Safety and PK of FOR-6219 given in SAD and MAD in female HV
Research type
Research Study
Full title
A Phase I/Ib, randomised, double-blind, placebo-controlled study in healthy postmenopausal and pre-menopausal women to investigate the safety, tolerability, food effect, pharmacokinetics of single and multiple ascending oral doses of FOR-6219 and the pharmacodynamics of multiple oral doses of FOR-6219
IRAS ID
244433
Contact name
Ulrike Lorch
Contact email
Sponsor organisation
Forendo Pharma
Eudract number
2018-001200-10
Duration of Study in the UK
0 years, 5 months, 2 days
Research summary
Summary of Research
FOR-6219 is an investigational drug under development for the treatment of endometriosis. This First-In-Human trial will be performed in healthy post-menopausal women, in two parts: (I) Single ascending dose (SAD); (II) food effect and once daily, multiple ascending doses (MAD).Up to 36 volunteers will participate in Part I. Six dose levels of FOR-6219 are planned to be evaluated within two cohorts, each consisting of three treatment periods. The treatment periods of the two cohorts will use an alternate sequence design with each cohort consisting of six volunteers. Each subject will receive a total of three doses, one in each treatment period. They will be randomised to receive two ascending doses of FOR-6219 (i.e. the second dose of FOR-6219 they receive will be higher than the first) and one dose of matching placebo. Volunteers will be admitted to the study unit on Day-1, dosed on Day 1, discharged on Day 4 and attend the unit for an outpatient visit on Day 7. The treatment periods of each cohort will be separated by a washout period of at least 5x the anticipated half-life.
In Part II, up to 48 post-menopausal female volunteers will take part in the evaluation of the effect of food on drug metabolism as well as multiple ascending doses. Three dose levels of FOR-6219 are planned to be evaluated in three cohorts of eight volunteers. At each dose level, six subjects will receive the active drug, FOR-6219 and two volunteers will receive matching placebo (3:1 ratio). Volunteers will be admitted to the study unit on Day -1 and will receive a single dose of FOR-6219 on Day 1 (after a meal) and Days 3-10 (in fasted state). They will be discharged from the unit on Day 13 and attend an outpatient visit on Day 17.
Summary of Results
Endometriosis is a chronic and often debilitating disease that affects up to 10% of women of reproductive age. The main clinical symptoms of endometriosis are chronic pelvic pain, menstrual pain and pain during intercourse and up to 50% of women with endometriosis have infertility.
Overall, the study drug FOR-6219 was well tolerated at all dose levels in all three study parts. No subjects were withdrawn from the study due to treatment emergent adverse effect (TEAE). A TEAE is defined as an event that first appears during treatment, which was absent before or which worsens relative to the pre-treatment state. There were no serious adverse event (SAEs) or deaths reported. The Pharmacokinetic (PK) of FOR-6219 following a single dose and following multiple once daily or twice daily dosing was consistent. There were the two main breakdown products, FOR-6287 and FOR-1011. There was no major food effect observed on the single dose (PK) of FOR-6219 and its metabolite FOR-6287. The study suggested that FOR-6219 and FOR-1011 were absorbed into the endometrial tissue compartment determined by endometrial biopsies. Exploratory pharmacodynamic endpoints evaluated in the study indicated that FOR-6219 did not show any difference at any dose level when compared to placebo group except for normalised 4β-hydroxycholesterol plasma concentration that displayed a slight dose related increase in highest dose group compared to the other dose levels and the placebo.REC name
London - London Bridge Research Ethics Committee
REC reference
18/LO/0549
Date of REC Opinion
9 May 2018
REC opinion
Favourable Opinion