Study of TAK-935 as an Adjunctive Therapy in Adult Participants With Complex Regional Pain Syndrome (CRPS)

NCT ID: NCT03990649

Last Updated: 2021-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-23
• Study Completion Date: 2020-10-28

Brief Summary

The purpose of this study is to investigate the effect of soticlestat (TAK-935) on calculated 24-hour average pain intensity by the numeric pain scale (NPS).

Detailed Description

The drug being tested in this study is called soticlestat (TAK-935). Soticlestat is being tested to treat people with chronic complex regional pain syndrome (CRPS). This study will look at the efficacy, safety, and tolerability of soticlestat as an adjunctive therapy in participants with CRPS.

The study will enroll approximately 24 patients. Participants will be randomly assigned (by chance, like flipping a coin) in 2:1 ratio to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

Soticlestat 100 mg tablets, 100, 200 or 300 mg twice daily (BID) Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

Participants will receive 100 mg soticlestat tablets or soticlestat matching placebo tablets, BID for Week 1, 2x100 mg soticlestat tablets or soticlestat matching placebo tablets, BID for Week 2 and followed by 3x100 mg soticlestat tablets or soticlestat matching placebo tablets, BID for Week 3. Dose will be uptitrated based on safety and tolerability in titration period. Participants will continue to receive the same dose in maintenance period. Dose adjustments during maintenance period may take place due to safety and tolerability.

Participants will then enter Part B (optional) or taper period. In Part B all participants will receive soticlestat 2x100 mg tablets, BID for 1 Week, followed by soticlestat 3x100 mg tablets, BID for 1 Week. Dose will be uptitrated/downtitrated based on safety and tolerability in titration period (Part B), participants will continue to receive the same dose in maintenance period (Part B) and followed by a taper period.

This multi-center trial will be conducted in United Kingdom. The overall time to participate in this study is approximately 36 weeks. Participants will make multiple visits to the clinic and will be contacted by telephone 15 days after last dose of study drug for a follow-up assessment.

Conditions

Complex Regional Pain Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Double-Blind Treatment Period - Part A: Placebo

Soticlestat matching placebo tablets, orally, twice daily (BID) for Weeks 1, 2 and 3 in Double blind Titration Period. Soticlestat matching placebo tablets, orally BID for 12 weeks in Double blind Maintenance Period. Taper period (if participant did not continue to Part B): Dose of soticlestat matching placebo tablets was reduced to next lower dose every 3 days (maximum 6 days) until discontinuation.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Soticlestat matching placebo tablets

Double-Blind Treatment Period - Part A: Soticlestat

Soticlestat, tablet, orally, 100 mg BID for Week 1, followed by 2×100 mg tablets, soticlestat, orally BID for Week 2, further followed by 3×100 mg tablets, soticlestat, orally BID for Week 3. Dose was uptitrated every week based on safety and tolerability. Part A (Double blind Maintenance Period): 3×100 mg tablets, soticlestat, orally BID for 12 weeks. Dose was adjusted during Maintenance Period due to safety and tolerability. Taper Period (if participant did not continue to Part B): Dose of soticlestat was reduced to next lower dose every 3 days (maximum 6 days) until soticlestat was discontinued.

Group Type: EXPERIMENTAL

Soticlestat

Intervention Type: DRUG

Soticlestat tablets

Open-Label Extension Period - Part B: Soticlestat

Soticlestat, 2×100 mg tablets, orally, BID for Week 1, followed by 3×100 mg tablets, soticlestat, orally, BID for Week 2. Dose was uptitrated every week based on safety and tolerability. Part B (Open label extension: Maintenance Period): 3×100 mg tablets, soticlestat, orally, BID for 12 weeks. Dose was adjusted during Maintenance Period due to safety and tolerability. Taper Period: Dose of soticlestat was reduced to next lower dose every 3 days (maximum 6 days) until soticlestat was discontinued.

Group Type: EXPERIMENTAL

Soticlestat

Intervention Type: DRUG

Soticlestat tablets

Interventions

Soticlestat

Soticlestat tablets

Intervention Type: DRUG

Placebo

Soticlestat matching placebo tablets

Intervention Type: DRUG

Other Intervention Names

TAK-935

Eligibility Criteria

Inclusion Criteria

1. Participant meets the Budapest clinical diagnosis of complex regional pain syndrome (CRPS) at the screening visit and is at least 6 months since onset of symptoms.

2. Participant's pain medications and nondrug treatments must be stable (regimented per prescription) for 1 month prior to screening and remain stable throughout Part A.

3. Participant agrees to use a single previously prescribed rescue medication within the prescribed dose during Part A of the study and to record the daily use of these medications.

4. Participant must have an average 24-hour pain intensity score ≥4 and ≤9 on the 24-hour average pain intensity numeric pain scale (NPS) during screening/baseline. This score will be calculated by averaging the daily 24 hour pain intensity scores for the past seven days prior to randomization. The participant must have daily 24-hour pain intensity scores recorded for at least 6 of the past 7 days.

Exclusion Criteria

1. Currently receiving intravenous (IV) or oral ketamine, history of IV or oral ketamine use within the past 6 weeks prior to screening, or planned use of IV or oral ketamine during this study.

2. Participant is receiving chronic opioid treatment at a dose that has not been stable 28 days prior to screening.

3. Participant is receiving chronic opioid treatment >160 mg of morphine equivalent per day.

4. Participant has a positive drug screen for phencyclidine, amphetamine/ methamphetamine, or cocaine at screening. Cannabis is allowed..

5. Participant is positive for hepatitis B or hepatitis C infection at screening. (Note that participants who have been vaccinated against hepatitis B [hepatitis B surface antibody {Ab}-positive] who are negative for other markers of prior hepatitis B infection [eg, negative for hepatitis B core Ab] are eligible. Also, note that participants who are positive for hepatitis C Ab are eligible if they have a negative hepatitis C viral load by quantitative polymerase chain reaction).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

St Pancras Clinical Research

London, England, United Kingdom

Lancashire Teaching Hospitals NHS Foundation Trust

Preston, England, United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, England, United Kingdom

Countries

United Kingdom

References

Ratcliffe S, Arkilo D, Asgharnejad M, Bhattacharya S, Harden RN. Randomized controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in adults with complex regional pain syndrome. Pain Med. 2023 Jul 5;24(7):872-880. doi: 10.1093/pm/pnac198.

Reference Type: DERIVED

PMID: 36538782 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TAK-935-2008

Identifier Type: -

Identifier Source: org_study_id