Effect of Fluvoxamine and smoking on the PK of QD AZD4635 PO in HV
Research type
Research Study
Full title
A Phase I, Open-label, Non-randomised Study to Assess the Effect of Fluvoxamine (CYP1A2 Inhibitor) and Smoking (CYP1A2 Inducer) on the Pharmacokinetics of a Single Oral Dosing of AZD4635 in Healthy Volunteers
IRAS ID
282601
Contact name
Pablo Forte Soto
Contact email
Sponsor organisation
Astra Zeneca AB
Eudract number
2020-000959-13
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 2 months, 9 days
Research summary
This is a Phase I, open-label, non-randomized, 2-period, fixed-sequence study in healthy volunteers who are either smokers or non-smokers, with a primary objective to assess the effect of CYP1A2 inhibition (treatment with fluvoxamine) and smoking (CYP1A2 inducer).
This study will be conducted in healthy subjects rather than the target patient population (ie, patients with the disease), as the PK data from healthy subjects is likely to be less variable than from the target patient population, and thus allow a better assessment of the PK effects of smoking and fluvoxamine on the PK of AZD4635. In addition, safety and tolerability data will not be biased by comorbidities.
This study is the second healthy volunteer study in the AZD4635 clinical development
programme. The Phase 1 open-label Study D8730C00002 to assess the PK and relative
bioavailability of AZD4635, comparing the performance of the solid oral capsule formulation (50 mg of AZD4635) to the existing nano-suspension in 21 non-smoking healthy male subjects is now complete. No safety concerns and no clinically significant events were observed in this study, and the 50 mg oral capsule dose of AZD4635 was well tolerated by the healthy volunteers.
As the primary objective is PK, the study is open-label. The study will include adult men and women of non-childbearing potential of 18 to 55 years of age (inclusive at screening).
Twenty-eight (28) subjects are planned to be recruited, 14 subjects who are smokers and 14 subjects who are non-smokers will be enrolled in this study in order to ensure that at least 12 completed subjects for each group are evaluable in this study.
In this study, subjects will remain resident at the Clinical Unit from admission throughout the duration of the 2 treatment periods.REC name
London - Brent Research Ethics Committee
REC reference
20/LO/0712
Date of REC Opinion
29 May 2020
REC opinion
Favourable Opinion