Phase II Randomized, Double-Blind, Dose-Finding Study of Montelukast in Erosive Hand Osteoarthritis Patients
- Trial ID
- 2023-506137-30-00
- Protocol
- FMLD-ARSIDOS-55_FII
- Sponsor
- Farmalider S.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the difference in **pain intensity** of the most affected hand at 8 weeks of treatment with different doses of **Montelukast**, compared to placebo, in patients with **erosive hand osteoarthritis** (EHOA), using the Visual Analogue Scale (VAS). This is clinically relevant as it aims to determine the efficacy of Montelukast in reducing pain, which is a significant symptom impacting the quality of life in patients with EHOA.
Secondary objectives include:
- Evaluating the difference in pain intensity of the most affected hand at 4 weeks of treatment with different doses of Montelukast, compared to placebo, using the VAS.
- Assessing the difference in pain, stiffness, and physical function of the most affected hand at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo, using the AUSCAN questionnaire.
- Evaluating the difference in hand grip strength of the most affected hand at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo, using a dynamometer.
- Determining the proportion of patients using rescue medication at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo.
- Assessing the amount of rescue medication used at 4 and 8 weeks of treatment with different doses of Montelukast, compared to placebo.
- Evaluating the difference in the quality of life of the different treatment groups, compared to placebo, at 4 and 8 weeks, using the EuroQol-5D-5L Questionnaire.
- Assessing the differences in difficulty sleeping due to pain of the most affected hand of the different treatment groups, compared to placebo, at 4 and 8 weeks, using a generic question.
- Evaluating the safety and tolerability of the different doses of Montelukast used in the study, compared with placebo.
Participants
The clinical trial focuses on patients diagnosed with **erosive osteoarthritis of the hands**, specifically targeting individuals with significant clinical activity in the interphalangeal joints. The study population includes both male and female participants aged 18 years and older. The trial does not involve a vulnerable population. Participants were selected based on their ability to provide written informed consent and their willingness to comply with all scheduled visits and procedures. They must exhibit a Visual Analogue Scale (VAS) pain score of 50 mm or higher in the most affected hand at baseline and demonstrate functional impairment, as indicated by a score of 2 or more on a specific question of the AUSCAN Questionnaire. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is a **randomized**, multi-centre, double-blind, phase II study designed to evaluate the efficacy of different doses of **Montelukast** in patients with erosive osteoarthritis of the hands. The primary objective is to assess the difference in pain intensity of the most affected hand at 8 weeks of treatment with Montelukast, compared to placebo, using the Visual Analogue Scale (VAS). The trial involves the administration of Montelukast in hard capsule form, with doses of 5, 10, 15, and 30 mg, and a placebo control. The study is expected to last until March 31, 2024, with recruitment starting on November 15, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), diagnosis of erosive osteoarthritis of the interphalangeal joints, and a VAS pain score of ≥50 mm. Following the screening, participants will be randomized to receive either Montelukast or placebo. The trial includes follow-up visits at 4 and 8 weeks to monitor efficacy and safety endpoints, including pain intensity, hand grip strength, and quality of life assessments. The end-of-study visit will occur at 8 weeks, marking the conclusion of the participant's involvement in the trial.
The expected length of participant involvement is approximately 8 weeks, with conditions for early termination including non-compliance with study procedures or the occurrence of adverse events. Safety endpoints will be assessed through vital signs, physical examinations, and analytical parameters at baseline, 4 weeks, and 8 weeks. The trial aims to provide valuable insights into the optimal dosing of Montelukast for managing pain in patients with erosive hand osteoarthritis.
Treatment
The clinical trial involves the administration of several **experimental medications** containing the active substance **montelukast**, a leukotriene receptor antagonist. The medications are provided in the form of hard capsules and are administered orally. The trial includes four different formulations of montelukast, each with varying dosages. **Montelukast A** is administered at a maximum daily dose of 5 mg, **Montelukast B** at 10 mg, **Montelukast C** at 15 mg, and **Montelukast D** at 30 mg. Each formulation is designed for a maximum treatment period of 2 weeks. The active substance, montelukast, is of chemical origin and is manufactured by FARMALIDER S.A. The dosing schedule is structured to ensure participant compliance, with the frequency of administration being once daily.
In addition to the experimental medications, a **placebo** is utilized as a non-experimental treatment in the study. The placebo is used to provide a control for evaluating the efficacy of the montelukast formulations. The placebo does not contain any active substance and is administered in a manner consistent with the experimental treatments to maintain the double-blind nature of the trial. The placebo is also administered orally, aligning with the administration route of the experimental medications.
Efficacy
The efficacy of Montelukast in patients with erosive hand osteoarthritis (EHOA) will be assessed through a randomized, multi-centre, double-blind, phase II clinical trial. The primary endpoint for evaluating efficacy is the difference in pain intensity of the most affected hand at 8 weeks of treatment, compared to baseline, using the Visual Analogue Scale (VAS). This will be measured for different doses of Montelukast (5, 10, 15, and 30 mg) and compared to a placebo group.
Secondary efficacy endpoints include:
- The pain intensity difference (PID) at 4 weeks, measured through the VAS.
- Changes in the AUSCAN subscales (pain, stiffness, and physical function) scores at 4 and 8 weeks.
- Hand grip strength changes at 4 and 8 weeks, measured using a dynamometer.
- The proportion of patients using rescue medication and the amount used at 4 and 8 weeks.
- Quality of life changes, assessed using the EuroQol-5D-5L questionnaire at 4 and 8 weeks.
- Sleeping difficulty due to hand pain, evaluated with a generic question at 4 and 8 weeks.
Safety endpoints will also be monitored, including vital signs, physical examinations, analytical parameters, and adverse events throughout the study. The trial will involve scheduled assessments at baseline, 4 weeks, and 8 weeks to collect and analyze these parameters, ensuring a comprehensive evaluation of Montelukast's efficacy and safety in treating EHOA.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients who provide written informed consent and are willing to comply with all scheduled visits and procedures required by the study.
- Patients ≥ 18 years at the time of the baseline visit.
- Patients with erosive osteoarthritis of the interphalangeal joints of the hand with significant clinical activity according to Anandarajah criteria.
- Patients with VAS pain of the most affected hand ≥ 50 mm at the baseline visit.
- Patients with repercussion in functionality of the most affected hand evaluated with a score ≥2 in the question number 12 (carrying a full pot with one hand) of the function subscale of the AUSCAN Questionnaire.
Exclusion Criteria
- History of fibromyalgia and/or chronic fatigue syndrome.
- Patient with pathologies that according to medical criteria discourage their participation in the study, such as poorly controlled neuropsychiatrics diseases, severe heart disease, liver failure, kidney failure, active malignancies, poorly controlled endocrine-metabolic diseases, coagulopathies, active gastrointestinal ulceration, active infection, epilepsy, and immunocompromised patients.
- Patient with a history of concurrent rheumatic articular diseases (history and/or current presence of signs) that could lead to a misinterpretation or interfere in the evaluation of efficacy in pain, such as chondrocalcinosis, Paget's disease of the ipsilateral extremity in relation to the affected hand, rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis, acromegaly, hemochromatosis, Wilson's disease, osteochondromatosis, seronegative spondyloarthropathy, mixed connective tissue disease, collagen vascular disease, psoriasis and disease Inflammatory bowel (Crohn's disease or Ulcerative Colitis).
- Pain in another part of the body that could interfere with the evaluation and results of the study according investigator criteria.
- Patient taking corticosteroids (oral or injectable) within 4 weeks prior to the baseline visit, or methotrexate, hydroxychloroquine or SYSADOAs (Slow-Acting Drugs for the Symptomatic Treatment of Osteoarthritis) within 12 weeks prior to the baseline visit.
- Patients who have used intra-articular hyaluronic acid (in the study hand) during the 24 weeks prior to the baseline visit.
- Patient undergoing radioactive synoviorthesis (in the study hand).
- Patient being treated with other disease-modifying anti-rheumatic biological drugs.
- Patient being treated with any other medication contraindicated due to risk of interactions with study medication.
- Patient being treated with NSAIDs* and/or analgesics (except paracetamol) or colchicine within 7 days prior to the baseline visit. The use of paracetamol will be allowed up to 24 hours prior to the start of study treatment. *The sporadic use of Ibuprofen in case of an intercurrent disease other than EHOA will be allowed up to 96 hours prior to the screening visit (visit 0), or, to the visit 1. Maximum daily dose of ibuprofen allowed will be 1200mg.
- Patient with a history of allergy or hypersensitivity to the study medication, rescue medication or any of its excipients.
- Patient intolerant to study medication due to galactose intolerance, lactase insufficiency, or glucose-galactose malabsorption.
- Pregnant or lactating women.
- Women of childbearing age and sexually active (excluded from this definition are women whose date of last menstruation is greater than one year from inclusion in this study and those who have undergone a tubal ligation or hysterectomy), who do not agree to take contraceptive measures during the clinical trial. Contraceptive measures include barrier methods, hormonal contraception, intrauterine device (IUD), or sexual abstinence. The investigator is responsible for determining whether the subject has adequate birth control for study participation.
- Patient currently included in or who have participated in a clinical trial with medicines or health products in the 3 months prior to the baseline visit.
- Patients with scheduled surgery during the clinical trial
- History of drug or alcohol abuse during the 12 months prior to the baseline visit.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 15 Nov 2023 | 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 |
|---|---|---|---|---|---|---|
Montelukast B | Test | HARD CAPSULES | ORAL | 10 | 2 | PRD10555651 |
Montelukast D | Test | HARD CAPSULES | ORAL | 30 | 2 | PRD10555652 |
Placebo | Placebo | N/A | — | — | — | N/A |
Montelukast C | Test | HARD CAPSULES | ORAL | 15 | 2 | PRD9539479 |
Montelukast A | Test | HARD CAPSULES | ORAL | 5 | 2 | PRD10555650 |