TAK-935 in Adult Subjects With Complex Regional Pain Syndrome
Research type
Research Study
Full title
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 as an Adjunctive Therapy in Adult Subjects With Chronic Complex Regional Pain Syndrome
IRAS ID
261318
Contact name
Stuart Ratcliffe
Contact email
Sponsor organisation
Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda
Eudract number
2018-004750-21
Duration of Study in the UK
1 years, 0 months, 16 days
Research summary
Research Summary
TAK-935 is an investigational medicine developed as a treatment for epilepsy that is being evaluated as a possible treatment for patients with Complex Regional Pain Syndrome (CRPS). Since the majority of CRPS patients’ symptoms resolve within the first 6 months, the large unmet need is for those patients with chronic disease.The purpose of this phase 2a study is to evaluate how well the study medicine TAK-935 works to reduce pain and improve overall function in people with CRPS. This study will also look at how safe and tolerable TAK-935 is in people with CRPS.
Approximately 24 male and female patients aged 18 to 75 from the United Kingdom will be invited to join this study.This study is divided into 2 parts. Part A is a double-blind, randomised study meaning the participant could be assigned to TAK-935 or placebo (neither the doctor or participant will know what the participant is assigned to). Part B is an optional open-label study, which means that everyone taking part will receive TAK-935.
Each participant could be involved in the study for around 36 weeks. Part A involves a screening phase of up to 28 days and treatment period of 15 weeks with 7 scheduled visits to the study centre. Part B involves a treatment period of 14 weeks with 6 scheduled visits to the study centre. After either Part A or Part B the participant will have a final treatment period of up to 6 days during which time the dose level of TAK-935 will be slowly decreased. Participants will have a follow-up telephone call 15 days after their last dose of the study medication.
Study procedures involve: physical exams, neurological exams, eye exams, vital signs, electrocardiograms, questionnaires, blood and urine tests, diary completion, dosing of medication, reviews of medications, medical history and health status.
Summary of Results
This is a summary of a clinical study of soticlestat in adults with Chronic Complex Regional Pain Syndrome (CRPS).Why was this study done?
Chronic Complex Regional Pain Syndrome, or CRPS for short, is a condition that causes long-lasting pain. The pain can occur anywhere in the body but is more common in the arms and legs. The pain usually starts after a minor injury but is more severe and continues long after the injury has healed. CRPS is difficult to treat so a new medicine called soticlestat was tested to see if it works with this condition.People with CRPS took part in this study. The study had 2 parts. In Part A, they took tablets of soticlestat or a placebo for up to 15 weeks. In this study, a placebo looked like a soticlestat tablet but had no medicine in it. In Part B, they took tablets of soticlestat for up to 14 weeks.
The main aim of the study was to learn if soticlestat could reduce pain in people with CRPS. Side effects from the medicines were also recorded.
When was this study done?
This study started in July 2019 and ended in October 2020.Who took part in this study?
Men and women from 18 to 75 years old with Chronic Complex Regional Pain Syndrome (CRPS) took part.People could not take part in the study if they were taking certain medicines to control their pain. Examples are ketamine and high doses of morphine or similar medicines.
24 people took part in this study: 7 men and 17 women aged from 18 to 62 years old. 15 people took soticlestat and 9 took the placebo.
Where was this study done?
This study took place in 3 clinics in the United Kingdom.What happened during this study?
In this study, people visited their clinic many times. At the first visit, a study doctor checked who could take part.Part A
People in the study were placed in 1 of 2 treatment groups. One group took soticlestat and the other group took the placebo. The group people were placed in was decided by chance. This was to make the results fairer when comparing study medicines or treatments.
15 people were treated with soticlestat and 9 with the placebo.
• before the treatment started and during the whole study, people in the study recorded their pain levels in a diary 3 times per day, every day. They did this using a score from 0 to 10, where 0 was no pain and 10 was unbearable pain.
• people took 100 milligrams (mg) of soticlestat (or the placebo) twice a day for 1 week.
• if they had no medical problems, the dose was increased to 200 mg soticlestat (or the placebo) twice a day for a further week.
• after this, the study doctor could increase the dose to 300 mg soticlestat twice a day (or the placebo) for the remainder of part A.
The study doctor could adjust the dose during the study if needed.Part B
After Part A, 18 people continued onto Part B for up to 14 weeks. Those who didn’t continue onto Part B were weaned off their dose. Then they visited the clinic for a final check-up about 15 days after they took their last tablet.
• people took 200 mg soticlestat twice a day for 1 week. This included 6 people who took the placebo in Part A.
• after this, the dose could be increased to 300 mg twice a day if people had no medical problems from the lower dose.
• people stayed on the same dose of soticlestat (200 mg or 300 mg) for 12 weeks.
• after 14 weeks, they were weaned off their dose. Then they visited the clinic for a final check-up about 15 days after they had taken their final tablet.Were there any side effects?
In clinical studies, side effects are medical problems thought to be caused by the study medicines or study treatments. Not everyone in this study had side effects. Some people had more than 1 side effect. Also, a side effect can happen more than once in the same person.6 people who took the placebo in Part A, switched to soticlestat in Part B. This meant that a total of 21 people took soticlestat at some point during this study.
- 13 out of 21 people (62%) had side effects from soticlestat: 19% headache; 19% feeling dizzy, 14% difficulty sleeping, 14% feel like vomiting, 10% dry mouth, 10% feeling tired, 5% feeling sluggish.
- 6 out of 9 people (67%) had side effects from placebo: 44% headache; 22% feeling dizzy , 11% difficulty sleeping, 11% feel like vomiting, 0% dry mouth, 0% feeling tired, 11 % feeling sluggishA side effect is called serious when it is life-threatening, causes lasting problems, or if hospital care is needed. Nobody had serious side effects in this study.
What were the results?
Did soticlestat reduce pain in people with CRPS?
To answer this question, the researchers worked out the average daily pain scores that people in the study had recorded before treatment and after 12 weeks of treatment during Part A. Pain was scored from 0 to 10, where 0 was no pain and 10 was unbearable pain. The average pain score was about 6 points both before and after treatment. This happened for people who took soticlestat or the placebo.
As the pain score was about the same in both groups before and after treatment, this study could not prove if soticlestat reduced pain in people with CRPS.How has this study helped patients and researchers?
Doctors check the results of many studies to decide which medicines and treatments work best for their patients and to check for side effects. This summary only shows the results of this 1 study. Other studies might have different results. So, you should not change your treatment based on the results of this 1 study without first talking to your doctor.Are there plans for further studies?
There are no further studies planned with soticlestat in people with CRPS.Where can I find out more about this study?
The full title of this study is:
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 as an Adjunctive Therapy in Adult Subjects with Chronic Complex Regional Pain SyndromeTakeda, is the sponsor of this study.
Takeda has its headquarters in Nihonbashi, Tokyo in Japan.You can find out more about this study at these websites:
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.takeda.com%2F&data=04%7C01%7Capprovals%40hra.nhs.uk%7Cfba275948cd2402df33008d9a84c1da1%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637725867129332398%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=%2Bta6%2FhUAm4JLST6dW%2FcoEus2mDsObb%2B2xOJ7eFCRQP4%3D&reserved=0
Type “TAK-935-2008” in Trial Identifier in the Filters on the left of the page.https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2Fctr-search%2Ftrial%2F2018-004750-21%2FGB&data=04%7C01%7Capprovals%40hra.nhs.uk%7Cfba275948cd2402df33008d9a84c1da1%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637725867129332398%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=mUNc%2B279PpcOUZfsw0f4qycD%2Bx%2FcsL2YnAUBSpW%2FAM0%3D&reserved=0
The EudraCT number for this study is 2018-004750-21.https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMmgE-2BYMwR3I-2FjxXOmF1t-2F6Q-3D-3DNuxm_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YI0GUEgmSRaqR7kjbI41btb05ugP5HOAnHXVAODmAMYFyWZy0iT8ne0Dii0egkNbo2ewYnt-2BjU3rQKtYhI4w1nDLoemunIqqvCAETjShs6kRhmG35eOycbMvTLymDU81hGZGQxxfoU5TAgK4McjFu7-2FalgNyA1hi00KKNa9svuMFQ-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7Cfba275948cd2402df33008d9a84c1da1%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637725867129332398%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=F3sjrOjc3ahw0%2B%2Bzj6%2Fz1iUKfR3izNnQQpE67Kce3us%3D&reserved=0
The NCT number for this study is NCT03990649.REC name
London - Chelsea Research Ethics Committee
REC reference
19/LO/0558
Date of REC Opinion
10 Jun 2019
REC opinion
Further Information Favourable Opinion