Case Studies

Case 1: Fluoroquinolone antibiotic and monochromator testing

Background Information

  • The drug absorbs in UVB and UVA spectrum
  • In vitro study, (3T3) neutral red uptake phototoxic assay showed positive results
  • Phototoxicity study on healthy volunteers was conducted not using a Spectratox study method but elsewhere using a solar simulator alone and the results were reported as negative
  • This study, which also included ciprofloxacin as an intended positive control, showed negative results, probably due to suboptimal light source choice and dosimetry. This (negative results with a positive control) should probably have cast uncertainty on whether the negative results with the test drug were “true negative”.
  • During launch in spring: 300 severe phototoxicity events were reported over 4 months and 20 subjects required hospitalisation

Conclusion

  • Clinically serious phototoxicity could have been detected using a Spectratox study method using monochromator testing, so avoiding patient injury

Case 2: Drug and phototoxicity during phase 2 in clinical trial

Background information

  • The investigated drug absorbs in UVB and UVA range
  • In vitro study, (3T3) neutral red uptake phototoxic assay showed positive results
  • No animal phototoxicity study was conducted
  • In the Phase 2 clinical trial phase 2, 6/200 subjects developed skin photosensitivity during the summer months

First study proposed

  • Single dose phototoxic ‘look-see’ type study gave negative results

Full regulatory study (requested after the photostudy)

  • Phototoxicity study in which placebo vs ciprofloxacin (positive control known to cause delayed phototoxicity) vs higher dose of drug were compared

Results

  • Placebo and ciprofloxacin were negative for immediate erythema
  • Ciprofloxacin was positive for delayed erythema (so confirming the ability of the study design to detect drug phototoxicity)
  • Drug in question is negative

Conclusion

  • No reproducible phototoxicity (as opposed to a rare idiosyncratic phenomenon, whereby accounting for the clinical phase 2 study finding) with the test drug.

Case 3: Anti-diabetic agent showing a clinically relevant photosensitisation issue

Background information

  • The drug absorbs in UVA
  • In vitro study, (3T3) neutral red uptake phototoxic assay showed positive results

Full regulatory study proposed

  • In vivo human volunteer regulatory type study was conducted

Results

  • The clinical trial was abandoned after 3 subjects show a Phototoxic Index (PI) >10 within the UVA region

Conclusion

  • The drug caused clinically relevant severe phototoxicity and knowing this informed further decisions about this drug.