Clinical trial NCT03990649: Study of TAK-935 as an Adjunctive Therapy in Adult Participants With Complex Regional Pain Syndrome (CRPS)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Complex Regional Pain Syndrome
Keywords: Drug Therapy
Soticlestat
TAk-935
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-06-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A
timeFrame: Baseline and Week 15
Secondary outcomes:
measure: Percent Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A
timeFrame: Baseline and Week 15
measure: Percentage of Participants Considered Responders at the End of Part A
timeFrame: Week 15
measure: Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A
timeFrame: Baseline and Week 15
measure: Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A
timeFrame: Baseline and Week 15
measure: Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A
timeFrame: Week 15
measure: Change From Baseline in Complex Regional Pain Syndrome (CSS) at the End of Part A
timeFrame: Baseline and Week 15
measure: Percent Change From Baseline in CSS at the End of Part A
timeFrame: Baseline and Week 15
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Pancras Clinical Research
state: England
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
state: England
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: England
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: