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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-014918-99 | EudraCT Number |
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The purpose of this study is to determine whether intra-articular (knee joint) administration of MEN16132 is effective reducing the pain from knee osteoarthritis.
MEN16132 is a non-peptide bradykinin B2-receptor antagonist showing analgesic and anti-inflammatory activity in nonclinical osteoarthritis models. This study is being conducted as a dose finding study to determine the safety and efficacy of MEN16132, given as three doses/four treatment regimens in comparison to placebo, as well the time to onset and duration of effect.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Double dose MEN16132 0.125 mg | Experimental | Intra-articular administration of two 0.125 mg doses of MEN16132 at 2-week interval. |
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| Double dose MEN16132 0.25 mg | Experimental | Intra-articular administration of two 0.25 mg doses of MEN16132 at 2-week interval. |
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| Double dose MEN16132 0.5 mg | Experimental | Intra-articular administration of two 0.5 mg doses of MEN16132 at 2-week interval. |
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| Single dose MEN16132 0.5 mg | Experimental | Intra-articular administration of one 0.5 mg dose of MEN16132 followed by one intra-articular injection of placebo at 2-week interval. |
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| Placebo | Placebo Comparator | Intra-articular administration of two doses of Placebo at 2-week interval. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEN16132 - 0.125 mg | Drug | Intra-articular administration of two low doses of MEN16132 at 2-week interval. |
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| Measure | Description | Time Frame |
|---|---|---|
| WOMAC VA 3.1 A Score (Total Pain) | Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The WOMAC VA 3.1 A score (total pain , range 0-500 mm) is the sum of VAS scores (0-100 mm) attributed by the patient to each of the 5 questions referring to osteoarthritic pain experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 A score, the higher is the intensity of pain symptoms (0 = no pain ; 500 = extreme pain). A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. The change from baseline was assessed along 3 weeks after first drug administrations. | over the 3 weeks after the first administration |
| Measure | Description | Time Frame |
|---|---|---|
| WOMAC VA 3.1.B Score (Knee Stiffness) | WOMAC VA 3.1.B score(range 0-200) is the sum of VAS scores (0-100 mm)attributed by the patient to each of the 2 questions referring to joint stiffness experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 B score, the higher is joint stiffness (0 = no stiffness ; 200 = extreme stiffness). A decrease of the WOMAC VA 3.1 B score following treatment administration indicates a reduction of joint stiffness. The change at Week 13 from baseline is reported. |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karel Pavelka, Prof MD | Institute of Rheumatology, Charles University Prague | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Régional - Hôpital Porte Madeleine | Orléans | 45000 | France | |||
| Hôtel Dieu - GHU Ouest |
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Outpatients were recruited from March 2010 to November 2010 in private practice and hospitals.
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose | two intra-articular fasitibant doses; 0.125 mg each |
| FG001 | Mid Dose | two intra-articular fasitibant doses; 0.25 mg each |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| MEN16132 - 0.25 mg | Drug | Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval |
|
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| MEN16132 - 0.5 mg | Drug | Intra-articular injection of two high doses of MEN16132 at 2-week interval |
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| MEN16132 - 0.5 mg | Drug | Single intra-articular injection of one high dose of MEN16132, followed by one dose of placebo at 2-week interval |
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| Placebo | Drug | Intra-articular injection of 2 doses of Placebo control at 2-week interval |
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| up to 3 months after first dose |
| WOMAC VA 3.1. C Score (Function) | Knee function evaluated by WOMAC VA 3.1 C score (range 0-1700) is the sum of VAS scores (range 0-100 mm) attributed by the patient to each of 17 questions referring to difficulty in performing daily activities experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 C score, the higher is functional impairment in daily activities (0 = no difficulty ; 1700 = extreme difficulty). A decrease of the WOMAC VA 3.1 C score following treatment administration indicates an improvement in performing daily activities. WOMAC VA 3.1.C scores at baseline and at Week 13 are reported. | up to 3 months after first dose |
| Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Osteoarthritis Research Society International (OARSI). Response defined as:
a decrease in the WOMAC pain score by 20% or more and by 10 or more points on the visual analogue scale; a decrease in the WOMAC physical-function score by 20% or more and by 10 or more points on the scale; an improvement in the score on the patient's global assessment by 20% or more and by 10 or more points on the scale. | up to 3 months after first dose |
| Patient Global Assessment | Patient global assessment evaluated using a VAS scale score attributed by the patient (range 0-100 mm). Efficacy assessed as change at each time-point post-dosing (week 1, 2 ,3, 13) versus baseline (week 0). A decrease of patient global assessment score indicates an improvement of osteoarthritis symptoms. | up to 3 months after first dose |
| WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | Analysis in normal-weight population (BMI <= 25) of the WOMAC VA 3.1A score (range 0-500 mm) is reported. A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. | over the 3 weeks after the first administration |
| WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | Analysis in over-weight population (BMI > 25) of the WOMAC VA 3.1A score (range 0-500 mm) is reported. A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. | over the 3 weeks after the first administration |
| Adverse Event Reports | Incidence of spontaneously reported adverse events | up to 4 months after screening |
| Clinically Significant Abnormal Laboratory Tests | Percentage of patients with Abnormal Laboratory Tests judged Clinically Significant by Investigators. The following hematochemical and urinary parameters were analysed: Red Blood Cells Count, Haematocrit, Haemoglobin, Platelets, MCV, MCH, MCHC, White Blood Cells, Sodium, Chloride, Potassium, Total calcium, AST (SGOT), ALT (SGPT), GGT, Alkaline phosphatase, Total Bilirubin, Direct Bilirubin, Creatinine, BUN, CPK, LDH, Glucose, Total proteins, Albumin. | up to 4 months from screening |
| Paris |
| 75181 |
| France |
| Department of Rheumatology, Purpan University Hospital | Toulouse | 31300 | France |
| Rheumatologie/Immunologie - Rheumazentrum, Krankenhaus Doberan | Bad Doberan | 18209 | Germany |
| Klinik für Rheumatologie und Klinische Immunologie, Charité - Campus Charité Mitte | Berlin | 10117 | Germany |
| Orthopädische Praxis Dr. Wagenitz | Berlin | 12247 | Germany |
| ClinPharm International, Prüfzentrum Bochum | Bochum | 44787 | Germany |
| ClinPharm International, Prüfzentrum Dresden | Dresden | 01067 | Germany |
| Medizinische Klinik 3, Universität Erlangen-Nürnberg | Erlangen | 91054 | Germany |
| ClinPharm Prüfzentrum Frankfurt / aM | Frankfurt | 60596 | Germany |
| ClinPharm Prüfzentrum Görlitz | Görlitz | 02826 | Germany |
| Clinical Research Hamburg | Hamburg | 22143 | Germany |
| Orthopädie Zentrum Altona | Hamburg | 22767 | Germany |
| ClinPharm International, Prüfzentrum Leipzig | Leipzig | 04103 | Germany |
| ClinPharm Prüfzentrum Magdeburg | Magdeburg | 39104 | Germany |
| Servizio di Reumatologia, Ospedale Privato Accreditato Nigrisoli | Bologna | 40138 | Italy |
| Dipartimento di Biomedicina - SOD Reumatologia - Azienda Ospedaliera Universitaria Careggi | Florence | 50139 | Italy |
| Dipartimento di Medicina Interna Azienda Ospedaliero Universitaria Pisana-Stabilimento di Santa Chiara Pisa | Pisa | 56126 | Italy |
| Istituto di Reumatologia, "Policlinico Le Scotte" Università degli Studi di Siena | Siena | 53100 | Italy |
| Servicio de Reumatologia, Hospital de Basurto | Bilbao | 48013 | Spain |
| Servicio de Reumatologia, Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Servicio de Reumatologia, Corporacio Sanitaria Parc Tauli, Hospital de Sabadell | Sabadell | 08208 | Spain |
| Servicio de Reumatologia, Hospital Universitario Virgen Macarena | Seville | 41009 | Spain |
| FG002 | High Dose | two intra-articular fasitibant doses; 0.5 mg each |
| FG003 | Single High Dose | one intra-articular fasitibant dose 0.5 mg +placebo |
| FG004 | Placebo | two intra-articular placebo doses |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose | two doses |
| BG001 | Mid Dose | two doses |
| BG002 | High Dose | two doses |
| BG003 | Single High Dose | one dose+placebo |
| BG004 | Placebo | two doses |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Duration of osteoarthritis symptoms | Mean | Standard Deviation | years |
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| Radiographic Osteoarthritis severity | Based on Kellgren & Lawrence radiologic scale criteria (Grade 1 to 4):
| Number | participants |
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| WOMAC VA 3.1 A score (Total pain) | Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The WOMAC VA 3.1 A score (total pain, range 0-500 mm) is the sum of VAS subscores (0-100 mm) attributed by the patient to each of the 5 questions referring to osteoarthritic pain experienced during the preceding 48 hours (pain domain). The higher is the WOMAC VA 3.1 A score, the higher is the intensity of pain symptoms (0 = no pain ; 500 = extreme pain). A decrease of the WOMAC VA 3.1 A score following tratment administration indicates a reduction of pain symptom. | Mean | Standard Deviation | mm |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | WOMAC VA 3.1 A Score (Total Pain) | Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The WOMAC VA 3.1 A score (total pain , range 0-500 mm) is the sum of VAS scores (0-100 mm) attributed by the patient to each of the 5 questions referring to osteoarthritic pain experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 A score, the higher is the intensity of pain symptoms (0 = no pain ; 500 = extreme pain). A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. The change from baseline was assessed along 3 weeks after first drug administrations. | analysis of the intention to treat (ITT) population | Posted | Mean | Standard Deviation | mm | over the 3 weeks after the first administration |
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| Secondary | WOMAC VA 3.1.B Score (Knee Stiffness) | WOMAC VA 3.1.B score(range 0-200) is the sum of VAS scores (0-100 mm)attributed by the patient to each of the 2 questions referring to joint stiffness experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 B score, the higher is joint stiffness (0 = no stiffness ; 200 = extreme stiffness). A decrease of the WOMAC VA 3.1 B score following treatment administration indicates a reduction of joint stiffness. The change at Week 13 from baseline is reported. | Intention to Treat (ITT) population | Posted | Mean | Standard Deviation | mm | up to 3 months after first dose |
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| Secondary | WOMAC VA 3.1. C Score (Function) | Knee function evaluated by WOMAC VA 3.1 C score (range 0-1700) is the sum of VAS scores (range 0-100 mm) attributed by the patient to each of 17 questions referring to difficulty in performing daily activities experienced during the preceding 48 hours. The higher is the WOMAC VA 3.1 C score, the higher is functional impairment in daily activities (0 = no difficulty ; 1700 = extreme difficulty). A decrease of the WOMAC VA 3.1 C score following treatment administration indicates an improvement in performing daily activities. WOMAC VA 3.1.C scores at baseline and at Week 13 are reported. | Intention to Treat (ITT) population | Posted | Mean | Standard Deviation | mm | up to 3 months after first dose |
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| Secondary | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Osteoarthritis Research Society International (OARSI). Response defined as:
a decrease in the WOMAC pain score by 20% or more and by 10 or more points on the visual analogue scale; a decrease in the WOMAC physical-function score by 20% or more and by 10 or more points on the scale; an improvement in the score on the patient's global assessment by 20% or more and by 10 or more points on the scale. | intention to treat (ITT) population | Posted | Number | percentage of patients | up to 3 months after first dose |
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| Secondary | Patient Global Assessment | Patient global assessment evaluated using a VAS scale score attributed by the patient (range 0-100 mm). Efficacy assessed as change at each time-point post-dosing (week 1, 2 ,3, 13) versus baseline (week 0). A decrease of patient global assessment score indicates an improvement of osteoarthritis symptoms. | intention to treat (ITT) population | Posted | Mean | Standard Deviation | mm | up to 3 months after first dose |
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| Secondary | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | Analysis in normal-weight population (BMI <= 25) of the WOMAC VA 3.1A score (range 0-500 mm) is reported. A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. | Population of Normal Weight patients (BMI <=25) | Posted | Mean | Standard Deviation | mm | over the 3 weeks after the first administration |
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| Secondary | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | Analysis in over-weight population (BMI > 25) of the WOMAC VA 3.1A score (range 0-500 mm) is reported. A decrease of the WOMAC VA 3.1 A score following treatment administration indicates a reduction of pain symptom. | Population of Over Weight patients (BMI >25) | Posted | Mean | Standard Deviation | mm | over the 3 weeks after the first administration |
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| Secondary | Adverse Event Reports | Incidence of spontaneously reported adverse events | The number of patients reflects all patients administered at least one dose of the investigational product. | Posted | Number | participants | up to 4 months after screening |
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| Secondary | Clinically Significant Abnormal Laboratory Tests | Percentage of patients with Abnormal Laboratory Tests judged Clinically Significant by Investigators. The following hematochemical and urinary parameters were analysed: Red Blood Cells Count, Haematocrit, Haemoglobin, Platelets, MCV, MCH, MCHC, White Blood Cells, Sodium, Chloride, Potassium, Total calcium, AST (SGOT), ALT (SGPT), GGT, Alkaline phosphatase, Total Bilirubin, Direct Bilirubin, Creatinine, BUN, CPK, LDH, Glucose, Total proteins, Albumin. | Percentage of patients with clinically significant abnormal laboratory tests | Posted | Number | participants | up to 4 months from screening |
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Four months of safety observation
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low Dose | two doses | 1 | 83 | 17 | 83 | ||
| EG001 | Mid Dose | two doses | 2 | 88 | 18 | 88 | ||
| EG002 | High Dose | two doses | 3 | 83 | 21 | 83 | ||
| EG003 | Single High Dose | one dose+placebo | 3 | 83 | 15 | 83 | ||
| EG004 | Placebo | two doses | 2 | 84 | 16 | 84 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
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| Supraventricular-tachycardia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 10.0 | Systematic Assessment |
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| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Guillain Barré syndrome | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Uretric stenosis | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
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| Ureterocele | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
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| Knee operation | Surgical and medical procedures | MedDRA 10.0 | Systematic Assessment |
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| Prostatectomy | Surgical and medical procedures | MedDRA 10.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA 10.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 10.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Research Director | Menarini-Ricerche | +39-055-56809990 |
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C506838 | (4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium |
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| Male |
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| Grade 2 Kellgren-Lawrence scale(minimal severity) |
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| Grade 3 Kellgren-Lawrence scale(moderate severity) |
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| Grade 4 Kellgren-Lawrence scale(severe) |
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| missing information |
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| 2 weeks post dose 1 |
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| 3 weeks post dose 1 |
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two doses |
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| OG004 | Placebo | two doses |
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| OG004 | Placebo | two doses |
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| Placebo |
two doses |
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