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MOZArT: Study of Intra-articular Injections vs Placebo in Patients With Pain From Osteoarthritis of the Knee

Sponsor
Biologische Heilmittel Heel GmbH (Industry)
Overall Status
Completed
CT.gov ID
NCT01887678
Collaborator
(none)
287
Enrollment
30
Locations
2
Arms
7
Duration (Months)
9.6
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to evaluate the effectiveness and safety of a combined Traumeel® / Zeel® injection against placebo (saline) in patients with moderate-to-severe pain associated with osteoarthritis of the knee.

Condition or Disease Intervention/Treatment Phase
  • Drug: Traumeel® / Zeel® Injectable Solution
  • Drug: Placebo
 Phase 3

Detailed Description

The primary objective is to demonstrate the superiority of Traumeel® and Zeel® co-administered intra-articular (IA) injections vs placebo IA injections on the change in knee pain in patients with moderate to severe knee pain associated with osteoarthritis.

The secondary objectives are to evaluate reduction of pain and stiffness and change in physical function.

Safety is evaluated by the incidence of treatment emergent adverse events during the treatment period and follow up period for all randomized patients.

Study Design

Study Type:
Interventional
Actual Enrollment :
287 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Multi-center Double-blind Randomized Controlled Trial to Evaluate Effectiveness and Safety of Co-administered Traumeel® / Zeel® Intra-articular Injections vs Placebo in Patients With Moderate-to-Severe Pain With Osteoarthritis of the Knee
Study Start Date :
Jun 1, 2013
Actual Primary Completion Date :
Jan 1, 2014
Actual Study Completion Date :
Jan 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Traumeel® / Zeel® Injectable Solution

Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one intra articular (IA) injection) on treatment days 1, 8 and 15.

Drug: Traumeel® / Zeel® Injectable Solution
Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one IA injection) on treatment days 1, 8 and 15.
Other Names:
  • Traumeel
  • Zeel

    		•
    Placebo Comparator: Placebo injectable solution

    Injection volume of placebo is 4.2 mL as well (taken from the 10.0 mL vial by unblinded staff member, rest to be kept for drug accountability)

    Drug: Placebo
    Placebo is an injection of Saline
    Other Names:
  • Saline

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Knee Pain as Measured by the WOMAC Osteoarthritis (OA) Index Pain Subscale (Section A, Items #1-5) Measured by 100 mm VAS [from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)]

      Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess pain, scores from WOMAC Section A, items 1 to 5 are averaged to yield the Pain Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. A two-sided test of equality of the study drug (Traumeel®-Zeel®) and Placebo at level 0.05 was computed using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and the corresponding Baseline value of the primary efficacy variable as a covariate. The test decision was based on the (two-sided) p-value for the corresponding test of no treatment difference.

    Secondary Outcome Measures

    1. Pain Subscore (WOMAC Section A, Items #1-5) Measured by 100 mm VAS [from Baseline to post-Baseline visits except End of Study Visit (up to day 105)]

      Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess pain, scores from WOMAC Section A, items 1 to 5 are averaged to yield the Pain Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in pain subscore were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.

    2. Stiffness Subscore (WOMAC Section B, Items #6-7) Measured by 100 mm VAS [from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)]

      Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess stiffness, scores from WOMAC Section B, items 6 to 7 are averaged to yield the Stiffness Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in stiffness score were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.

    3. Physical Function Bubscore (WOMAC Section C, Items #8-24) Recorded on 100 mm VAS [from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)]

      Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess physical function, scores from WOMAC Section C, items 8 to 24 are averaged to yield the Physical Function Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in Physical Function subscore were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.

    4. Total WOMAC Score (All Subscales) Recorded on 100 mm VAS [from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)]

      Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. A total WOMAC score was computed by averaging all 24 possible responses. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in total WOMAC score were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.

    5. Patient Global Assessment (PGA) [from Baseline (Day 1, predose)]

      Patients made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".

    6. Patient Global Assessment (PGA) [End of Study Visit (up to Day 119)]

      Patients made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".

    7. Physician Global Assessment (PhGA) [Baseline (Day 1, predose)]

      Study Physicians made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".

    8. Physician Global Assessment (PhGA) [End of Study Visit (up to Day 119)]

      Study Physicians made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".

    9. Pain Immediately Following the 50-foot Walk (100 mm VAS) [Baseline (Day 1, predose) to post-Baseline visits (up to day 119)]

      Changes of the target (treated) knee pain following a 50 feet walk self-assessed by the patients on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'.

    10. Time to Walking (50-foot Walk Test) [Baseline (Day 1, predose) to post-Baseline visits (up to day 119)]

      Changes in time to walk 50 feet (seconds)

    11. Time to 50% Pain Relief (Study Population Measure Statistically Derived) [Statistically derived]

      Changes of the target (treated) knee pain following a 50 feet walk self-assessed by the patients on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. The time to 50% pain relief were statistical exercises and were analyzed for each individual patient from their self-assessment.

    12. Patients Achieving 100% Pain Relief [Statistically derived]

      Changes of the target (treated) knee pain following a 50 feet walk self-assessed by the patients on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. The time to 100% pain relief were statistical exercises and were analyzed for each individual patient from their self-assessment, however, the prevalence of 100% pain relief did not support an estimate for the median time. The number of patients who reached 100% pain relief is reported and the log rank test for difference in time to 100% pain relief was calculated for each injection.

    13. Time to and Use of Rescue Medication (Acetaminophen up to 3000 mg Per Day for Breakthrough Pain) (Study Population Measure Statistically Derived) - Patients Use [Statistically derived]

      Time to and use of rescue medication (acetaminophen up to 3000 mg per day for breakthrough pain) as reported by the patients. Patients who used any rescue medication during the study.

    14. Time to and Use of Rescue Medication (Acetaminophen up to 3000 mg Per Day for Breakthrough Pain) (Study Population Measure Statistically Derived). Tablets Taken. [Statistically derived]

      Time to and use of rescue medication (acetaminophen up to 3000 mg per day for breakthrough pain) (study population measure statistically derived). Total number of tablets taken as reported by patient.

    Other Outcome Measures

    1. Serious Adverse Events [Start of Lead-In period until individual study end, up to 16 weeks.]

      Total number of patients affected.

    2. Each Adverse Event (AE) [Starting at Visit 2/ Start of Lead-In period (Day 7 up to day 119)]

      Total number of patients affected.

    3. Incidence of Treatment Emergent Adverse Events (TEAEs) [during the treatment period and follow up period (Days 11 to 119)]

      Total number of patients affected.

    4. Proportion of Patients Who Discontinued Due to an AE [All visits (Days 1 up to 119)]

      Total number of patients affected.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria (Screening Visit 1):

    1. Osteoarthritis (OA) of the knee by American College of Rheumatology criteria

    2. Men or women between 45-80 years of age.

    3. Have documented diagnosis of primary OA of the target knee based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment of the target knee confirmed by standard post-anterior weightbearing X-ray of the knee in full extension taken </= 6 months prior to Visit 1.

    4. Currently taking an Nonsteroidal anti-inflammatory drug (NSAID), or acetaminophen on a regular basis (4-7 days/ week) over last 2 weeks prior to Visit 1 and has experienced amelioration of pain on these medications.

    5. Must have a 50-foot walk test pain score of less than 40 mm on a 100 mm VAS in the target knee at screening

    6. Pain in the non-target (contralateral) knee must not be greater than 30 mm on a 100 mm VAS on 50-foot walk test, and the target knee must be more symptomatic.

    7. Willingness to stop all OA treatments.

    8. Fully informed of the risks of entering the study and willing to provide written consent to enter the study.

    9. Able to understand and be willing to comply with all study requirements, particularly the weekly injection regimen for administration of study drug.

    10. Primary complaint is pain immediately following an unassisted 50-foot walk. They must show:

    11. moderate to severe pain score in the target knee as demonstrated by 40 - 90 mm recorded on a 100 mm VAS, and

    12. 20 mm increase in pain from their screening visit pain score (a "flare")

    13. pain in the non-target (contralateral) knee must </= 30 mm on a 100 mm VAS

    Exclusion Criteria:

    1. Known hypersensitivity or allergy to any of the components of Traumeel or Zeel

    2. Known hypersensitivity or allergy to acetaminophen.

    3. Has body mass index (BMI) >38 kg/m2.

    4. Avoidance of, or aversion to, nonprescription medications.

    5. Clinical symptoms of meniscal instability or significant valgus/ varus that requires corrective osteotomy

    6. Any major injury or surgery to the target knee in the prior 12 months.

    7. One or a combination of the following co-morbidities:

    8. other inflammatory arthropathies, gout or pseudogout within previous 6 months

    9. avascular necrosis

    10. severe bone or joint deformity in target knee

    11. osteonecrosis of either knee

    12. fibromyalgia

    13. pes anserine bursitis

    14. lumbar radiculopathy with referred pain to either knee

    15. neurogenic or vascular claudication

    16. significant anterior knee pain due to diagnosed isolated patella-femoral syndrome in the target knee

    17. target knee joint infection or skin disorder/infection to the area surrounding the knee within previous 6 months

    18. current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin)

    19. Participated in any experimental drug or device study within the prior one (1) month and/or IA injections six (6) months.

    20. Referred pain from other joints

    21. Significantly debilitating concurrent infection(s)

    22. Significant ligamentous instability

    23. Any prior viscosupplementation therapy (in target knee) within 6 months prior to Screening

    24. Systemic or IA injection of corticosteroids in any joint within 3 months of enrollment

    25. Therapy with oral hyaluronic acid products, and/or oral pharmaceutical products containing glucosamine and/or chondroitin sulphate and/or diacerein

    26. Therapy with opioids within the last 90 days including intra-dermal delivery systems (patches)

    27. Therapy with autologous stem cells

    28. Therapy with coumarins such as warfarin, Coumadin; heparin and derivative substances including low molecular weight heparin, synthetic pentasaccharide inhibitors of factor Xa such as fondaparinux and idraparinux; direct factor Xa inhibitors such as rivaroxaban and apixaban; direct thrombin inhibitors such as hirudin, lepirudin, bivalirudin, argatroban and dabigatran.

    29. Concomitant inflammatory or other rheumatologic, neurological or cardiovascular diseases which could affect the evaluation of knee pain

    30. Ongoing litigation for workers compensation for musculoskeletal injuries or disorders

    31. Use of alcohol of more than 4 drinks per day

    32. Clinically important axial deviation (varus, valgus) greater than 15 degrees

    33. Concomitant severe OA of the hip or other joints, which might interfere with the assessments required by the study

    34. Painful knee conditions other than OA (e.g., Paget's disease)

    35. Hemiparesis of lower limbs

    36. Significant planned surgery to lower limbs, which might interfere with the patient's ability to comply with study requirements

    37. Presence of serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular, neurological disease that might interfere with the outcome of the study or the patient's ability to comply with study requirements

    38. Presence of infections and/or skin diseases in the area of the injection site such as psoriasis

    39. Females who are pregnant or breast-feeding or not using recognized effective contraceptive measures. Females of childbearing potential (including those less than one year post-menopausal) must agree to maintain reliable birth control throughout the study.

    40. Clinically significant abnormal laboratory values.

    41. Patients who are likely to be non-compliant or uncooperative during the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Research Advantage - Arizona II Phoenix Arizona United States 85050
    2 Tucson Orthopaedic Institute Tucson Arizona United States 85712
    3 Universal BioPharma Research Inc. Dinuba California United States 93618
    4 Providence Clinical Research North Hollywood California United States 91606
    5 Hans Richard Barthel, M.D., Inc. Santa Barbara California United States 93108
    6 Westlake Medical Research Westlake Village California United States 91361
    7 Radiant Research Inc. - Denver Denver Colorado United States 80239
    8 Riverside Clinical Research Edgewater Florida United States 32132
    9 AppleMed Research, Inc. Miami Florida United States 33155
    10 Radiant Research Inc. Pinellas Park Florida United States 33781
    11 Injury Care Medical Center Boise Idaho United States 83713
    12 Global Scientific Innovations Evansville Indiana United States 47714
    13 Sundance Clinical Research, LLC Saint Louis Missouri United States 63141
    14 Manhattan Medical Research New York New York United States 10016
    15 Research Across America - NY New York New York United States 10022
    16 PMG Cary Medical Research Cary North Carolina United States 27518
    17 New Hope Clinical Research Charlotte North Carolina United States 28204
    18 PMG Research of Charlotte Charlotte North Carolina United States 28209
    19 PMG Research of Raleigh Raleigh North Carolina United States 27609
    20 PMG Research of Salisbury Salisbury North Carolina United States 28144
    21 Radiant Research Inc. - Akron Akron Ohio United States 44311
    22 Sterling Research Group, Ltd Cincinnati Ohio United States 45246
    23 Clinical Inquest Center Ltd. Dayton Ohio United States 45431
    24 Hillcrest Clinical Research Oklahoma City Oklahoma United States 73119
    25 Blair Orthopedic Associates, Inc. Altoona Pennsylvania United States 16602
    26 Clinical Research Solutions Franklin Tennessee United States 37064
    27 PMG Research of Knoxville Knoxville Tennessee United States 37912
    28 PMG Research of Knoxville Knoxville Tennessee United States 37938
    29 Clinical Research Solutions Smyrna Tennessee United States 37167
    30 Radiant Research Inc. - Salt Lake City Salt Lake City Utah United States 84123

    Sponsors and Collaborators

    • Biologische Heilmittel Heel GmbH

    Investigators

    • Principal Investigator: Nebojsa Skrepnik, MD, Tucson Orthopaedic Institute
    • Principal Investigator: Royal Anspach, MD, Clinical Research Advantage - Arizona II
    • Principal Investigator: Hans Barthel, MD, Hans Richard Barthel, M.D., Inc.
    • Principal Investigator: Shariar Cohen-Gadol, MD, Westlake Medical Research
    • Principal Investigator: David Bolshoun, MD, Radiant Research Inc. - Denver
    • Principal Investigator: Linda Murray, DO, Radiant Research Inc
    • Principal Investigator: Susan Hole, DO, Riverside Clinical Research
    • Principal Investigator: Agustin Latorre, MD, AppleMed Research, Inc.
    • Principal Investigator: Richard Radnovich, DO, Injury Care Medical Center
    • Principal Investigator: Moges Sisay, MD, Global Scientific Innovations
    • Principal Investigator: Larkin T Wadsworth, MD, Sundance Clinical Research, LLC
    • Principal Investigator: Kurian Abraham, MD, New Hope Clinical Research
    • Principal Investigator: Rakesh Patel, MD, PMG Research of Salisbury
    • Principal Investigator: George Raad, MD, PMG Research of Charlotte
    • Principal Investigator: Martin VanCleeff, MD, PMG Cary Medical Research
    • Principal Investigator: John Rubino, MD, PMG Research of Raleigh
    • Principal Investigator: Howard R Adelglass, MD, Research Across America - NY
    • Principal Investigator: Louis Re, MD, Manhattan Medical Research
    • Principal Investigator: Daniel Whitmer, MD, Clinical Inquest Center Ltd.
    • Principal Investigator: Jeffrey Klein, MD, Radiant Research Inc. - Akron
    • Principal Investigator: Rakesh Davit, MD, Sterling Research Group, Ltd.
    • Principal Investigator: Glenn Smith, DO, Hillcrest Clinical Research
    • Principal Investigator: Shawn Saylor, DO, Blair Orthopedic Associates, Inc
    • Principal Investigator: Alex Slandzicki, MD, Clinical Research Solutions
    • Principal Investigator: Sadia Dar, MD, Clinical Research Solutions
    • Principal Investigator: Rickey Manning, MD, PMG Research of Knoxville
    • Principal Investigator: Paul Wakefield, MD, PMG Research of Knoxville
    • Principal Investigator: Michael R Adams, MD, Radiant Research Inc. - Salt Lake City
    • Principal Investigator: Teresa Sligh, MD, Providence Clinical Research
    • Principal Investigator: David. Cardona, MD, Universal BioPharma Research Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Biologische Heilmittel Heel GmbH
    ClinicalTrials.gov Identifier:
    NCT01887678
    Other Study ID Numbers:
    • C1301
    First Posted:
    Jun 27, 2013
    Last Update Posted:
    Apr 2, 2018
    Last Verified:
    Mar 1, 2018
    Additional relevant MeSH terms:
    Osteoarthritis
    Osteoarthritis, Knee

    Study Results

    Participant Flow

    Recruitment Details A total of 28 investigational sites in the United States (US) entered at least one patient into the study database, 24 sites randomized at least one patient, 4 sites had Lead-In screening failures only.
    Pre-assignment Detail In total, 287 patients were enrolled into the study, 55 of them were Lead-In screening failures and therefore were not included.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Period Title: Overall Study
    STARTED 119 113
    COMPLETED 102 85
    NOT COMPLETED 17 28

    Baseline Characteristics

    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution Total
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. At baseline, patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Total of all reporting groups
    Overall Participants 119 113 232
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.7
    (9.11)
    59.7
    (8.68)
    60.2
    (8.90)
    Sex: Female, Male (Count of Participants)
    Female
    43
    36.1%
    46
    40.7%
    89
    38.4%
    Male
    76
    63.9%
    67
    59.3%
    143
    61.6%
    Region of Enrollment (participants) [Number]
    United States
    119
    100%
    113
    100%
    232
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Knee Pain as Measured by the WOMAC Osteoarthritis (OA) Index Pain Subscale (Section A, Items #1-5) Measured by 100 mm VAS
    Description Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess pain, scores from WOMAC Section A, items 1 to 5 are averaged to yield the Pain Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. A two-sided test of equality of the study drug (Traumeel®-Zeel®) and Placebo at level 0.05 was computed using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and the corresponding Baseline value of the primary efficacy variable as a covariate. The test decision was based on the (two-sided) p-value for the corresponding test of no treatment difference.
    Time Frame from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Mean (Standard Deviation) [units on a scale]
    -32.0
    (26.88)
    -25.5
    (24.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0383
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Square
    Estimated Value -6.37
    Confidence Interval (2-Sided) 95%
    -12.40 to -0.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.06
    Estimation Comments A negative value of the Least Square mean difference indicates a result in favor of Traumeel-Zeel.
    2. Secondary Outcome
    Title Pain Subscore (WOMAC Section A, Items #1-5) Measured by 100 mm VAS
    Description Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess pain, scores from WOMAC Section A, items 1 to 5 are averaged to yield the Pain Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in pain subscore were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.
    Time Frame from Baseline to post-Baseline visits except End of Study Visit (up to day 105)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Day 8±1
    -15.8
    (18.65)
    -13.6
    (19.11)
    Day 15±1
    -24.4
    (24.31)
    -18.5
    (20.02)
    Day 43±3
    -26.8
    (26.12)
    -21.5
    (21.62)
    Day 29±3
    -29.7
    (26.65)
    -22.4
    (22.33)
    Day 57±3
    -30.4
    (26.69)
    -22.7
    (23.37)
    Day 71±3
    -31.0
    (26.23)
    -23.3
    (24.38)
    Day 85±3
    -31.1
    (26.63)
    24.7
    (24.57)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 8±1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3715
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -2.15
    Confidence Interval (2-Sided) 95%
    -6.89 to 2.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 15±1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0293
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Square
    Estimated Value -5.87
    Confidence Interval (2-Sided) 95%
    -11.15 to -0.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 29±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0686
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -5.24
    Confidence Interval (2-Sided) 95%
    -10.88 to 0.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 43±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0150
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -7.25
    Confidence Interval (2-Sided) 95%
    -13.08 to -1.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 57±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0134
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -7.56
    Confidence Interval (2-Sided) 95%
    -13.54 to -1.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 71±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0121
    Comments
    Method Least Squares
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -7.60
    Confidence Interval (2-Sided) 95%
    -13.52 to -1.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 85±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0376
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -6.32
    Confidence Interval (2-Sided) 95%
    -12.28 to -0.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Stiffness Subscore (WOMAC Section B, Items #6-7) Measured by 100 mm VAS
    Description Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess stiffness, scores from WOMAC Section B, items 6 to 7 are averaged to yield the Stiffness Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in stiffness score were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.
    Time Frame from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Mean (Standard Deviation) [units on a scale]
    -34.1
    (28.16)
    -28.2
    (25.73)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1373
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -4.76
    Confidence Interval (2-Sided) 95%
    -11.05 to 1.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Physical Function Bubscore (WOMAC Section C, Items #8-24) Recorded on 100 mm VAS
    Description Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess physical function, scores from WOMAC Section C, items 8 to 24 are averaged to yield the Physical Function Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in Physical Function subscore were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.
    Time Frame from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 110
    Mean (Standard Deviation) [units on a scale]
    -31.1
    (27.38)
    -26.9
    (24.40)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1715
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -4.24
    Confidence Interval (2-Sided) 95%
    -10.33 to 1.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Total WOMAC Score (All Subscales) Recorded on 100 mm VAS
    Description Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. A total WOMAC score was computed by averaging all 24 possible responses. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. Changes in total WOMAC score were analyzed by using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and Baseline value as a covariate.
    Time Frame from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 110
    Mean (Standard Deviation) [units on a scale]
    -31.5
    (26.94)
    -26.7
    (24.14)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1211
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -4.77
    Confidence Interval (2-Sided) 95%
    -10.82 to 1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Patient Global Assessment (PGA)
    Description Patients made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".
    Time Frame from Baseline (Day 1, predose)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Very Good
    1
    0.8%
    0
    0%
    Good
    6
    5%
    7
    6.2%
    Fair
    62
    52.1%
    59
    52.2%
    Poor
    39
    32.8%
    43
    38.1%
    Very Poor
    8
    6.7%
    2
    1.8%
    Missing
    1
    0.8%
    0
    0%
    7. Secondary Outcome
    Title Patient Global Assessment (PGA)
    Description Patients made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".
    Time Frame End of Study Visit (up to Day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Very Good
    30
    25.2%
    22
    19.5%
    Good
    49
    41.2%
    39
    34.5%
    Fair
    31
    26.1%
    38
    33.6%
    Poor
    6
    5%
    11
    9.7%
    Very Poor
    1
    0.8%
    1
    0.9%
    Missing
    0
    0%
    0
    0%
    8. Secondary Outcome
    Title Physician Global Assessment (PhGA)
    Description Study Physicians made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".
    Time Frame Baseline (Day 1, predose)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Very Good
    0
    0%
    0
    0%
    Good
    7
    5.9%
    7
    6.2%
    Fair
    73
    61.3%
    77
    68.1%
    Poor
    34
    28.6%
    27
    23.9%
    Very Poor
    3
    2.5%
    0
    0%
    Missing
    0
    0%
    0
    0%
    9. Secondary Outcome
    Title Physician Global Assessment (PhGA)
    Description Study Physicians made an overall Global Assessment of the knee osteoarthritis with the assessment stages "Very good", "Good", "Fair", "Poor" and "Very poor".
    Time Frame End of Study Visit (up to Day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Very Good
    28
    23.5%
    20
    17.7%
    Good
    51
    42.9%
    38
    33.6%
    Fair
    34
    28.6%
    47
    41.6%
    Poor
    4
    3.4%
    4
    3.5%
    Very Poor
    0
    0%
    2
    1.8%
    Missing
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title Pain Immediately Following the 50-foot Walk (100 mm VAS)
    Description Changes of the target (treated) knee pain following a 50 feet walk self-assessed by the patients on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'.
    Time Frame Baseline (Day 1, predose) to post-Baseline visits (up to day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Day 8±1
    -26.5
    (22.39)
    -21.1
    (22.09)
    Day 15±1
    -37.4
    (23.80)
    -26.5
    (21.97)
    Day 29±3
    -38.1
    (25.37)
    -30.7
    (24.14)
    Day 43±3
    -42.3
    (25.13)
    -32.9
    (24.45)
    Day 57±3
    -43.0
    (25.04)
    -33.6
    (25.32)
    Day 71±3
    -42.6
    (25.31)
    -35.1
    (23.69)
    Day 85±3
    -41.3
    (27.29)
    -35.0
    (24.38)
    Day 119±3
    -42.3
    (26.33)
    -36.7
    (24.53)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 8±1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1128
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -4.97
    Confidence Interval (2-Sided) 95%
    -11.12 to 1.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 15±1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0013
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -10.49
    Confidence Interval (2-Sided) 95%
    -16.85 to -4.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 29±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0472
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -6.89
    Confidence Interval (2-Sided) 95%
    -13.69 to -0.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 43±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0109
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -8.82
    Confidence Interval (2-Sided) 95%
    -15.60 to -2.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 57±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0123
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -8.88
    Confidence Interval (2-Sided) 95%
    -15.80 to -1.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 71±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0425
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -6.88
    Confidence Interval (2-Sided) 95%
    -13.52 to -0.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 85±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1199
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -5.51
    Confidence Interval (2-Sided) 95%
    -12.47 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 119±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1575
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -4.96
    Confidence Interval (2-Sided) 95%
    -11.86 to 1.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Time to Walking (50-foot Walk Test)
    Description Changes in time to walk 50 feet (seconds)
    Time Frame Baseline (Day 1, predose) to post-Baseline visits (up to day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Day 8±1
    -2.8
    (7.38)
    -2.5
    (5.91)
    Day 15±1
    -3.0
    (7.25)
    -2.7
    (6.90)
    Day 29±3
    -3.7
    (8.28)
    -3.5
    (7.94)
    Day 43±3
    -4.4
    (9.23)
    -3.9
    (8.05)
    Day 57±3
    -4.1
    (8.24)
    -3.7
    (9.02)
    Day 71±3
    -4.6
    (9.59)
    -4.3
    (9.63)
    Day 85±3
    -4.6
    (9.84)
    -4.9
    (10.26)
    Day 119±3
    -4.8
    (9.66)
    -4.6
    (10.24)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 8±1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6346
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.28
    Confidence Interval (2-Sided) 95%
    -1.45 to 0.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 15±1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6458
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.28
    Confidence Interval (2-Sided) 95%
    -1.49 to 0.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 29±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7581
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -1.35 to 0.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 43±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.3350
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.49
    Confidence Interval (2-Sided) 95%
    -1.48 to 0.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 57±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4419
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -1.44 to 0.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 71±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.4460
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.37
    Confidence Interval (2-Sided) 95%
    -1.32 to 0.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 85±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6552
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value 0.25
    Confidence Interval (2-Sided) 95%
    -0.84 to 1.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments Day 119±3
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7443
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -1.33 to 0.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Other Pre-specified Outcome
    Title Serious Adverse Events
    Description Total number of patients affected.
    Time Frame Start of Lead-In period until individual study end, up to 16 weeks.

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 patients to Placebo and all randomized patients were included in the Safety Set. MedDRA Version 16.0 terminology
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 119 113
    Total number of patients affected
    2
    1.7%
    1
    0.9%
    Bradycardia and Hyperglycaemia
    1
    0.8%
    0
    0%
    Haematemesis
    1
    0.8%
    0
    0%
    Transient ischemic attack
    0
    0%
    1
    0.9%
    13. Other Pre-specified Outcome
    Title Each Adverse Event (AE)
    Description Total number of patients affected.
    Time Frame Starting at Visit 2/ Start of Lead-In period (Day 7 up to day 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 patients to Placebo and all randomized patients were included in the Safety Set. 8 patients without any injection (not randomized) reported 12 adverse events
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 119 113
    Number [participants]
    64
    53.8%
    43
    38.1%
    14. Other Pre-specified Outcome
    Title Incidence of Treatment Emergent Adverse Events (TEAEs)
    Description Total number of patients affected.
    Time Frame during the treatment period and follow up period (Days 11 to 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 patients to Placebo and all randomized patients were included in the Safety Set. MedDRA Version 16.0 terminology. Adverse events during treatment (treatment-emergent) in 5% or more of total study patients
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 119 113
    Total Number of Patients affected
    64
    53.8%
    43
    38.1%
    Musculoskeletal and connective tissue disorders
    26
    21.8%
    14
    12.4%
    Infections and infestations
    12
    10.1%
    10
    8.8%
    Nervous system disorders
    14
    11.8%
    8
    7.1%
    Skin and subcutaneous tissue disorders
    14
    11.8%
    9
    8%
    General disorders and administration site conditio
    11
    9.2%
    8
    7.1%
    Injury, poisoning and procedural complications
    6
    5%
    6
    5.3%
    15. Other Pre-specified Outcome
    Title Proportion of Patients Who Discontinued Due to an AE
    Description Total number of patients affected.
    Time Frame All visits (Days 1 up to 119)

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 patients to Placebo and all randomized patients were included in the Safety Set. Medical Dictionary for Regulatory Activities (MedDRA) Version 16.0 terminology.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 119 113
    Total number of patients affected
    3
    2.5%
    4
    3.5%
    Injection site joint pain
    1
    0.8%
    1
    0.9%
    Injection site vesicles
    1
    0.8%
    0
    0%
    Haemarthrosis
    1
    0.8%
    0
    0%
    Muscle tightness
    0
    0%
    1
    0.9%
    Pain in extremity
    0
    0%
    1
    0.9%
    Nephrolithiasis
    0
    0%
    1
    0.9%
    Rash maculopapular
    0
    0%
    1
    0.9%
    16. Secondary Outcome
    Title Time to 50% Pain Relief (Study Population Measure Statistically Derived)
    Description Changes of the target (treated) knee pain following a 50 feet walk self-assessed by the patients on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. The time to 50% pain relief were statistical exercises and were analyzed for each individual patient from their self-assessment.
    Time Frame Statistically derived

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    After 1st Injection
    15
    22
    After 2nd Injection
    22
    34
    After 3rd Injection
    29
    50
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments After first injection of study drug
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2164
    Comments
    Method Log Rank
    Comments Results of Kaplan-Meier Analysis with p-value from 2-sided log-rank test for equality of survival functions
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments After second injection of study drug
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1651
    Comments Results of Kaplan-Meier Analysis with p-value from 2-sided log-rank test for equality of survival functions
    Method Log Rank
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments After third injection of study drug
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2220
    Comments
    Method Log Rank
    Comments Results of Kaplan-Meier Analysis with p-value from 2-sided log-rank test for equality of survival functions
    17. Secondary Outcome
    Title Patients Achieving 100% Pain Relief
    Description Changes of the target (treated) knee pain following a 50 feet walk self-assessed by the patients on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. The time to 100% pain relief were statistical exercises and were analyzed for each individual patient from their self-assessment, however, the prevalence of 100% pain relief did not support an estimate for the median time. The number of patients who reached 100% pain relief is reported and the log rank test for difference in time to 100% pain relief was calculated for each injection.
    Time Frame Statistically derived

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    After 1st Injection
    26
    21.8%
    12
    10.6%
    After 2nd Injection
    25
    21%
    12
    10.6%
    After 3rd Injection
    26
    21.8%
    11
    9.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments After first injection of study drug
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0264
    Comments
    Method Log Rank
    Comments For equality of survival functions
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments After second injection of study drug
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0346
    Comments
    Method Log Rank
    Comments For equality of survival functions
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Co-administered Traumeel® and Zeel®, Placebo Injectable Solution
    Comments After third injection of study drug
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0172
    Comments
    Method Log Rank
    Comments For equality of survival functions
    18. Secondary Outcome
    Title Time to and Use of Rescue Medication (Acetaminophen up to 3000 mg Per Day for Breakthrough Pain) (Study Population Measure Statistically Derived) - Patients Use
    Description Time to and use of rescue medication (acetaminophen up to 3000 mg per day for breakthrough pain) as reported by the patients. Patients who used any rescue medication during the study.
    Time Frame Statistically derived

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Number [participants]
    82
    68.9%
    72
    63.7%
    19. Secondary Outcome
    Title Time to and Use of Rescue Medication (Acetaminophen up to 3000 mg Per Day for Breakthrough Pain) (Study Population Measure Statistically Derived). Tablets Taken.
    Description Time to and use of rescue medication (acetaminophen up to 3000 mg per day for breakthrough pain) (study population measure statistically derived). Total number of tablets taken as reported by patient.
    Time Frame Statistically derived

    Outcome Measure Data

    Analysis Population Description
    119 patients were randomized to Traumeel/Zeel and 113 to Placebo and all were included in the Safety Set. Two patients in each group could not be evaluated for primary efficacy. 117 patients in Traumeel/Zeel and 111 patients in Placebo formed the Full Analysis - efficacy. For missing values, Last-observation carried forward (LOCF) was used.
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    Measure Participants 117 111
    Mean (Standard Deviation) [Tablets]
    49.0
    (64.64)
    55.8
    (59.71)

    Adverse Events

    Time Frame Study Duration, 9 Months.
    Adverse Event Reporting Description The safety analysis included 232 randomized patients receiving at least one injection. 119 patients were randomized to Traumeel/Zeel and 113 patients to Placebo
    Arm/Group Title Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Arm/Group Description Patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a Traumeel/Zeel injection solution administered once weekly into the target knee on Study Days 1, 8 and 15. At baseline, patients with documented diagnosis of primary osteoarthritis of the based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment with an age of between 45 to 80 years and the ability to understand the explanations and instructions given by the study physician got a placebo injection solution administered once weekly into the target knee on Study Days 1, 8 and 15.
    All Cause Mortality
    Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/119 (1.7%) 1/113 (0.9%)
    Cardiac disorders
    Bradycardia 1/119 (0.8%) 1 0/113 (0%) 0
    Gastrointestinal disorders
    Haematemesis 1/119 (0.8%) 1 0/113 (0%) 0
    Metabolism and nutrition disorders
    Hyperglycemia 1/119 (0.8%) 1 0/113 (0%) 0
    Nervous system disorders
    Transient Ischemic Attack 0/119 (0%) 0 1/113 (0.9%) 1
    Other (Not Including Serious) Adverse Events
    Co-administered Traumeel® and Zeel® Placebo Injectable Solution
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 64/119 (53.8%) 43/113 (38.1%)
    Blood and lymphatic system disorders
    Lymph node pain 0/119 (0%) 1/113 (0.9%)
    Cardiac disorders
    Bradycardia 1/119 (0.8%) 0/113 (0%)
    Ear and labyrinth disorders
    Ear pain 1/119 (0.8%) 0/113 (0%)
    Middle ear effusion 0/119 (0%) 1/113 (0.9%)
    Vertigo 1/119 (0.8%) 0/113 (0%)
    Eye disorders
    Conjunctivitis 1/119 (0.8%) 0/113 (0%)
    Dacryostenosis acquired 1/119 (0.8%) 0/113 (0%)
    Dry eye 1/119 (0.8%) 0/113 (0%)
    Lenticular opacities 0/119 (0%) 1/113 (0.9%)
    Presbyopia 1/119 (0.8%) 0/113 (0%)
    Gastrointestinal disorders
    Nausea 0/119 (0%) 2/113 (1.8%)
    Toothache 1/119 (0.8%) 1/113 (0.9%)
    Abdominal pain 1/119 (0.8%) 0/113 (0%)
    Abdominal pain upper 1/119 (0.8%) 0/113 (0%)
    Constipation 1/119 (0.8%) 0/113 (0%)
    Diarrhea 1/119 (0.8%) 0/113 (0%)
    Haematemesis 1/119 (0.8%) 0/113 (0%)
    Vomiting 1/119 (0.8%) 0/113 (0%)
    General disorders
    Injection site joint pain 4/119 (3.4%) 1/113 (0.9%)
    Pain 5/119 (4.2%) 0/113 (0%)
    Injection site vesicles 1/119 (0.8%) 1/113 (0.9%)
    Pyrexia 0/119 (0%) 2/113 (1.8%)
    Injection site bruising 1/119 (0.8%) 0/113 (0%)
    Injection site erythema 0/119 (0%) 1/113 (0.9%)
    Injection site joint swelling 0/119 (0%) 1/113 (0.9%)
    Injection site scab 0/119 (0%) 1/113 (0.9%)
    Oedema peripheral 0/119 (0%) 1/113 (0.9%)
    Spinal pain 0/119 (0%) 1/113 (0.9%)
    Immune system disorders
    Seasonal allergy 1/119 (0.8%) 0/113 (0%)
    Infections and infestations
    Nasopharyngitis 4/119 (3.4%) 1/113 (0.9%)
    Urinary tract infection 3/119 (2.5%) 1/113 (0.9%)
    Upper respiratory tract infection 1/119 (0.8%) 2/113 (1.8%)
    Bronchitis 2/119 (1.7%) 0/113 (0%)
    Sinusitis 1/119 (0.8%) 1/113 (0.9%)
    Gastroenteritis viral 0/119 (0%) 1/113 (0.9%)
    Gingival abscess 0/119 (0%) 1/113 (0.9%)
    Kidney infection 0/119 (0%) 1/113 (0.9%)
    Lower respiratory tract infection 1/119 (0.8%) 0/113 (0%)
    Pyoderma 0/119 (0%) 1/113 (0.9%)
    Tooth abscess 0/119 (0%) 1/113 (0.9%)
    Injury, poisoning and procedural complications
    Contusion 1/119 (0.8%) 2/113 (1.8%)
    Excoriation 2/119 (1.7%) 0/113 (0%)
    Procedural pain 1/119 (0.8%) 1/113 (0.9%)
    Animal bite 1/119 (0.8%) 0/113 (0%)
    Fall 1/119 (0.8%) 0/113 (0%)
    Foot fracture 0/119 (0%) 1/113 (0.9%)
    Hand fracture 1/119 (0.8%) 0/113 (0%)
    Ligament sprain 1/119 (0.8%) 0/113 (0%)
    Meniscus injury 0/119 (0%) 1/113 (0.9%)
    Muscle strain 0/119 (0%) 1/113 (0.9%)
    Rib fracture 1/119 (0.8%) 0/113 (0%)
    Investigations
    Blood lactate dehydrogenase increased 1/119 (0.8%) 1/113 (0.9%)
    Blood pressure increased 1/119 (0.8%) 1/113 (0.9%)
    Blood urine present 0/119 (0%) 1/113 (0.9%)
    Eosinophil count increased 0/119 (0%) 1/113 (0.9%)
    Heart rate increased 0/119 (0%) 1/113 (0.9%)
    Neutrophil count decreased 0/119 (0%) 1/113 (0.9%)
    Red blood cell count increased 0/119 (0%) 1/113 (0.9%)
    Metabolism and nutrition disorders
    Fluid retention 0/119 (0%) 2/113 (1.8%)
    Gout 0/119 (0%) 1/113 (0.9%)
    Hyperglycaemia 1/119 (0.8%) 0/113 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 9/119 (7.6%) 8/113 (7.1%)
    Joint swelling 3/119 (2.5%) 6/113 (5.3%)
    Pain in extremity 7/119 (5.9%) 2/113 (1.8%)
    Back pain 3/119 (2.5%) 1/113 (0.9%)
    Joint crepitation 2/119 (1.7%) 0/113 (0%)
    Joint range of motion decreased 2/119 (1.7%) 0/113 (0%)
    Muscle spasm 2/119 (1.7%) 0/113 (0%)
    Musculoskeletal pain 1/119 (0.8%) 1/113 (0.9%)
    Bursitis 1/119 (0.8%) 0/113 (0%)
    Haemarthrosis 1/119 (0.8%) 0/113 (0%)
    Joint stiffness 0/119 (0%) 1/113 (0.9%)
    Lumbar spinal stenosis 1/119 (0.8%) 0/113 (0%)
    Muscle tightness 0/119 (0%) 1/113 (0.9%)
    Neck pain 0/119 (0%) 1/113 (0.9%)
    Rotator cuff syndrome 0/119 (0%) 1/113 (0.9%)
    Seronegative arthritis 0/119 (0%) 1/113 (0.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 1/119 (0.8%) 0/113 (0%)
    Nervous system disorders
    Headache 10/119 (8.4%) 3/113 (2.7%)
    Presyncope 2/119 (1.7%) 1/113 (0.9%)
    Sciatica 2/119 (1.7%) 1/113 (0.9%)
    Dizziness 0/119 (0%) 2/113 (1.8%)
    Burning sensation 0/119 (0%) 1/113 (0.9%)
    Sinus headache 0/119 (0%) 1/113 (0.9%)
    Transient ischaemic attack 0/119 (0%) 1/113 (0.9%)
    Psychiatric disorders
    Insomnia 0/119 (0%) 2/113 (1.8%)
    Renal and urinary disorders
    Nephrolithiasis 1/119 (0.8%) 1/113 (0.9%)
    Reproductive system and breast disorders
    Breast pain 1/119 (0.8%) 0/113 (0%)
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 1/119 (0.8%) 2/113 (1.8%)
    Sinus congestion 3/119 (2.5%) 0/113 (0%)
    Oropharyngeal pain 1/119 (0.8%) 1/113 (0.9%)
    Cough 1/119 (0.8%) 0/113 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis contact 1/119 (0.8%) 1/113 (0.9%)
    Ingrowing nail 1/119 (0.8%) 0/113 (0%)
    Rash maculo-papular 0/119 (0%) 1/113 (0.9%)
    Skin irritation 1/119 (0.8%) 0/113 (0%)
    Skin ulcer 1/119 (0.8%) 0/113 (0%)
    Vitiligo 0/119 (0%) 1/113 (0.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Investigator agreements in place restricting the PI from independently publishing the study results.

    Results Point of Contact

    Name/Title Christine Frank, PhD, Global Clinical Project Manager
    Organization Biologische Heilmittel Heel GmbH
    Phone +49 7221 501 3188
    Email christine.frank@heel.com
    Responsible Party:
    Biologische Heilmittel Heel GmbH
    ClinicalTrials.gov Identifier:
    NCT01887678
    Other Study ID Numbers:
    • C1301
    First Posted:
    Jun 27, 2013
    Last Update Posted:
    Apr 2, 2018
    Last Verified:
    Mar 1, 2018