PMID- 33059293
OWN - NLM
STAT- MEDLINE
DCOM- 20210929
LR  - 20210929
IS  - 1532-866X (Electronic)
IS  - 0049-0172 (Linking)
VI  - 50
IP  - 6
DP  - 2020 Dec
TI  - A novel diclofenac gel (AMZ001) applied once or twice daily in subjects with 
      painful knee osteoarthritis: A randomized, placebo-controlled clinical trial.
PG  - 1203-1213
LID - S0049-0172(20)30250-X [pii]
LID - 10.1016/j.semarthrit.2020.09.007 [doi]
AB  - PURPOSE: Osteoarthritis Research Society International (OARSI) Expert Consensus 
      Guidelines recommend topical non-steroidal anti-inflammatory drugs as first-line 
      medications for osteoarthritis (OA) knee pain, but several voluminous daily 
      applications are required to achieve efficacy. There is a need to develop new and 
      improved topical analgesics with a faster onset, longer duration of action, and 
      the requirement to apply less gel. This trial investigated the safety and 
      efficacy of a new 3.06% diclofenac gel (AMZ001) in subjects with knee OA. 
      METHODS: In total, 444 subjects (AMZ001 twice daily (BID) [n = 121], AMZ001 once 
      daily (QD) + placebo QD [n = 121], placebo BID [n = 121], or Voltaren 1% 4-times 
      daily [n = 81]) were enrolled. All except Voltaren 1% (single-blinded) were 
      applied topically in a double-blind manner for a total of 4-weeks. The primary 
      endpoint was the change from baseline to week 4 in the WOMAC pain sub-score in 
      the target knee. Secondary and exploratory endpoints included additional efficacy 
      measures (WOMAC total score, WOMAC function and stiffness sub-scores, WOMAC pain 
      weight-bearing and non-weight-bearing sub-scores, ICOAP, chair-stand test, 
      OMERACT-OARSI responder rate, PGA, WPAI, EQ-5D, rescue medication use, 
      satisfaction questionnaire) and safety. RESULTS: Treatment with AMZ001 QD was 
      effective at reducing WOMAC pain sub-scores vs placebo (estimated treatment 
      difference [ETD]: -4.61 [95% confidence interval (CI): -9.09, -0.12]; 
      p = 0.0440); however, BID application was not (ETD: -3.76 [95% CI: -8.21, 0.68]; 
      p = 0.0969). For several secondary endpoints, changes from baseline to week 4 
      conferred nominally statistically significant improvements in favor of AMZ001 vs 
      placebo, including PGA score (AMZ001 BID vs placebo, ETD: -0.61 [95% CI: -1.11, 
      -0.11]; p = 0.0162; AMZ001 QD vs placebo, ETD: -0.63 [95% CI: -1.13, -0.13]; 
      p = 0.0134), WPAI overall work impairment score (AMZ001 QD vs placebo, ETD: 
      -10.44 [95% CI: -20.84, -0.04]; p = 0.0492), and EQ-5D VAS score (AMZ001 BID vs 
      placebo, ETD: 4.70 [95% CI: 0.55, 8.85]; p = 0.0264). Post-hoc analysis excluding 
      11-14 subjects per group with pain scores that decreased between screening and 
      baseline suggests a consistent effect of both AMZ001 QD (ETD: -5.84 [95% CI: 
      -10.71, -0.97]; p = 0.0189) and BID (ETD: -5.35 [95% CI: -10.16, -0.54]; 
      p = 0.0292) in reducing WOMAC pain sub-scores vs placebo. In general, treatment 
      satisfaction was high, as measured by the satisfaction questionnaire. The 
      frequency and incidence of adverse events (AEs) was greatest in the placebo 
      group. Most AEs (>99%) were of mild or moderate severity. There were no serious 
      AEs. There were no notable effects of any treatment on vital signs, ECGs, 
      physical examination findings, or other laboratory assessments. CONCLUSIONS: 
      Treatment with AMZ001 BID for 4 weeks improved WOMAC pain sub-scores; however, 
      only QD application conferred nominally statistically significant improvements vs 
      placebo. AMZ001 was generally well tolerated.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Bihlet, Asger Reinstrup
AU  - Bihlet AR
AD  - Nordic Bioscience Clinical Development, Denmark. Electronic address: 
      abi@nordicbio.com.
FAU - Byrjalsen, Inger
AU  - Byrjalsen I
AD  - Nordic Bioscience Clinical Development, Denmark.
FAU - Simon, Lee S
AU  - Simon LS
AD  - SDG LLC, Cambridge, Massachusetts, United States.
FAU - Carrara, Dario
AU  - Carrara D
AD  - Amzell B.V., Hoofddorp, the Netherlands.
FAU - Delpy, Laetitia
AU  - Delpy L
AD  - Amzell B.V., Hoofddorp, the Netherlands.
FAU - Derne, Caroline
AU  - Derne C
AD  - Amzell B.V., Hoofddorp, the Netherlands.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200924
PL  - United States
TA  - Semin Arthritis Rheum
JT  - Seminars in arthritis and rheumatism
JID - 1306053
RN  - 144O8QL0L1 (Diclofenac)
SB  - IM
MH  - *Diclofenac/therapeutic use
MH  - Humans
MH  - Knee Joint
MH  - *Osteoarthritis, Knee/drug therapy
MH  - Pain
MH  - Treatment Outcome
OTO - NOTNLM
OT  - AMZ001
OT  - Diclofenac
OT  - Osteoarthritis
OT  - Pain, Quality of life
OT  - Topical
COIS- Declaration of Competing Interest Laetitia Delpy, Caroline Derne and Dario 
      Carrara are employed by Ferring Pharmaceuticals and conduct work for Amzell B.V. 
      Lee S Simon is a consultant to Amzell B.V. Asger R. Bihlet and Inger Byrjalsen 
      are employed by Nordic Bioscience Clinical Development A/S which conducted the 
      current trial project for Amzell B.V.
EDAT- 2020/10/16 06:00
MHDA- 2021/09/30 06:00
CRDT- 2020/10/15 20:16
PHST- 2020/06/17 00:00 [received]
PHST- 2020/09/07 00:00 [revised]
PHST- 2020/09/09 00:00 [accepted]
PHST- 2020/10/16 06:00 [pubmed]
PHST- 2021/09/30 06:00 [medline]
PHST- 2020/10/15 20:16 [entrez]
AID - S0049-0172(20)30250-X [pii]
AID - 10.1016/j.semarthrit.2020.09.007 [doi]
PST - ppublish
SO  - Semin Arthritis Rheum. 2020 Dec;50(6):1203-1213. doi: 
      10.1016/j.semarthrit.2020.09.007. Epub 2020 Sep 24.