* SAD MAD Study of EVX-101 in Healthy Volunteers (QSC205766)
Research type
Research Study
Full title
A Phase 1 Single- and Multiple-Ascending Dose Study of the Safety and Pharmacokinetics of a Gastro-Retentive Formulation of 5-Hydroxytryptophan (5-HTP) and Low-Dose Carbidopa (EVX-101) in Healthy Subjects Taking Escitalopram
IRAS ID
1004711
Contact name
Dr. Jacob Jacobsen, PhD
Contact email
Sponsor organisation
Evecxia Therapeutics Inc.
Eudract number
2021-006715-28
ISRCTN Number
ISRCTN42835524
Research summary
The Sponsor is developing the test medicine, EVX-101, as a potential adjunctive treatment of depression. Adjunctive treatment is something that is given in addition to initial primary treatment e.g therapy. Depression is a common mental health problem that causes people to experience low mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy and poor concentration.\n\nThis two-part healthy volunteer study will try to identify what the body does to the test medicine (pharmacokinetics) and to assess the safety and tolerability of the test medicine, given as single and multiple doses. \n\nThis study will take place at one non-NHS site, enrolling up to 92 male and female volunteers aged between 18 to 55 years.\n\nIn order to reflect the intended clinical use of EVX-101, volunteers will receive co-treatment to stable blood levels with escitalopram (a marketed product for treatment of depression), both at outpatient visits and at home dosing, before and after test medicine/placebo dosing, for up to 28 days in Part 1 and up to 34 days in Part 2. \n\nVolunteers in Part 1 will receive a single dose of the test medicine or placebo on Day 21, which will be given as two equal administrations approx. 12 hours apart.\n\nVolunteers in Part 2 will receive multiple doses of the test medicine or placebo from Day 21 up to and including Day 27. Doses will be given as two equal administrations approx. 12 hours apart, with a final dose on the seventh day. Volunteers will receive a follow up phone call 7 to 14 days after their final escitalopram dose.\n\nVolunteer’s blood and urine will be taken throughout the study for analysis of the test medicine and for their safety. \n\nVolunteers are expected to be involved in this study for approximately 12 weeks from screening to the follow up call.
Lay summary of study results
The Sponsor for this study was Evecxia Therapeutics Inc. and the study was conducted by Quotient Sciences (a clinical research organisation) at their clinical unit in Nottingham, UK. The study took place from 15 Mar 2022 until 29 Dec 2022. We would like to take this opportunity to thank all study volunteers.
What was this study about?
The aim of this study was to find out how single and multiple doses of the test medicine, EVX-101, were taken up by the body, how well they were tolerated and how the test medicine was working in the body. Because the test medicine is intended to be used for patients already taking antidepressants, in this study the test medicine was taken along with a commonly used antidepressant called escitalopram.Who took part in this study?
There were 2 parts to this study. Different volunteers took part in each part. Volunteers were healthy males and healthy females who were not pregnant and not breastfeeding.
Part 1 had 18 volunteers aged 21 to 55 years old, and Part 2 had 20 volunteers aged 28 to 54 years old.How was this study done?
In each part, some volunteers received the test medication while other volunteers took a placebo or “dummy test medicine”, which looked like the test medicine but contained no active ingredients. Whether a volunteer received the test medicine or placebo was decided at random. All volunteers took escitalopram.
The study was double-blind, which means that volunteers did not know whether they received test medicine or placebo and the study staff did not know either. This means that the results were not affected by volunteers or study staff knowing whether the test medicine or placebo had been taken.
In Part 1, volunteers were dosed in 2 groups. The second group took a lower dose of test medicine than the first. Volunteers in both groups took escitalopram daily for 28 days and the test medicine or placebo twice on Day 21.
In Part 2, volunteers took escitalopram daily for 54 days and the test medicine or placebo twice daily from Day 21 to Day 47. Every 7 days, the dose of test medicine was increased.
Throughout both parts of the study blood samples were collected to find out the amount of test medicine in the body over time. The study staff also collected information about the volunteers’ health throughout.What were the results of this study?
In Part 1, the test medicine got into the bloodstream about 1 to 2 hours after swallowing and the highest blood levels of test medicine occurred about 6 hours after the first test medicine was swallowed.
In Part 2, the test medicine got into the bloodstream about half an hour to 2 hours after swallowing the first dose. After the test medicine had been taken for 7 days, the highest blood levels occurred between about 4 and 5 and a half hours after the first test medicine dose of the day was swallowed. After the test medicine had been taken for 7 days, the amount of test medicine in the blood was at the level thought to be helpful to treat depression.
In both parts of the study, volunteers who took higher doses of the test medicine had higher amounts of test medicine in the blood.
Volunteers in both parts had increases in the amount of cortisol, a hormone, in the blood after taking the higher doses of test medicine suggesting an increase in brain serotonin, which brain cells use to communicate with each other. Antidepressants are thought to work in part by increasing brain serotonin levels. Generally, the higher the dose, the more the cortisol in the blood went up. There was no change in the amount of cortisol in the blood after taking placebo.
The test medicine was well tolerated in the healthy volunteers at the lower doses, but was less well tolerated at the higher doses. Starting at a low dose and gradually increasing the dose in Part 2 of the study appeared to improve how well tolerated the test medicine was.Did the participants have any side effects?
Yes
In Part 1, side effects occurred in 9 out of the 13 volunteers who took the test medicine and 6 of these volunteers had side effects that may have been caused by the test medicine. None of the volunteers who took placebo had side effects. 3 volunteers had moderate side effects after taking the test medicine; all the others were mild.
In Part 2, side effects occurred in all 12 volunteers who took the test medicine and all volunteers had side effects that may have been caused by the test medicine. Side effects occurred in 5 out of the 6 volunteers who took placebo. 8 volunteers had moderate side effects after taking the test medicine; all the others were mild.
Some volunteers in both parts also had side effects that may have been caused by escitalopram.
Overall, the most common side effects thought to be caused by the test medicine were feeling sick (nausea), being sick (vomiting), feeling drowsy, diarrhoea and sweating.For more information about the study, go to www.isrctn.com and search for the ISRCTN number: ISRCTN42835524.
REC name
London - Chelsea Research Ethics Committee
REC reference
22/FT/0020
Date of REC Opinion
1 Mar 2022
REC opinion
Further Information Favourable Opinion