Advertisement

Clinical Trials of Suspension Drug Products

  • G. Michael Wall
  • Terry K. Wiernas
Chapter

Abstract

Clinical trials of a pharmaceutical product, regardless of the pharmaceutical form, are generally required by the regulatory agencies around the world as the basis for proof of safety and efficacy in the drug product approval process. Such clinical trials must be conducted in an ethical manner according to a protocol. Some of the most important aspects of clinical trials specific to suspension drug products are concerned with the clinical supplies. Blinding is particularly difficult for suspension drug products since many approved comparators are not suspensions, thus making it very challenging to mask the investigational suspension versus its comparators. Appropriate choices for globally acceptable clinical study design of suspension drug products are discussed.

Keywords

Drug Product Content Uniformity Investigational Product Clinical Supply Independent Ethic Committee 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. CFR314.126: Code of Federal Regulations Title 21, Volume 5, Food and drugs, Chapter I – Food and Drug Administration, Dept. Health and Human Services, Subchapter D-Drugs for Human Use, Part 314.126, Adequate and well-controlled studies, 2008, available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=314.126, accessed June 2, 2009.
  2. CFR56: Code of Federal Regulations Title 21, Food and drugs, Chapter I – Food and Drug Administration, Dept. Health and Human Services, Subchapter A, General Part 56 Institutional review boards, 2008, available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=56&showFR=1, accessed 1 June 2009.
  3. CFR50: Code of Federal Regulations Title 21, Food and drugs, Chapter I – Food and Drug Administration, Dept. Health and Human Services, Subchapter A, General Part 50 Protection of Human Subjects, 2008, available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=50, accessed 1 June 2009.
  4. Chin, R. and Lee, B. Y. 2008. Principles and Practice of Clinical Trial Medicine. Oxford, UK: Elsevier, Inc.Google Scholar
  5. ClinicalTrials.gov available at: http://clinicaltrials.gov/, accessed March 26, 2009.
  6. Dohar, J., Giles, W., Roland, P., Bikhazi, N., Carroll, S., Moe, R., Reese, B., Dupre, S., Wall, M., Stroman, D., McLean, C., Crenshaw, K. 2006. Topical ciprofloxacin/dexamethasone superior to oral amoxicillin/clavulanic acid in acute otitis media with otorrhea through tympanostomy tubes. Pediatrics 118(3):e1–e9.CrossRefGoogle Scholar
  7. Draft Guidance for Industry, Allergic rhinitis: clinical development programs for drug products, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research, 2000, available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071293.pdf, accessed May 25, 2009.
  8. Draft Guidance on Ketoconazole Shampoo, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research, 2008, available at: http://www.fda.gov/cder/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm08272.pdf, accessed Sept. 25, 2009.
  9. European Medicines Agency (EMEA) available at: http://www.emea.europa.eu/, accessed May 26, 2009.
  10. Friedman, L. M., Furburg, C. D., DeMets, D. L. 1998. Fundamentals of Clinical Trials. New York: Springer Science + Media LLC.Google Scholar
  11. Grady, J. O. and Linet, O. I. 1990. Early Phase Drug Evaluation in Man. Boca Raton: CRC Press.Google Scholar
  12. Guidance for Industry, Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products, U.S. Dept. Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, available at: http://www.fda.gov/cder/guidance/1397fnl.pdf, accessed May 25, 2009.
  13. Guidance for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products, U.S. Dept. Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, 2008, available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078749.pdf, accessed May 26, 2009.
  14. Guidance for Industry, Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products – Chemistry, Manufacturing, and Controls Documentation, U.S. Dept. Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, 2002, available at: http://www.fda.gov/cder/guidance/4234fnl.htm#P672_98417, accessed May 26, 2009.
  15. Guidance for Industry: Chronic Cutaneous Ulcer and Burn Wounds – Developing Products for Treatment, U.S. Dept. Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, 5600 Fishers Lane, Rockville, MD, 2006, available at: http://www.fda.gov/cber/gdlns/ulcburn.pdf, accessed May 26, 2009.
  16. Guidance for Industry Acute Bacterial Otitis Media: Developing Drugs for Treatment, Draft Guidance, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research, 2008, available at: http://www.fda.gov/cder/guidance/3892dft.pdf, accessed May 25, 2009.
  17. Draft Guidance on Ketoconazole Shampoo, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research, 2008, available at: http://www.fda.gov/cder/guidance/bioequivalence/recommendations/Ketoconazole_Sham_%2019927_RC7-08.pdf, accessed May 25, 2009.
  18. ICH Guideline for Good Clinical Practice E6 R1, 1996, available at: http://www.ich.org/LOB/media/MEDIA482.pdf, accessed june 1, 2009.
  19. ICH Note for Guidance on Non-clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals, CPMP/ICH/286/95, 2008, available at: http://www.emea.europa.eu/pdfs/human/ich/028695endraft.pdf, accessed May 25, 2009.
  20. International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. available at: http://www.ich.org/cache/compo/276-254-1.html, accessed May 26, 2009.
  21. Japan Pharmaceutical and Medical Devices Evaluation Center (PMDEC) available at: http://www.nihs.go.jp/pmdec/outline.htm, accessed May 26, 2009.
  22. Kim, K., Quesada, J., Wingertzahn, M. A., Szmaydy-Rikken, N., Darken, P., Shah, T. 2007. Coadministration of intranasal ciclesonide and inhaled fluticasone propionate-salmeterol in perennial allergic rhinitis (PAR). J Allergy Clin Immunol 119(1, Supplement 1):S143.Google Scholar
  23. Knight, P. A. and Lucken, R. N. 1977. Experience with the quality control testing of C. parvum suspension for clinical trial. Dev Biol Stand 38:51–58.PubMedGoogle Scholar
  24. Lanier, B. Q., Abelson, M. B., Berger, W. E., Granet, D. B., D’Arienzo, P. A., Spangler, D. L., Kägi, M. K. 2002. Comparison of the efficacy of combined fluticasone propionate and olopatadine versus combined fluticasone propionate and fexofenadine for the treatment of allergic rhinoconjunctivitis induced by conjunctival allergen challenge. Clin Ther 24(7):1161–1174.CrossRefPubMedGoogle Scholar
  25. Machin, D., Day, S., Green, S. Eds. 2006. Textbook of Clinical Trials. West Sussex, England: Wiley.Google Scholar
  26. Manni, G., Denis, P., Chew, P. et al. 2009. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 1%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. J Glaucoma 18(4):293–300.Google Scholar
  27. Meinert, C.L. and Tonascia, S. 1986. Clinical Trials Design, Conduct and Analysis. New York: Oxford University Press.Google Scholar
  28. Monkhouse, D. C. and Rhodes, C. T., Eds.1998. Drug Products for Clinical Trials: An International Guide to Formulation, Production, Quality Control. New York: Marcel Dekker, Inc.Google Scholar
  29. Patel, D., Garadi R., Brubaker, M., Conroy, P., Kaji, Y., Crenshaw, K., Whitling, A., Wall, G. M. 2007. Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: olopatadine hydrochloride versus mometasone furoate monohydrate. Allergy Asthma Proc 28:592–599.Google Scholar
  30. Pichichero, M. E., Casey, J. R., Block, S. L., Guttendorf, R., Flanner, H., Markowitz, D., Clausen, S. 2008. Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsilllopharyngitis due to Streptococcus pyogenes in children. Antimicrob Agents Chemother 52(7):2512–2520.CrossRefPubMedGoogle Scholar
  31. Pocock, S. J. 1983. Clinical Trials, a Practical Approach. New York: Wiley.Google Scholar
  32. Rasmussen, M. H., Andersen, R., Breum, L., Gotzsche, P. C., Hilsted, J. 1993. Cimetidine suspension as adjuvant to energy restricted diet in treating obesity. BMJ 306(6885):1093–1096.Google Scholar
  33. Roland, P. S., Anon, J. B., Moe, R. D., Conroy, P. J., Wall, G. M., Dupre, S. J., Krueger, K. A., Potts, S., Hogg, G., Stroman, D. W. 2003. Topical ciprofloxacin/dexamethasone is superior to ciprofloxacin alone in pediatric patients with acute otitis media and otorrhea through tympanostomy tubes. Laryngoscope 113(12):2116–2122.CrossRefPubMedGoogle Scholar
  34. Roland, P. S., Belcher, B. P., Bettis, R., Makabale, R. L., Conroy, P. J., Wall, G. M., Dupre, S., Potts, S., Hogg, G., Weber, K., The CiproHC Study Group. 2008. A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa. Am J Otolaryngol Head Neck Med Surg 29(4):255–261.Google Scholar
  35. Roland, P. S., Kreisler, L.S., Reese, B., Anon, J. B., Lanier, B., Conroy, P. J., Wall, G. M., Dupre, S. J., Potts, S., Hogg, G., Stroman, D. W. 2004b. Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes. Pediatrics 113(1):e40–e46.CrossRefPubMedGoogle Scholar
  36. Roland, P. S., Pien, F. D., Schultz, C. C., Henry, D. C., Conroy, P. J., Wall, G. M., Garadi, R., Dupre, S. J., Potts, S. L., Hogg, L. G., Stroman, D. W. 2004a. Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/hydrocortisone for otitis externa. Curr Med Res Opin 20(8):1175–1183.CrossRefPubMedGoogle Scholar
  37. Roland, P. S., Younis, R., Wall, G. M. 2007. A comparison of ciprofloxacin/dexamethasone with neomycin/polymyxin/hydrocortisone for otitis externa pain. Adv Ther 24(3):671–675.CrossRefPubMedGoogle Scholar
  38. Saez-Llorens, X., Rodriguez, A., Arguedas, A., Hamed, K. A., Yang, J., Pierce, P., Echols, R. 2005. Randomized, investigator-blinded, multicenter study of gatifloxacin versus amoxicillin/clavulanate treatment of recurrent and nonresponsive otitis media in children. Pediatr Infect Dis J 24(4):293–300.CrossRefPubMedGoogle Scholar
  39. Sjoqvist, R., Graffner, C., Ekham, I., Sinclair, W., Woods, J. P. 1993. In vivo validation of the release rate and palatability of remoxipride-modified release suspension. Pharm Res 10(7):1020–1026.CrossRefPubMedGoogle Scholar
  40. Steele, R. W., Estrada, B., Begue, R. E., Mirza, A., Travillion, D. A., Thomas, M. P. A. 1997. Double-blind taste comparison of pediatric antibiotic suspensions. Clinical Pediatrics 36(4):193–199.CrossRefPubMedGoogle Scholar
  41. Sweetman, S. C, Ed. 2009. Martindale: The Complete Drug Reference 36. London: Pharmaceutical Press.Google Scholar
  42. United States Food and Drug Administration (FDA) available at: http://www.fda.gov/, accessed May 26, 2009.
  43. World Medical Association Declaration of Helsinki, Ethical principles for Medical Research Involving Human Subjects, 2008, available at: http://www.wma.net/e/policy/pdf/17c.pdf, accessed June 1, 2009.

Copyright information

© AAPS 2010

Authors and Affiliations

  1. 1.Alcon Research, LtdFort WorthUSA

Personalised recommendations