Osteoarthritis, Knee
Conditions
Keywords
Injections, Intra-Articular
Brief summary
The purpose of this study is to determine whether intra-articular (knee joint) administration of MEN16132 is effective reducing the pain from knee osteoarthritis.
Detailed description
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.
Interventions
DRUGMEN16132 - 0.125 mg
Intra-articular administration of two low doses of MEN16132 at 2-week interval.
DRUGMEN16132 - 0.25 mg
Intra-articular injection of two intermediate doses of MEN16132 at 2-week interval
DRUGMEN16132 - 0.5 mg
Intra-articular injection of two high doses of MEN16132 at 2-week interval
DRUGPlacebo
Intra-articular injection of 2 doses of Placebo control at 2-week interval
Sponsors
Menarini Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Male or female patients ≥40 years old. * Symptomatic primary knee osteoarthritis (ACR criteria) since ≥6 months prior to screening, Kellgren Lawrence Grade 2 or 3, and representing an indication for intra-articular drug injection. * \>50 mm VAS pain score assigned to the index knee at WOMAC VA 3.1-A1 (pain while walking on a flat surface). * \>125 mm VAS pain score assigned to the index knee at WOMAC VA 3.1 A subscore (total pain). * Pain in the index knee on at least 50% of the days in the month preceding the screening. Main
Exclusion criteria
* Patients with Kellgren & Lawrence Grade I or IV (doubtful or severe) osteoarthritis of the knee. * Knee condition representing an indication for surgery * Patients with Inflammatory or crystal arthropathies, acute fractures, severe loss of bone density, bone necrosis. * Patients with isolated patella-femoral syndrome or chondromalacia. * Patients with OA predominant in the lateral compartment or any significant valgus deformity. * Patients with any other disease or condition interfering with the free use and evaluation of the index knee for the 3 month duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis). * Major injury or surgery to the index knee within the previous 12 months prior to screening. * Severe hip osteoarthritis ipsilateral to index knee. * Any pain \>30 mm VAS that could interfere with the assessment of index knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee). * Any pharmacological or non-pharmacological treatment started or changed during 4 weeks prior to randomisation or likely to be changed during the duration of the study * Use of systemic or topical corticosteroids \>10 mg prednisolone equivalent per day during 30 days prior to randomisation. * Use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics) during 1 or 2 weeks prior to randomisation. * Any intra-articular or local periarticular punction, injection or surgery to the index knee during the 6 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC VA 3.1 A Score (Total Pain) | over the 3 weeks after the first administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC VA 3.1. C Score (Function) | up to 3 months after first dose | 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. |
| Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | up to 3 months after first dose | Osteoarthritis Research Society International (OARSI). Response defined as: * a decrease in WOMAC pain or physical-function score by 50% or more and by 20 or more points on the visual analogue scale * OR if two of the following three findings are recorded: 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. |
| Patient Global Assessment | up to 3 months after first dose | 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. |
| WOMAC VA 3.1.B Score (Knee Stiffness) | up to 3 months after first dose | 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. |
| WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | over the 3 weeks after the first administration | 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. |
| Adverse Event Reports | up to 4 months after screening | Incidence of spontaneously reported adverse events |
| Clinically Significant Abnormal Laboratory Tests | up to 4 months from screening | 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. |
| WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | over the 3 weeks after the first administration | 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. |
Countries
France, Germany, Italy, Spain
Participant flow
Recruitment details
Outpatients were recruited from March 2010 to November 2010 in private practice and hospitals.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose two doses | 83 |
| Mid Dose two doses | 88 |
| High Dose two doses | 84 |
| Single High Dose one dose+placebo | 84 |
| Placebo two doses | 84 |
| Total | 423 |
Baseline characteristics
| Characteristic | Low Dose | Mid Dose | High Dose | Single High Dose | Placebo | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 66.7 years STANDARD_DEVIATION 9 | 65.9 years STANDARD_DEVIATION 9.5 | 65.1 years STANDARD_DEVIATION 9.7 | 65.3 years STANDARD_DEVIATION 8.7 | 65.1 years STANDARD_DEVIATION 8.5 | 65.6 years STANDARD_DEVIATION 9.1 |
| Duration of osteoarthritis symptoms | 9.7 years STANDARD_DEVIATION 9.2 | 8.0 years STANDARD_DEVIATION 6.3 | 7.9 years STANDARD_DEVIATION 6.6 | 8.2 years STANDARD_DEVIATION 8.4 | 6.5 years STANDARD_DEVIATION 6.4 | 8.0 years STANDARD_DEVIATION 7.5 |
| Radiographic Osteoarthritis severity Grade 1 Kellgren-Lawrence scale(doubtful severity) | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Radiographic Osteoarthritis severity Grade 2 Kellgren-Lawrence scale(minimal severity) | 52 participants | 45 participants | 44 participants | 41 participants | 42 participants | 224 participants |
| Radiographic Osteoarthritis severity Grade 3 Kellgren-Lawrence scale(moderate severity) | 31 participants | 43 participants | 40 participants | 42 participants | 42 participants | 198 participants |
| Radiographic Osteoarthritis severity Grade 4 Kellgren-Lawrence scale(severe) | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Radiographic Osteoarthritis severity missing information | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 44 Participants | 46 Participants | 51 Participants | 56 Participants | 55 Participants | 252 Participants |
| Sex: Female, Male Male | 39 Participants | 42 Participants | 33 Participants | 28 Participants | 29 Participants | 171 Participants |
| WOMAC VA 3.1 A score (Total pain) | 288 mm STANDARD_DEVIATION 80 | 282 mm STANDARD_DEVIATION 68 | 293 mm STANDARD_DEVIATION 73 | 283 mm STANDARD_DEVIATION 72 | 284 mm STANDARD_DEVIATION 79 | 286 mm STANDARD_DEVIATION 74 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 83 | 18 / 88 | 21 / 83 | 15 / 83 | 16 / 84 |
| serious Total, serious adverse events | 1 / 83 | 2 / 88 | 3 / 83 | 3 / 83 | 2 / 84 |
Outcome results
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.
Time frame: over the 3 weeks after the first administration
Population: analysis of the intention to treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | WOMAC VA 3.1 A Score (Total Pain) | 1 week post dose 1 | -60 mm | Standard Deviation 84 |
| Low Dose | WOMAC VA 3.1 A Score (Total Pain) | 3 weeks post dose 1 | -103 mm | Standard Deviation 107 |
| Low Dose | WOMAC VA 3.1 A Score (Total Pain) | 2 weeks post dose 1 | -69 mm | Standard Deviation 89 |
| Mid Dose | WOMAC VA 3.1 A Score (Total Pain) | 2 weeks post dose 1 | -65 mm | Standard Deviation 81 |
| Mid Dose | WOMAC VA 3.1 A Score (Total Pain) | 1 week post dose 1 | -58 mm | Standard Deviation 82 |
| Mid Dose | WOMAC VA 3.1 A Score (Total Pain) | 3 weeks post dose 1 | -99 mm | Standard Deviation 86 |
| High Dose | WOMAC VA 3.1 A Score (Total Pain) | 2 weeks post dose 1 | -71 mm | Standard Deviation 102 |
| High Dose | WOMAC VA 3.1 A Score (Total Pain) | 1 week post dose 1 | -52 mm | Standard Deviation 92 |
| High Dose | WOMAC VA 3.1 A Score (Total Pain) | 3 weeks post dose 1 | -99 mm | Standard Deviation 104 |
| Single High Dose | WOMAC VA 3.1 A Score (Total Pain) | 1 week post dose 1 | -67 mm | Standard Deviation 91 |
| Single High Dose | WOMAC VA 3.1 A Score (Total Pain) | 3 weeks post dose 1 | -103 mm | Standard Deviation 99 |
| Single High Dose | WOMAC VA 3.1 A Score (Total Pain) | 2 weeks post dose 1 | -73 mm | Standard Deviation 96 |
| Placebo | WOMAC VA 3.1 A Score (Total Pain) | 2 weeks post dose 1 | -75 mm | Standard Deviation 93 |
| Placebo | WOMAC VA 3.1 A Score (Total Pain) | 1 week post dose 1 | -63 mm | Standard Deviation 103 |
| Placebo | WOMAC VA 3.1 A Score (Total Pain) | 3 weeks post dose 1 | -103 mm | Standard Deviation 112 |
Comparison: Tests of Fixed Effects for the primary efficacy variable including baseline treatment and visit (from Visit 3 to Visit 5) as covariatesp-value: 0.5263ANCOVA
Secondary
Adverse Event Reports
Incidence of spontaneously reported adverse events
Time frame: up to 4 months after screening
Population: The number of patients reflects all patients administered at least one dose of the investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Adverse Event Reports | Nervous system disorders | 6 participants |
| Low Dose | Adverse Event Reports | Musculoskeletal and connective tissue disorders | 6 participants |
| Low Dose | Adverse Event Reports | Investigations | 2 participants |
| Low Dose | Adverse Event Reports | Non-serious adverse events | 31 participants |
| Low Dose | Adverse Event Reports | Metabolism and nutrition disorders | 1 participants |
| Low Dose | Adverse Event Reports | Vascular disorders | 4 participants |
| Low Dose | Adverse Event Reports | Blood / Lymph system | 0 participants |
| Low Dose | Adverse Event Reports | Surgical and medical procedures | 1 participants |
| Low Dose | Adverse Event Reports | Cardiac disorders | 2 participants |
| Low Dose | Adverse Event Reports | Skin and subcutaneous tissue disorders | 1 participants |
| Low Dose | Adverse Event Reports | Eye disorders | 0 participants |
| Low Dose | Adverse Event Reports | Social circumstances | 0 participants |
| Low Dose | Adverse Event Reports | Respiratory, thoracic, and mediastinal disorders | 0 participants |
| Low Dose | Adverse Event Reports | Gastrointestinal disorders | 5 participants |
| Low Dose | Adverse Event Reports | Renal and Urinary disorders | 0 participants |
| Low Dose | Adverse Event Reports | General / administration site conditions | 3 participants |
| Low Dose | Adverse Event Reports | Psychiatric disorders | 1 participants |
| Low Dose | Adverse Event Reports | Infections / infestations | 11 participants |
| Low Dose | Adverse Event Reports | Serious adverse events | 1 participants |
| Low Dose | Adverse Event Reports | Injury / poisoning / procedural complications | 3 participants |
| Mid Dose | Adverse Event Reports | Infections / infestations | 11 participants |
| Mid Dose | Adverse Event Reports | Injury / poisoning / procedural complications | 4 participants |
| Mid Dose | Adverse Event Reports | Serious adverse events | 2 participants |
| Mid Dose | Adverse Event Reports | Musculoskeletal and connective tissue disorders | 11 participants |
| Mid Dose | Adverse Event Reports | Respiratory, thoracic, and mediastinal disorders | 1 participants |
| Mid Dose | Adverse Event Reports | Nervous system disorders | 3 participants |
| Mid Dose | Adverse Event Reports | Investigations | 3 participants |
| Mid Dose | Adverse Event Reports | Eye disorders | 0 participants |
| Mid Dose | Adverse Event Reports | Metabolism and nutrition disorders | 0 participants |
| Mid Dose | Adverse Event Reports | General / administration site conditions | 4 participants |
| Mid Dose | Adverse Event Reports | Vascular disorders | 4 participants |
| Mid Dose | Adverse Event Reports | Surgical and medical procedures | 0 participants |
| Mid Dose | Adverse Event Reports | Renal and Urinary disorders | 0 participants |
| Mid Dose | Adverse Event Reports | Blood / Lymph system | 0 participants |
| Mid Dose | Adverse Event Reports | Non-serious adverse events | 38 participants |
| Mid Dose | Adverse Event Reports | Psychiatric disorders | 0 participants |
| Mid Dose | Adverse Event Reports | Skin and subcutaneous tissue disorders | 0 participants |
| Mid Dose | Adverse Event Reports | Gastrointestinal disorders | 3 participants |
| Mid Dose | Adverse Event Reports | Cardiac disorders | 3 participants |
| Mid Dose | Adverse Event Reports | Social circumstances | 1 participants |
| High Dose | Adverse Event Reports | Surgical and medical procedures | 1 participants |
| High Dose | Adverse Event Reports | Non-serious adverse events | 36 participants |
| High Dose | Adverse Event Reports | Serious adverse events | 3 participants |
| High Dose | Adverse Event Reports | Blood / Lymph system | 0 participants |
| High Dose | Adverse Event Reports | Cardiac disorders | 1 participants |
| High Dose | Adverse Event Reports | Eye disorders | 0 participants |
| High Dose | Adverse Event Reports | General / administration site conditions | 6 participants |
| High Dose | Adverse Event Reports | Infections / infestations | 10 participants |
| High Dose | Adverse Event Reports | Injury / poisoning / procedural complications | 5 participants |
| High Dose | Adverse Event Reports | Investigations | 3 participants |
| High Dose | Adverse Event Reports | Metabolism and nutrition disorders | 0 participants |
| High Dose | Adverse Event Reports | Musculoskeletal and connective tissue disorders | 11 participants |
| High Dose | Adverse Event Reports | Nervous system disorders | 5 participants |
| High Dose | Adverse Event Reports | Psychiatric disorders | 2 participants |
| High Dose | Adverse Event Reports | Renal and Urinary disorders | 0 participants |
| High Dose | Adverse Event Reports | Respiratory, thoracic, and mediastinal disorders | 0 participants |
| High Dose | Adverse Event Reports | Skin and subcutaneous tissue disorders | 1 participants |
| High Dose | Adverse Event Reports | Gastrointestinal disorders | 2 participants |
| High Dose | Adverse Event Reports | Vascular disorders | 2 participants |
| High Dose | Adverse Event Reports | Social circumstances | 0 participants |
| Single High Dose | Adverse Event Reports | Cardiac disorders | 2 participants |
| Single High Dose | Adverse Event Reports | Infections / infestations | 10 participants |
| Single High Dose | Adverse Event Reports | Gastrointestinal disorders | 2 participants |
| Single High Dose | Adverse Event Reports | Skin and subcutaneous tissue disorders | 1 participants |
| Single High Dose | Adverse Event Reports | Social circumstances | 0 participants |
| Single High Dose | Adverse Event Reports | Blood / Lymph system | 1 participants |
| Single High Dose | Adverse Event Reports | General / administration site conditions | 3 participants |
| Single High Dose | Adverse Event Reports | Renal and Urinary disorders | 0 participants |
| Single High Dose | Adverse Event Reports | Surgical and medical procedures | 1 participants |
| Single High Dose | Adverse Event Reports | Vascular disorders | 4 participants |
| Single High Dose | Adverse Event Reports | Eye disorders | 1 participants |
| Single High Dose | Adverse Event Reports | Investigations | 2 participants |
| Single High Dose | Adverse Event Reports | Serious adverse events | 3 participants |
| Single High Dose | Adverse Event Reports | Metabolism and nutrition disorders | 0 participants |
| Single High Dose | Adverse Event Reports | Psychiatric disorders | 0 participants |
| Single High Dose | Adverse Event Reports | Non-serious adverse events | 28 participants |
| Single High Dose | Adverse Event Reports | Injury / poisoning / procedural complications | 2 participants |
| Single High Dose | Adverse Event Reports | Respiratory, thoracic, and mediastinal disorders | 0 participants |
| Single High Dose | Adverse Event Reports | Musculoskeletal and connective tissue disorders | 10 participants |
| Single High Dose | Adverse Event Reports | Nervous system disorders | 3 participants |
| Placebo | Adverse Event Reports | Musculoskeletal and connective tissue disorders | 12 participants |
| Placebo | Adverse Event Reports | Nervous system disorders | 3 participants |
| Placebo | Adverse Event Reports | General / administration site conditions | 3 participants |
| Placebo | Adverse Event Reports | Psychiatric disorders | 0 participants |
| Placebo | Adverse Event Reports | Gastrointestinal disorders | 2 participants |
| Placebo | Adverse Event Reports | Eye disorders | 0 participants |
| Placebo | Adverse Event Reports | Vascular disorders | 2 participants |
| Placebo | Adverse Event Reports | Renal and Urinary disorders | 2 participants |
| Placebo | Adverse Event Reports | Cardiac disorders | 1 participants |
| Placebo | Adverse Event Reports | Respiratory, thoracic, and mediastinal disorders | 0 participants |
| Placebo | Adverse Event Reports | Blood / Lymph system | 0 participants |
| Placebo | Adverse Event Reports | Skin and subcutaneous tissue disorders | 1 participants |
| Placebo | Adverse Event Reports | Serious adverse events | 2 participants |
| Placebo | Adverse Event Reports | Social circumstances | 0 participants |
| Placebo | Adverse Event Reports | Surgical and medical procedures | 1 participants |
| Placebo | Adverse Event Reports | Investigations | 3 participants |
| Placebo | Adverse Event Reports | Metabolism and nutrition disorders | 2 participants |
| Placebo | Adverse Event Reports | Injury / poisoning / procedural complications | 3 participants |
| Placebo | Adverse Event Reports | Non-serious adverse events | 33 participants |
| Placebo | Adverse Event Reports | Infections / infestations | 10 participants |
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.
Time frame: up to 4 months from screening
Population: Percentage of patients with clinically significant abnormal laboratory tests
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood GGT | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Alkaline Phophatase | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Total Bilirubin | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Creatinine | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Glucose | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Potassium | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Sodium | 0 participants |
| Low Dose | Clinically Significant Abnormal Laboratory Tests | Blood Fibrin D dimer | 1 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Total Bilirubin | 0 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Potassium | 0 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood GGT | 0 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Creatinine | 1 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Alkaline Phophatase | 0 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Fibrin D dimer | 0 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Glucose | 0 participants |
| Mid Dose | Clinically Significant Abnormal Laboratory Tests | Blood Sodium | 0 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Sodium | 0 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Fibrin D dimer | 0 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Creatinine | 0 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Potassium | 1 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Total Bilirubin | 1 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Alkaline Phophatase | 1 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood GGT | 1 participants |
| High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Glucose | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Alkaline Phophatase | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Total Bilirubin | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Creatinine | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Glucose | 1 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Potassium | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Fibrin D dimer | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood GGT | 0 participants |
| Single High Dose | Clinically Significant Abnormal Laboratory Tests | Blood Sodium | 0 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Creatinine | 0 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Fibrin D dimer | 0 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Total Bilirubin | 0 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Sodium | 1 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood GGT | 1 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Potassium | 1 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Alkaline Phophatase | 0 participants |
| Placebo | Clinically Significant Abnormal Laboratory Tests | Blood Glucose | 1 participants |
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.
Time frame: up to 3 months after first dose
Population: intention to treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | Patient Global Assessment | Week 1 | -4.2 mm | Standard Deviation 21.8 |
| Low Dose | Patient Global Assessment | Week 2 | -4.7 mm | Standard Deviation 19.6 |
| Low Dose | Patient Global Assessment | Week 3 | -8.4 mm | Standard Deviation 25.3 |
| Low Dose | Patient Global Assessment | Week 13 | -14.8 mm | Standard Deviation 26.4 |
| Mid Dose | Patient Global Assessment | Week 1 | -3.3 mm | Standard Deviation 20.4 |
| Mid Dose | Patient Global Assessment | Week 13 | -7.5 mm | Standard Deviation 22.3 |
| Mid Dose | Patient Global Assessment | Week 2 | -0.4 mm | Standard Deviation 21.4 |
| Mid Dose | Patient Global Assessment | Week 3 | -4.6 mm | Standard Deviation 21.3 |
| High Dose | Patient Global Assessment | Week 13 | -8.8 mm | Standard Deviation 23.6 |
| High Dose | Patient Global Assessment | Week 2 | -0.3 mm | Standard Deviation 20.6 |
| High Dose | Patient Global Assessment | Week 3 | -6.4 mm | Standard Deviation 21.5 |
| High Dose | Patient Global Assessment | Week 1 | 0.9 mm | Standard Deviation 18.5 |
| Single High Dose | Patient Global Assessment | Week 1 | -6.3 mm | Standard Deviation 23.6 |
| Single High Dose | Patient Global Assessment | Week 2 | -7.4 mm | Standard Deviation 21.9 |
| Single High Dose | Patient Global Assessment | Week 13 | -11.4 mm | Standard Deviation 22.9 |
| Single High Dose | Patient Global Assessment | Week 3 | -10.2 mm | Standard Deviation 24.7 |
| Placebo | Patient Global Assessment | Week 13 | -16.3 mm | Standard Deviation 28.8 |
| Placebo | Patient Global Assessment | Week 3 | -11.7 mm | Standard Deviation 24 |
| Placebo | Patient Global Assessment | Week 2 | -9.0 mm | Standard Deviation 24.6 |
| Placebo | Patient Global Assessment | Week 1 | -7.8 mm | Standard Deviation 22.2 |
Secondary
Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria
Osteoarthritis Research Society International (OARSI). Response defined as: * a decrease in WOMAC pain or physical-function score by 50% or more and by 20 or more points on the visual analogue scale * OR if two of the following three findings are recorded: 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.
Time frame: up to 3 months after first dose
Population: intention to treat (ITT) population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 1 | 44.6 percentage of patients |
| Low Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 2 | 46.3 percentage of patients |
| Low Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 3 | 61.8 percentage of patients |
| Low Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 13 | 64.2 percentage of patients |
| Mid Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 1 | 35.6 percentage of patients |
| Mid Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 13 | 66.7 percentage of patients |
| Mid Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 2 | 36.0 percentage of patients |
| Mid Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 3 | 67.5 percentage of patients |
| High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 13 | 59.8 percentage of patients |
| High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 2 | 37.0 percentage of patients |
| High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 3 | 54.4 percentage of patients |
| High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 1 | 36.6 percentage of patients |
| Single High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 1 | 41.5 percentage of patients |
| Single High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 2 | 47.6 percentage of patients |
| Single High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 13 | 64.6 percentage of patients |
| Single High Dose | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 3 | 57.3 percentage of patients |
| Placebo | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 13 | 53.6 percentage of patients |
| Placebo | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 3 | 57.7 percentage of patients |
| Placebo | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 2 | 53.8 percentage of patients |
| Placebo | Percentage of Treatment Responders According to OMERACT-OARSI Responder Criteria | Week 1 | 44.4 percentage of patients |
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.
Time frame: over the 3 weeks after the first administration
Population: Population of Over Weight patients (BMI \>25)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 1 week post dose 1 | -76.5 mm | Standard Deviation 81.73 |
| Low Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 3 weeks post dose 1 | -103.4 mm | Standard Deviation 95.6 |
| Low Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 2 weeks post dose 1 | -88.2 mm | Standard Deviation 83.18 |
| Mid Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 2 weeks post dose 1 | -78.2 mm | Standard Deviation 75.67 |
| Mid Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 1 week post dose 1 | -62.9 mm | Standard Deviation 81.14 |
| Mid Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 3 weeks post dose 1 | -122.1 mm | Standard Deviation 69.96 |
| High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 2 weeks post dose 1 | -81.5 mm | Standard Deviation 105.08 |
| High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 1 week post dose 1 | -56.4 mm | Standard Deviation 88.08 |
| High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 3 weeks post dose 1 | -114.1 mm | Standard Deviation 106 |
| Single High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 1 week post dose 1 | -67.4 mm | Standard Deviation 86.99 |
| Single High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 3 weeks post dose 1 | -99.6 mm | Standard Deviation 83.74 |
| Single High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 2 weeks post dose 1 | -81.6 mm | Standard Deviation 90.11 |
| Placebo | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 2 weeks post dose 1 | -83.9 mm | Standard Deviation 72.71 |
| Placebo | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 1 week post dose 1 | -58.0 mm | Standard Deviation 70.92 |
| Placebo | WOMAC VA 3.1A - Total Pain Score by Body Mass Index -[BMI > 25] | 3 weeks post dose 1 | -103.3 mm | Standard Deviation 85.26 |
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.
Time frame: over the 3 weeks after the first administration
Population: Population of Normal Weight patients (BMI \<=25)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 1 week post dose 1 | -11.4 mm | Standard Deviation 53.91 |
| Low Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 3 weeks post dose 1 | -22.4 mm | Standard Deviation 100.02 |
| Low Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 2 weeks post dose 1 | 9.2 mm | Standard Deviation 97.88 |
| Mid Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 2 weeks post dose 1 | -90.7 mm | Standard Deviation 70.94 |
| Mid Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 1 week post dose 1 | -72.4 mm | Standard Deviation 55.78 |
| Mid Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 3 weeks post dose 1 | -110.7 mm | Standard Deviation 80.72 |
| High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 2 weeks post dose 1 | -99.2 mm | Standard Deviation 39.89 |
| High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 1 week post dose 1 | -109.0 mm | Standard Deviation 91.97 |
| High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 3 weeks post dose 1 | -107.8 mm | Standard Deviation 46.16 |
| Single High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 1 week post dose 1 | -109.0 mm | Standard Deviation 86.66 |
| Single High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 3 weeks post dose 1 | -112.9 mm | Standard Deviation 93.52 |
| Single High Dose | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 2 weeks post dose 1 | -63.8 mm | Standard Deviation 90.05 |
| Placebo | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 2 weeks post dose 1 | -31.2 mm | Standard Deviation 71.8 |
| Placebo | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 1 week post dose 1 | 2.7 mm | Standard Deviation 75.21 |
| Placebo | WOMAC VA 3.1A - Total Pain Score by Body Mass Index [BMI <= 25] | 3 weeks post dose 1 | -62.3 mm | Standard Deviation 83.43 |
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.
Time frame: up to 3 months after first dose
Population: Intention to Treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Baseline | 105.7 mm | Standard Deviation 47.36 |
| Low Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Week 13 | 61.5 mm | Standard Deviation 52.2 |
| Mid Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Baseline | 101.8 mm | Standard Deviation 39.7 |
| Mid Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Week 13 | 66.1 mm | Standard Deviation 47.4 |
| High Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Baseline | 109.4 mm | Standard Deviation 46.21 |
| High Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Week 13 | 64.5 mm | Standard Deviation 50.1 |
| Single High Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Week 13 | 66.2 mm | Standard Deviation 49.3 |
| Single High Dose | WOMAC VA 3.1.B Score (Knee Stiffness) | Baseline | 107.3 mm | Standard Deviation 43.3 |
| Placebo | WOMAC VA 3.1.B Score (Knee Stiffness) | Baseline | 108.7 mm | Standard Deviation 47.67 |
| Placebo | WOMAC VA 3.1.B Score (Knee Stiffness) | Week 13 | 63.4 mm | Standard Deviation 51.3 |
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.
Time frame: up to 3 months after first dose
Population: Intention to Treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | WOMAC VA 3.1. C Score (Function) | Baseline | 928.7 mm | Standard Deviation 336.2 |
| Low Dose | WOMAC VA 3.1. C Score (Function) | Week 13 | 537.5 mm | Standard Deviation 415.9 |
| Mid Dose | WOMAC VA 3.1. C Score (Function) | Baseline | 915.5 mm | Standard Deviation 285.2 |
| Mid Dose | WOMAC VA 3.1. C Score (Function) | Week 13 | 598.0 mm | Standard Deviation 396.9 |
| High Dose | WOMAC VA 3.1. C Score (Function) | Baseline | 906.7 mm | Standard Deviation 318.19 |
| High Dose | WOMAC VA 3.1. C Score (Function) | Week 13 | 574.6 mm | Standard Deviation 407 |
| Single High Dose | WOMAC VA 3.1. C Score (Function) | Week 13 | 594.8 mm | Standard Deviation 444.3 |
| Single High Dose | WOMAC VA 3.1. C Score (Function) | Baseline | 938.7 mm | Standard Deviation 300.63 |
| Placebo | WOMAC VA 3.1. C Score (Function) | Baseline | 936.5 mm | Standard Deviation 343.8 |
| Placebo | WOMAC VA 3.1. C Score (Function) | Week 13 | 557.6 mm | Standard Deviation 389 |