Abstract
Phase 1 trials are an important step in drug development and are usually the first that involve human participants. Their main objective is most often to determine a safe and effective dose range for further clinical development of the drug. Specific guidelines and regulations apply to these type of trials and have been laid down by health authorities. These guidelines are aimed at minimizing the risks and maximizing the benefits and concern the trial’s objective, design, methodology, and organization. To obtain approval for a clinical trial, a Clinical Trial Application, outlining how these guidelines are implemented, has to be reviewed and approved by competent authorities and an ethical committee.
In this chapter, an overview is given of the unique features of phase 1 trials, and the specific guidelines that apply to setting up, submitting, and conducting phase 1 trials in the European Union.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Derhaschnig U, Jilma B (2010) Phase-I studies and first-in-human trials. In: Müller M (ed) Clinical pharmacology: current topics and case studies. Springer, Vienna, pp 89–99
Dixon JR (1999) The international conference on harmonization good clinical practice guideline. Qual Assur 6(2):65–74
Dunnington K, Benrimoh N, Brandquist C, Cardillo-Marricco N, Di Spirito M, Grenier J (2018) Application of pharmacokinetics in early drug development. In: Pharmacokinetics and adverse effects of drugs-mechanisms and risks factors. IntechOpen
European Commission (2003) Commission Directive 2003/94/EC laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:262:0022:0026:en:PDF. Accessed 16 April 2020
European Commission (n.d.) European Union Drug Regulating Authorities Clinical Trials Database. https://eudract.ema.europa.eu/. Accessed 6 April 2020
European Medicines Agency (1998a) ICH E9 statistical principles for clinical trials (CPMP/ICH/363/96). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002928.pdf. Accessed 6 April 2020
European Medicines Agency (1998b) ICH Topic E 8 General Considerations for Clinical Trials. Note for guidance on general considerations for clinical trials (CPMP/ICH/291/95). https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-8-general-considerations-clinical-trials-step-5_en.pdf. Accessed 1 May 2020
European Medicines Agency (2005) Guideline on data monitoring committees EMEA/CHMP/EWP/5872/03 Corr. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-data-monitoring-committees_en.pdf. Accessed 5 May 2020
European Medicines Agency (2017) Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products (EMEA/CHMP/SWP/28367/07 Rev. 1). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-strategies-identify-mitigate-risks-first-human-early-clinical-trials-investigational_en.pdf. Accessed 15 April 2020
European Medicines Agency (n.d.) National competent authorities (human). https://www.ema.europa.eu/en/partners-networks/eu-partners/eu-member-states/national-competent-authorities-human. Accessed 4 May 2020
European Monitoring Centre for Drugs and Drug Addiction and Eurojust (2016) New psychoactive substances in Europe: legislation and prosecution — current challenges and solutions, EMCDDA–Eurojust joint publication. Publications Office of the European Union, Luxembourg
European Parliament and Council of the European Union (2001) Directive 2001/20/EC of the European parliament and of the council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/dir_2001_20/dir_2001_20_en.pdf. Accessed 4 May 2020
Friedman LM, Furberg C, DeMets DL, Reboussin DM, Granger CB (2010) Fundamentals of clinical trials, vol 4. Springer, New York
Gouveia BG, Rijo P, Gonçalo TS, Reis CP (2015) Good manufacturing practices for medicinal products for human use. J Pharm Bioallied Sci 7(2):87. https://doi.org/10.4103/0975-7406.154424
Logan BK, Mohr ALA, Friscia M, Krotulski AJ, Papsun DM, Kacinko SL, Ropero-Miller JD, Huestis MA (2017) Reports of adverse events associated with use of novel psychoactive substances, 2013–2016: a review. J Anal Toxicol 41(7):573–610. https://doi.org/10.1093/jat/bkx031
Norfleet, E., & Cox Gad, S. (2010). Phase I clinical trials. Pharmaceutical Sciences Encyclopedia: Drug Discovery, Development, and Manufacturing, 1–10
Official Journal of the European Union (2014) Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials in medicinal products for human use and repealing Directive 2001/20/EC. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/reg_2014_536/reg_2014_536_en.pdf. Accessed 6 April 2020
Pacey S, Workman P, Sarker D (2011) Pharmacokinetics and pharmacodynamics in drug development. In: Encyclopedia of cancer. Springer, Berlin Heidelberg, pp 2845–2848
Shen J, Swift B, Mamelok R, Pine S, Sinclair J, Attar M (2019) Design and conduct considerations for first-in-human trials. Clin Transl Sci 12(1):6–19. https://doi.org/10.1111/cts.12582
The Association of the British Pharmaceutical Industry (2018) Guidelines for Phase I clinical trials. 2018 edition. https://www.abpi.org.uk/media/4992/guidelines-for-phase-i-clinical-trials-2018-edition-20180626.pdf. Accessed 13 March 2020
Theunissen EL, Hutten NR, Mason NL, Toennes SW, Kuypers KP, Sousa Fernandes Perna EB, Ramaekers JG (2018) Neurocognition and subjective experience following acute doses of the synthetic cannabinoid JWH-018: a phase 1, placebo-controlled, pilot study. Br J Pharmacol 175(1):18–28
Thomas DW, Burns J, Audette J, Carroll A, Dow-Hygelund C, Hay M (2016) Clinical development success rates 2006–2015. https://www.bio.org/sites/default/files/legacy/bioorg/docs/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf. Accessed 6 May 2020
Wood LF (2009) Investigational medicinal products dossier. In: Targeted regulatory writing techniques: clinical documents for drugs and biologics. Springer, Basel, pp 121–124
Wood DM, Dargan PI (2012) Novel psychoactive substances: how to understand the acute toxicity associated with the use of these substances. Ther Drug Monit 34(4):363–367. https://doi.org/10.1097/FTD.0b013e31825b954b
World Medical Association (2001) World medical association declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull World Health Organ 79(4):373
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Theunissen, E. (2021). Phase 1 Clinical Trials in Psychopharmacology. In: Schreiber, R. (eds) Modern CNS Drug Discovery . Springer, Cham. https://doi.org/10.1007/978-3-030-62351-7_16
Download citation
DOI: https://doi.org/10.1007/978-3-030-62351-7_16
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-62350-0
Online ISBN: 978-3-030-62351-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)