DP13 SAD/MAD in Healthy Volunteers
Research type
Research Study
Full title
DP13 – A Phase I, Double Blind, Placebo Controlled, Single and Multiple Ascending Oral Dose, Safety, Tolerability, Pharmacodynamic, and Pharmacokinetic Study of DP13 in Healthy Male Subjects
IRAS ID
214310
Contact name
Ashley Brooks
Contact email
Sponsor organisation
DAMIAN PHARMA
Eudract number
2016-003648-36
Duration of Study in the UK
0 years, 8 months, 10 days
Research summary
Fadrozole is a well tolerated drug that was registered in Japan (under the brand name Afema) until 2007 for the treatment of oestrogen-dependent breast cancer. Fadrozole is a mixture of 2 different “enantiomers” – these are molecules that appear the same but are actually mirror images of each other (like a pair of gloves). The 2 enantiomers of fadrozole act differently within the body. One “enantiomer ” acts to inhibit the enzyme called aromatase and causes oestrogen hormone suppression. This was the desired activity of Afema. The other “enantiomer” acts to inhibit the enzyme called aldosterone-synthase and causes aldosterone hormone suppression. This was a secondary effect of Afema. Damian Pharma is developing the purified second enantiomer of fadrozole as study drug DP13 for the treatment of patients with primary hyperaldosteronism – a condition where the adrenal glands produce excessive levels of aldosterone – a hormone involved in the control of salt levels and blood pressure.
The objective of the present clinical study in healthy male volunteers is to demonstrate how DP13 is absorbed and eliminated in the blood stream and how it concomitantly lowers blood aldosterone levels. The study will also demonstrate how selectively DP13 suppresses aldosterone in comparison to other hormones such as the stress hormone cortisol and the sex hormones oestrogen and testosterone. The so achieved DP13 dose-effect profile can be indirectly compared to published studies with equivalent doses of fadrozole.
As the clinical study consists of two parts, participants will take part in either Part A or Part B. Part A will comprise a randomized, Single Ascending Dose (SAD), alternating group, 3 period study. Part B will comprise a Mutiple Ascending Dose (MAD), sequential group study. Participants will provide at selected time points blood samples to measure the DP13 drug levels and the concentrations of hormones i.e. aldosterone, cortisol, oestrogen and testosterone. In order to better show any suppression of cortisol levels by DP13, the cortisol production in the adrenal gland is briefly stimulated with administration of adrenocorticotropic hormone (ACTH - Synacthen), a naturally occurring hormone.
REC name
London - Brent Research Ethics Committee
REC reference
16/LO/1825
Date of REC Opinion
4 Jan 2017
REC opinion
Further Information Favourable Opinion