A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis

Baerwald, C.; Goebel, K. M.; Krause, Andreas; Heymanns, Jochen

doi:10.1002/art.1780330517

Cited by 4 publications

(1 citation statement)

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“…Both compounds also markedly reduce the toxicity of x-radiation [12]. In this assay arthritis is induced by mycobacteria.…”

Section: Pharmacology and Toxicology Of Azimexon And Ciamexonmentioning

confidence: 96%

Chemistry and Pharmacology of Imexon and Related Cyanoaziridines

Wa¹,

Rt²

2012

CMC

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Following the demonstration that addition of a 2-cyano group to aziridines prevented DNA alkylation and thus reduced toxicity, many novel 2-cyanoaziridines were synthesized and evaluated as immunomodulating and antitumor agents. They typically reacted with thiols such as cysteine, depleting them and allowing the accumulation of reactive oxygen species. Two of these compounds, azimexon and ciamexon, showed activity against tumors in clinical trials. Imexon was produced by cyclization of 2-cyanoaziridine-1- carboxamide in the presence of hydroxide ions. The two enantiomers were prepared by a process involving chiral chromatography. They were equipotent against cultured tumor cells. Imexon also reacts with thiols and it is especially potent against multiple myeloma in cell cultures. An efficient chemical synthesis and a lyophilization formulation of imexon as a water soluble, injectible drug, were developed. In Phase I and I/II clinical trials imexon showed hints of activity against a variety of tumors, but a randomized double-blind Phase II trial of imexon plus gemcitabine versus gemcitabine alone in pancreatic cancer showed no enhancement of activity above that of gemcitabine alone. This result was disappointing because in cell culture and mice the two compounds were synergistic. Based on a complete response in a Phase I trial, a new Phase II clinical trial of imexon is underway in non-Hodgkins lymphoma.

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“…Both compounds also markedly reduce the toxicity of x-radiation [12]. In this assay arthritis is induced by mycobacteria.…”

Section: Pharmacology and Toxicology Of Azimexon And Ciamexonmentioning

confidence: 96%

Chemistry and Pharmacology of Imexon and Related Cyanoaziridines

Wa¹,

Rt²

2012

CMC

View full text Add to dashboard Cite

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Prospidine versus methotrexate pulse in highly active rheumatoid arthritis: A controlled 6-month clinical trial

Benenson

Timina

1994

Clin Rheumatol

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Twenty-seven patients with highly active, refractory rheumatoid arthritis (RA) were treated with the new anti-rheumatic drug prospidine, in view of selecting the optimum pulse regimen and comparing its short-term use with methotrexate (MTX). Prospidine was administered intravenously 500 mg every 3-5 days in the hospital and then monthly. Fifteen patients received MTX (30 mg/week intravenously in hospital and then monthly. Fifteen patients received MTX (30 mg/week intravenously in hospital and then orally 7.5-15 mg/week). The randomisation code was 2:1. We assessed 7 clinical and 4 lab data. The clinical improvement was noticed statistically after 2-4 weeks in 85% prospidine-patients and sustained up to 6 months in 73% (cp. 40% and 57% by the MTX). Only in the prospidine patients were a significant reduction of the mean daily prednisolone dose and the levels of rheumatoid factor and immune complexes observed. Prospidine and MTX had a similar incidence of side effects (39% and 43%), but all drop-outs in prospidine pulse were due to lack of response (26%) and to initial intolerance (4%). Drop-outs in MTX pulse were connected both with drug toxicity (14%) and with lack of response (7%). Alternate prospidine pulse, as highly anti-inflammatory, rapidly acting and well-tolerated regimen, may be used in treating severe forms of RA.

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