI) score, Douleur Neuropathique en 4 Questions (DN4) score, and Roland-Morris Disability Questionnaire (RMDQ) total score, all at Week 1. Additionally, the Patient Global Impression of Change (PGI-C) score and changes in the European Quality of Life Questionnaire-5 Dimension-5 Level (EQ-5D-5L) and Work Productivity and Activity Impairment (WPAI) Instrument will be evaluated at Week 1.
Data collection will occur at specified time points, including baseline, Week 1, and a follow-up visit on Day 21. The efficacy parameters will be measured using validated scales and questionnaires, ensuring the reliability and accuracy of the data. The analysis will focus on comparing the efficacy of two doses of DFL24412 against Ketoprofen Lysine Salt (KLS) in patients with chronic low back pain. The trial aims to provide comprehensive insights into the analgesic effects and safety profile of the investigational products.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Provide written informed consent before the initiation of any study-specific procedures
- Must be 18-65 years of age at the time of signing the Informed Consent Form (ICF)
- Have a normal physical examination (except features of CLBP as per IC 4, 5, and 6), vital signs, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal results that are judged not clinically significant by the PI and documented as such in the eCRF
- Diagnosis of chronic low back pain (CLBP, pain localised below the costal margin and above the inferior gluteal folds with no known specific pathology, persisting/recurring for at least 3 months) with no substantial recent change in pain severity or clinical management, with or without lumbosacral radicular pain and/or radiculopathy
- Clinically documented nociceptive and neuropathic components ((‘probable neuropathic pain’ as per International Association for the Study of Pain, IASP)
- Report at least moderate pain (NRS ≥ 4) before randomization
- If undergoing physical and/or exercise-based therapy for back pain, therapy must be stable at least three weeks prior to study and remain the same throughout study
- If a female with childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test; Women of childbearing age and potential must be willing to use highly effective contraception during the study and for 3 months after the last study treatment dose. Male patients and their female partners of childbearing age and potential must be willing to use effective contraception during the study and for 3 months after the last study treatment dose. Highly effective methods of birth control are listed in Appendix 4 of Protocol KLG0121.
- Have a negative COVID-19 antigen rapid test or have received vaccination for COVID-19
Exclusion Criteria
- History of major thoraco-abdominal or low back surgery in the last 3 months
- CLBP due to malignancy, fibromyalgia, ochronosis, recent trauma, infection, juvenile scoliosis or congenital malformation
- Previous diagnosis of psychosis, bipolar disorder, schizoaffective disorder, major depressive disorder or neurological disorder
- CLBP management requiring opioids or surgery and interventional procedures planned in the following 3 months
- Any concomitant use of antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs, muscle relaxants, and/or any other prohibited medication as listed in Appendix 6 of Protocol KLG0121 during the trial or being anticipated by the investigator to be required
- Any concurrent medical condition that, in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient’s well-being
- History of drug and/or alcohol abuse or dependence, excluding nicotine and caffeine
- Have alanine aminotransferase or aspartate aminotransferase higher than 100 International Units per Liter (IU/L) or total bilirubin higher than 1.6 milligram per deciliter (mg/dL)
- Have serum creatinine level higher than 1.6 mg/dL or creatinine clearance < 60, or had renal transplantation or receiving renal dialysis
- Severe or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic diseases, symptomatic peripheral vascular disease, hemorrhagic diathesis, haemolytic anemia, systemic immune-mediated and rheumatologic disorders, or other medical condition or psychiatric conditions that, in the opinion of investigator, would compromise participation or be likely to lead to hospitalization during the course of the study
- History of bronchial asthma, peptic ulcer, gastrointestinal bleeding, ulceration or perforation
- Crohn’s disease or ulcerative colitis
- Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (antiHCV) or human immunodeficiency virus I and II antibodies (anti-HIV I/II)
- History of intolerance or hypersensitivity to: ketoprofen lysine salt or other drugs of the same class, gabapentin, rescue medications, component of the formulation; any history of severe drug allergy or hypersensitivity
- Female patients who meet the following criteria: Pregnant, breast-feeding, and/or planning to become pregnant and/or breast-feed during the study
- Treatment with any investigational product (IP) during the study and within the 3 months (or at least 5 half-lives, whichever is longer) prior to Visit 1
- Be an employee or a relative of an employee of the investigational study center
- Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments
- Unable or unlikely to comply with the study protocol, to fulfill eDiary/ paper Diary and questionnaires appropriately or unsuitable for any other reason, as judged by the PI
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 19 Nov 2021 | 100 |
 Spain | Not Recruiting | 19 Nov 2021 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TACHIPIRINA 500 mg compresse | Other | COMPRESSE | ORAL | 3 | 49 | PRD514384 |
OKi 80 mg granulato per soluzione orale | Comparator | GRANULATO PER SOLUZIONE ORALE | ORAL | 240 | 9 | PRD1874883 |
KLS-GABA 40mg-17mg | Test | CAPSULE, HARD | ORAL | 171 | 9 | PRD8571167 |
KLS-GABA 80mg-34mg | Test | CAPSULE, HARD | ORAL | 342 | 9 | PRD8571171 |