Case Studies
Case 1: Fluoroquinolone antibiotic and monochromator testing
Case 2: Drug and phototoxicity during phase 2 in clinical trial
Case 3: Anti-diabetic agent showing a clinically relevant photosensitisation issue
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.