Study of Intra-articular Injections vs Placebo in Patient... | NCT01887678

Label	Type	Description	Intervention Names
Traumeel® / Zeel® Injectable Solution	Experimental	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
Placebo injectable solution	Placebo Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Traumeel® / Zeel® Injectable Solution	Drug	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.

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

Measure	Description	Time Frame
Pain Subscore (WOMAC Section A, Items #1-5) Measured by 100 mm VAS	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.

Measure	Description	Time Frame
Serious Adverse Events	Total number of patients affected.	Start of Lead-In period until individual study end, up to 16 weeks.
Each Adverse Event (AE)	Total number of patients affected.

Eligibility Module

Eligibility Criteria

Inclusion Criteria (Screening Visit 1):

Osteoarthritis (OA) of the knee by American College of Rheumatology criteria
Men or women between 45-80 years of age.
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.
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.
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
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.
Willingness to stop all OA treatments.
Fully informed of the risks of entering the study and willing to provide written consent to enter the study.
Able to understand and be willing to comply with all study requirements, particularly the weekly injection regimen for administration of study drug.
Primary complaint is pain immediately following an unassisted 50-foot walk. They must show:
1. moderate to severe pain score in the target knee as demonstrated by 40 - 90 mm recorded on a 100 mm VAS, and
2. 20 mm increase in pain from their screening visit pain score (a "flare")
3. pain in the non-target (contralateral) knee must </= 30 mm on a 100 mm VAS

Exclusion Criteria:

Known hypersensitivity or allergy to any of the components of Traumeel or Zeel
Known hypersensitivity or allergy to acetaminophen.
Has body mass index (BMI) >38 kg/m2.
Avoidance of, or aversion to, nonprescription medications.
Clinical symptoms of meniscal instability or significant valgus/ varus that requires corrective osteotomy
Any major injury or surgery to the target knee in the prior 12 months.
One or a combination of the following co-morbidities:
1. other inflammatory arthropathies, gout or pseudogout within previous 6 months
2. avascular necrosis
3. severe bone or joint deformity in target knee
4. osteonecrosis of either knee
5. fibromyalgia
6. pes anserine bursitis
7. lumbar radiculopathy with referred pain to either knee
8. neurogenic or vascular claudication
9. significant anterior knee pain due to diagnosed isolated patella-femoral syndrome in the target knee
10. target knee joint infection or skin disorder/infection to the area surrounding the knee within previous 6 months
11. current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin)
Participated in any experimental drug or device study within the prior one (1) month and/or IA injections six (6) months.
Referred pain from other joints
Significantly debilitating concurrent infection(s)
Significant ligamentous instability
Any prior viscosupplementation therapy (in target knee) within 6 months prior to Screening
Systemic or IA injection of corticosteroids in any joint within 3 months of enrollment
Therapy with oral hyaluronic acid products, and/or oral pharmaceutical products containing glucosamine and/or chondroitin sulphate and/or diacerein
Therapy with opioids within the last 90 days including intra-dermal delivery systems (patches)
Therapy with autologous stem cells
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.
Concomitant inflammatory or other rheumatologic, neurological or cardiovascular diseases which could affect the evaluation of knee pain
Ongoing litigation for workers compensation for musculoskeletal injuries or disorders
Use of alcohol of more than 4 drinks per day
Clinically important axial deviation (varus, valgus) greater than 15 degrees
Concomitant severe OA of the hip or other joints, which might interfere with the assessments required by the study
Painful knee conditions other than OA (e.g., Paget's disease)
Hemiparesis of lower limbs
Significant planned surgery to lower limbs, which might interfere with the patient's ability to comply with study requirements
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
Presence of infections and/or skin diseases in the area of the injection site such as psoriasis
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.
Clinically significant abnormal laboratory values.
Patients who are likely to be non-compliant or uncooperative during the study.

Name	Affiliation	Role
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

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Advantage - Arizona II		Phoenix	Arizona	85050	United States
Tucson Orthopaedic Institute

PubMed Identifier	Type	Citation	Retractions
	Result	Lozada CJ, del Rio E, Reitberg DP, Smith RA, Kahn CB, Moskowitz RW. A double-blind, randomized, saline-controlled study of the efficacy and safety of co-administered intra-articular injections of Tr14 and Ze14 for treatment of painful osteoarthritis of the knee: The MOZArT trial. Eur J Integr Med 2017;13:54-63. DOI: 10.1016/j.eujim.2017.07.005;

ID	Title	Description
FG000	Co-administered Traumeel® and Zeel®	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Knee Pain as Measured by the WOMAC Osteoarthritis (OA) Index Pain Subscale (Section A, Items #1-5) Measured by 100 mm VAS

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.

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.

Posted

Mean

Standard Deviation

units on a scale

from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Units	Counts
Participants	OG000117 OG001111

Title

Denominators

Categories

Title	Measurements
	OG000-32.0± 26.88 OG001-25.5± 24.08

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.0383		Least Square	-6.37	Standard Error of the Mean	3.06	2-Sided	95	-12.40	-0.35			A negative value of the Least Square mean difference indicates a result in favor of Traumeel-Zeel.		Superiority or Other

Secondary

Pain Subscore (WOMAC Section A, Items #1-5) Measured by 100 mm VAS

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.

Posted

Mean

Standard Deviation

units on a scale

from Baseline to post-Baseline visits except End of Study Visit (up to day 105)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.

Secondary

Stiffness Subscore (WOMAC Section B, Items #6-7) Measured by 100 mm VAS

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.

Posted

Mean

Standard Deviation

units on a scale

from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.

Secondary

Physical Function Bubscore (WOMAC Section C, Items #8-24) Recorded on 100 mm VAS

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.

Posted

Mean

Standard Deviation

units on a scale

from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.

Secondary

Total WOMAC Score (All Subscales) Recorded on 100 mm VAS

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.

Posted

Mean

Standard Deviation

units on a scale

from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.

Secondary

Patient Global Assessment (PGA)

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

Posted

Number

participants

from Baseline (Day 1, predose)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Patient Global Assessment (PGA)

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

Posted

Number

participants

End of Study Visit (up to Day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Physician Global Assessment (PhGA)

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

Posted

Number

participants

Baseline (Day 1, predose)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Physician Global Assessment (PhGA)

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

Posted

Number

participants

End of Study Visit (up to Day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Pain Immediately Following the 50-foot Walk (100 mm VAS)

Posted

Mean

Standard Deviation

units on a scale

Baseline (Day 1, predose) to post-Baseline visits (up to day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Time to Walking (50-foot Walk Test)

Changes in time to walk 50 feet (seconds)

Posted

Mean

Standard Deviation

seconds

Baseline (Day 1, predose) to post-Baseline visits (up to day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Other Pre-specified

Serious Adverse Events

Total number of patients affected.

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

Posted

Number

participants

Start of Lead-In period until individual study end, up to 16 weeks.

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Other Pre-specified

Each Adverse Event (AE)

Total number of patients affected.

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

Posted

Number

participants

Starting at Visit 2/ Start of Lead-In period (Day 7 up to day 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Other Pre-specified

Incidence of Treatment Emergent Adverse Events (TEAEs)

Total number of patients affected.

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

Posted

Number

participants

during the treatment period and follow up period (Days 11 to 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Other Pre-specified

Proportion of Patients Who Discontinued Due to an AE

Total number of patients affected.

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.

Posted

Number

participants

All visits (Days 1 up to 119)

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Time to 50% Pain Relief (Study Population Measure Statistically Derived)

Posted

Median

95% Confidence Interval

days

Statistically derived

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

Patients Achieving 100% Pain Relief

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.

Posted

Number

participants

Statistically derived

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution

Secondary

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

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.

Posted

Number

participants

Statistically derived

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Secondary

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

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.

Posted

Mean

Standard Deviation

Tablets

Statistically derived

ID	Title	Description
OG000	Co-administered Traumeel® and Zeel®	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.
OG001	Placebo Injectable Solution	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.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0009 affected119 at risk EG0018 affected113 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0003 affected119 at risk EG0016 affected113 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0007 affected119 at risk EG0012 affected113 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0003 affected119 at risk EG0011 affected113 at risk
Joint crepitation	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0010 affected113 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0010 affected113 at risk
Muscle spasm	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0010 affected113 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Seronegative arthritis	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Nasopharyngitis	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0004 affected119 at risk EG0011 affected113 at risk
Urinary tract infection	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0003 affected119 at risk EG0011 affected113 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0012 affected113 at risk
Bronchitis	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0010 affected113 at risk
Sinusitis	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Gingival abscess	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Kidney infection	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Pyoderma	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Tooth abscess	Infections and infestations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Headache	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG00010 affected119 at risk EG0013 affected113 at risk
Presyncope	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0011 affected113 at risk
Sciatica	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0011 affected113 at risk
Dizziness	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0012 affected113 at risk
Burning sensation	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Sinus headache	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Injection site joint pain	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0004 affected119 at risk EG0011 affected113 at risk
Pain	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0005 affected119 at risk EG0010 affected113 at risk
Injection site vesicles	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Pyrexia	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0012 affected113 at risk
Injection site bruising	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Injection site erythema	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Injection site joint swelling	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Injection site scab	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Oedema peripheral	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Spinal pain	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0012 affected113 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0002 affected119 at risk EG0010 affected113 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Nausea	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0012 affected113 at risk
Toothache	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Constipation	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Haematemesis	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Vomiting	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0012 affected113 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0003 affected119 at risk EG0010 affected113 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Blood pressure increased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Blood urine present	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Eosinophil count increased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Heart rate increased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Neutrophil count decreased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Red blood cell count increased	Investigations	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Conjunctivitis	Eye disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Dacryostenosis acquired	Eye disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Dry eye	Eye disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Lenticular opacities	Eye disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Presbyopia	Eye disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0012 affected113 at risk
Gout	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Ear pain	Ear and labyrinth disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Middle ear effusion	Ear and labyrinth disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Insomnia	Psychiatric disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0012 affected113 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0011 affected113 at risk
Lymph node pain	Blood and lymphatic system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 affected119 at risk EG0011 affected113 at risk
Bradycardia	Cardiac disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Seasonal allergy	Immune system disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk
Breast pain	Reproductive system and breast disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 affected119 at risk EG0010 affected113 at risk

ID	Term
D010003	Osteoarthritis
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases

ID	Term
C433370	Traumeel S
D012965	Sodium Chloride

ID	Term
D002712	Chlorides
D006851	Hydrochloric Acid
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017670	Sodium Compounds

ID	Title	Description
BG000	Co-administered Traumeel® and Zeel®	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.
BG001	Placebo Injectable Solution	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Co-administered Traumeel® and Zeel®	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.			2	119	64	119
EG001	Placebo Injectable Solution	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.			1	113	43	113