AM1476 - A Phase I, SAD-MAD Study in Healthy Volunteers
Research type
Research Study
Full title
AM1476 - A Phase I, Double-blind, Placebo-controlled, Single and Multiple Oral Dose, Safety, Tolerability, and Pharmacokinetic Study in Healthy Subjects
IRAS ID
278161
Contact name
Ashley Brooks
Contact email
Sponsor organisation
AnaMar A.B
Eudract number
2019-004800-37
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
REC Ref, 20/WA/0057
Duration of Study in the UK
0 years, 6 months, 14 days
Research summary
Research Summary
AM1476 is a 5 hydroxytryptamine receptor 2B (5 HT2B) antagonist being developed by AnaMar AB for the treatment of systemic sclerosis. Peripheral 5 HT2B receptors have been suggested to play a significant role in fibrosis, with the receptor being present in fibrotic tissues.
This is the first time AM1476 will be administered to humans. This will be a double-blind, randomised, placebo-controlled, single and multiple oral dose study conducted in 2 parts.
Part A will comprise a single dose incorporating a food effect evaluation. Overall, 48 subjects will be studied in Groups A1 to A6, with each group consisting of 8 subjects. Each subject will participate in 1 treatment period, except for Group A3, where each subject will participate in 2 treatment periods separated by a minimum of 6 days.
In each of Groups A1 to A6, subjects will receive AM1476 or placebo. All doses will be administered in the fasted state except Group A3. In Group A3, subjects will have the same treatment in two periods either in the fasted state or after a high fat breakfast such that each subject will receive 2 single doses of AM1476 or placebo during the study. Although a food effect evaluation is planned to occur in Group A3, this may be subject to change depending upon ongoing review of the PK data.
Part B will comprise a multiple dose, sequential group design. It may start following review of the safety and tolerability and PK data for Group A4. Each subject will participate in 1 treatment period only. Overall 24 subjects will take part in Part B.
In each of Groups B1 to B3, subjects will receive AM1476 or placebo once daily. The dietary state for dosing in Part B will be subject to review of the PK data from the fed/fasted comparison in Part A.
Summary of Results
CLINICAL TRIAL RESULTS SUMMARY A trial to test how different amounts of AM1476 are tolerated in healthy men and women.
THANK YOU!
Thank you to those who participated in this research study for the trial medicine (AM1476). Without trial participants, drug development would not be possible. Participation in this trial has helped the researchers learn how AM1476 works and how safe it is to use.
The trial information given in this summary is from one trial only and must not be used to make medical decisions. This drug is not yet approved, and the outcomes of this trial may not apply to all patients. Do not change your current medical treatment without consulting your doctor.
WHAT IS SYSTEMIC SCLEROSIS?
Systemic sclerosis is a common disease caused by the body's own defense system attacking the tissues in the skin and other organs of the body. Systemic sclerosis causes cells in the connective tissue to produce too much collagen, causing scarring and thickening (fibrosis) of the tissue. AM1476 is a medicine that is being tested for the treatment of systemic sclerosis.
WHAT WAS THE PURPOSE OF THIS CLINICAL TRIAL?
This trial was designed to answer this question:
How safe and well tolerated are different amounts of AM1476 in healthy people?
HOW WAS THIS TRIAL DONE?
Who took part in this trial?
This trial included 63 healthy men and 34 healthy women between the ages of 18 to 60.
Where did this trial take place?
This trial took place in the United Kingdom.
When did this trial take place?
This trial started in December 2020 and ended in December 2021.
What treatments were tested in this trial?
This trial studied different amounts of AM1476 compared to a placebo. A placebo looks and tastes like the real medicine but does not have any medical ingredients in it. AM1476 and placebo were given by mouth as capsules without food. For some people, AM1476 and placebo capsules were also given with food.
What has been completed?
The trial was split into 2 parts (Part A and Part B). In Part A, everyone took AM1476 or placebo once without food and some people also took AM1476 or placebo once with food. In Part B, people took AM1476 or placebo for 10 days without food. In each part, healthy males and females were selected to either receive AM1476 or placebo by chance (randomised) to reduce differences between the people receiving AM1476 or placebo. Reducing differences between the people receiving AM1476 or placebo makes the comparison between the groups fairer. This trial was also “double-blinded.” This means that neither the people taking part in the trial nor doctors knew who was given AM1476 or placebo. This was done to make sure that the trial results were not influenced in any way.
In both parts, the participants were split into groups. A different amount of AM1476 was tested in each group, starting at the lowest amount in the first group. After the first group had taken AM1476, the trial doctor checked for any medical issues. The trial continued and the next group took a higher amount of AM1476, only when the medicine was shown to be safe. This was done for every group. Before treatment, the trial doctor checked the health of every person to ensure they could be in the trial. During the trial, the trial doctor looked for any side effects of the AM1476.
PART A –AM1476 OR PLACEBO TAKEN ONCE
Everyone took AM1476 or placebo without food on the first day of the study and stayed at the study site until Day 3. There were 2 groups of participants who returned to the study site 6 days later to repeat the same assessments, but this time they took AM1476 or placebo with food.
Overall in Part A, 55 people took AM1476 and 18 people took placebo.
PART B –AM1476 OR PLACEBO TAKEN FOR 10 DAYS Everyone took AM1476 or placebo in the fasted state either once a day or twice a day for 10 days and stayed at the study site until Day 12.
Overall in Part B, 18 people took AM1476 and 6 people took placebo.
WHAT ARE THE MAIN RESULTS OF THIS TRIAL?
Overall, the researchers learned that:
• All amounts of AM1476 tested were found to be safe and well tolerated by the trial doctor.
• In Part A, 3 out of 18 people (17%) had medical issues after taking placebo and 24 out of 55 people (44%) had medical issues after taking AM1476.
• In Part B, 6 out of 6 people (100%) had medical issues after taking placebo and 9 out of 18 people (50%) had medical issues after taking AM1476.
• The majority of medical issues seen in people who took AM1476 in the trial were mild (85% were mild in people who took AM1476 once and 93% were mild in people who took AM1476 for 10 days) and did not need other medicine to treat them.
• Pulse rate (when measured lying down) became higher when people took AM1476 once at the highest amount tested. This did not happen at any other amounts of AM1476 after being given either once or for 10 days. Except for pulse rate, there were no important findings in other vital signs assessments such as blood pressure, breathing rate, or body temperature.
• There were no important findings in blood tests, electrical activity of the heart, physical examinations, or brain or nerve examinations when different amounts of AM1476 were given either once or for 10 days.
WHAT WERE THE SIDE EFFECTS?
In this study, some people experienced side effects. Side effects are unwanted medical events (such as a headache) that happen during the study, and which the trial doctor (investigator) thought could have been caused by the treatments in the trial. If the trial doctor (investigator) thought the medical event was not caused by the treatments in the trial then this was called a ‘medical issue’ instead. Not all the people in this trial had side effects.
None of the side effects seen in this trial were considered serious. Nor did they cause anyone to leave the trial before the end.
PART A – AM1476 OR PLACEBO TAKEN ONCE
In Part A, 1 out of 18 people (6%) had side effects from placebo. There were no side effects that were seen in 2 or more people after taking placebo. In Part A, 16 out of 55 people (29%) had side effects from AM1476. The most common side effects that were seen in 2 or more people after taking AM1476 were:
• feeling sick (10 of 55 people [18%])
• vomiting (4 of 55 people [7%])
• dizziness (4 of 55 people [7%])
• headache (2 of 55 people [4%])
• almost fainting (2 of 55 people [4%])
PART B –AM1476 OR PLACEBO TAKEN FOR 10 DAYS In Part B, 4 out of 6 people (67%) had side effects from placebo. The only side effect that was seen in 2 or more people after taking placebo was:
• headache (2 of 6 people [33%]).
In Part B, 6 out of 18 people (33%) had side effects from AM1476. The most common side effects that were seen in 2 or more people after taking AM1476 were:
• feeling sick (3 of 18 people [17%])
• headache (3 of 18 people [17%])
• muscle spasms (2 of 18 people [11%])
• forceful heartbeat that was fast or not regular (2 of 18 people [11%])
WHAT WAS LEARNED FROM THIS TRIAL?
Findings from this trial helped to decide the amount of medicine and how often it should be taken for future studies in patients.
WHERE CAN I FIND MORE INFORMATION ABOUT THIS TRIAL?
Trial Title AM1476 - A phase I, double-blind, placebo-controlled, single- and multiple-oral dose, safety, tolerability, and pharmacokinetic study in healthy subjects.
Public Trial Title A trial to test how different amounts of AM1476 are tolerated in healthy men and women.
Protocol Number 1476-291-001
Study Sponsor AnaMar AB - https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVySRXfHYla0DDUprZa16p8-3DL53I_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJLApHJzSXC4kIYbf9S10xGlevdWeiZgJAQXiwjudy0KP8gO2PaBOfnCrMevdS0UfEPT7rJEr81KO5sccWJkPKf9FXBA-2B7-2B9YmIsJ79Zy3755siR7T6RR45-2BAHHG9x-2FlrAohlDG6qjzb8MvpaWM-2BlWk-2BH-2FLdLhgzksWvje10spBCA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C3d4366f7509646d43c1e08dad7962922%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638059337177724196%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=xPPvQJ1OtnNu%2Bj01okx4kohEIM%2FWCLlHp2WaBxOYppI%3D&reserved=0
Please email any questions to info@anamar.com.
This study is also registered on https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C3d4366f7509646d43c1e08dad7962922%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638059337177724196%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=IDqR26Vfr21WHLp7WoT9uAEXsB1OK3bkkh2B4cw0Xgo%3D&reserved=0
ARE THERE PLANS FOR FURTHER TRIALS?
AnaMar AB plan to run other trials in healthy people and in patients with systemic sclerosis. It is hoped that clinical trials with AM1476 will show that this is a safe and effective medicine that can be used in the future.REC name
Wales REC 1
REC reference
20/WA/0057
Date of REC Opinion
25 Mar 2020
REC opinion
Further Information Favourable Opinion