TRAUMEEL® PRODUCT MONOGRAPH38

Traumeel® in co-administration with Zeel® T (intra-articular injections) for the treatment of knee osteoarthritis: the MOZArT study

Lozada C, del Rio E, Reitberg D, Smith R, Kahn C, 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.

STUDY DESIGN FORMULATION INDICATION(S) Multi-center, randomized, placebo- controlled double-blind trial.

Traumeel® injection combined with Zeel® T injection.

Moderate-to severe chronic knee osteoarthritis.

Study design Patients with moderate-to-severe chronic knee OA were randomized to receive 3

weekly intra-articular (IA) injections of: Traumeel® and Zeel® T n=119 saline solution n=113.

The study lasted 17 weeks (screening, wash-out, lead-in, treatment period and follow-up period). Study visits were at screening/start of wash-out period, start of lead-in period,

baseline/randomization/first dose (Day 1), second dose (Day 8), third dose (Day 15), site visits on alternate weeks for 12 weeks, with phone calls to patients in-between visits (every other week).

End points Primary endpoint

Change in knee pain from Baseline (Day 1, predose) to End-of-Study (Day 99) as measured by the WOMAC* OA Pain Subscore (A) 100 mm VAS

Secondary endpoints Total WOMAC and sub scores for stiffness (B), and physical function (C) Change in pain following a 50 ft walk (100 mm VAS) Change in time to walk (50 ft walk test) Consumption of rescue medication Patient and physician global assessments.

Clinical relevance was assessed, in a post-hoc analysis, by comparing treatments with respect to the proportions of patients for whom the improvements from baseline in WOMAC Pain Subscale met or exceeded a Minimum Clinically Important Improvement (MCII). The MCII was set at the highest level (36.6 mm) suggested for 100 mm VAS assessments of knee OA pain.65

Safety was assessed by monitoring of vital signs, physical examinations of the target knee, adverse events and concomitant medications.

* Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): To assess pain, stiffness, and physical function in patients with hip and / or knee osteoarthritis (OA).