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

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

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).

Study Overview

• Status: Completed
• Conditions: Complex Regional Pain Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Soticlestat

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, WC1X 8QD
      • St Pancras Clinical Research
    • Preston, England, United Kingdom, PR2 9HT
      • Lancashire Teaching Hospitals NHS Foundation Trust
    • Southampton, England, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Soticlestat matching placebo tablets
Experimental: 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.	Drug: Soticlestat; Soticlestat tablets; Other Names: TAK-935
Experimental: 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.	Drug: Soticlestat; Soticlestat tablets; Other Names: TAK-935

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A	The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. Negative change from Baseline indicated improvement.	Baseline and Week 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Mean 24-Hour Pain Intensity as Assessed by NPS Score to the End of Part A	The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable. Negative percent change from Baseline indicated improvement.	Baseline and Week 15
Percentage of Participants Considered Responders at the End of Part A	Response was defined as ≥ 30% improvement on the 24-hour pain intensity as assessed by the NPS score. The 24-hour average pain intensity was calculated from current pain intensity scores collected three times a day as measured by the electronic pain diary daily using NPS during Part A. NPS is an 11-point scale, where scores range from 0-10, 0= no pain to 10 = most pain imaginable.	Week 15
Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A	PROMIS-29 (v2.1) is a health-related quality of life survey assessing 7 domains with 4 questions on a 5-point Likert scale. Total raw domain scores are converted into T-scores from a reference population: Depression: 1=never to 5=always, T-scores:41.0-79.4; Physical function: 1=unable to do to 5=without any difficulty, T-scores: 22.5-57.0; Anxiety: 1=never to 5=always, T-scores: 40.3-81.6; Pain interference: 1=not at all to 5=very much, T-scores: 41.6-75.6; Fatigue: 1=not at all to 5=very much, T-scores: 33.7-75.8; Sleep disturbance: 1=very much to 5=not at all, T-scores: 32.0-73.3; Ability to participate in social roles or activities: 1=always to 5=never, T-scores: 27.5-64.2. High scores signify more of domain being measured. Thus, on symptom-oriented domains, higher scores=worse symptomatology and a negative change from Baseline indicates improvement. On function-oriented domains, higher score=better functioning and a positive change from Baseline indicates improvement.	Baseline and Week 15
Percent Change From Baseline in Domain Score of PROMIS-29 Version 2.1 at the End of Part A	PROMIS-29 (v2.1) is a health-related quality of life survey assessing 7 domains with 4 questions on a 5-point Likert scale. Total raw domain scores are converted into T-scores from a reference population: Depression: 1=never to 5=always, T-scores:41.0-79.4; Physical function: 1=unable to do to 5=without any difficulty, T-scores: 22.5-57.0; Anxiety: 1=never to 5=always, T-scores: 40.3-81.6; Pain interference: 1=not at all to 5=very much, T-scores: 41.6-75.6; Fatigue: 1=not at all to 5=very much, T-scores: 33.7-75.8; Sleep disturbance: 1=very much to 5=not at all, T-scores: 32.0-73.3; Ability to participate in social roles or activities: 1=always to 5=never, T-scores: 27.5-64.2. High scores signify more of domain being measured. Thus, on symptom-oriented domains, higher scores=worse symptomatology and a negative change from Baseline indicates improvement. On function-oriented domains, higher score=better functioning and a positive change from Baseline indicates improvement.	Baseline and Week 15
Percentage of Participants in Each Category of the Patient Global Impression of Change (PGIC) Scale at the End of Part A	The PGIC is a 7-point Likert scale to address the following question: Since beginning treatment at this clinic would you describe any changes (if any) in activity, limitations, symptoms, emotions and overall quality of life related to your painful condition compared to before treatment? Participants select from scale range of 1-7: very much improved (1); much improved (2); minimally improved (3); no change (4); minimally worse (5); much worse (6); very much worse (7). Only categories with at least 1 participant were reported.	Week 15
Change From Baseline in Complex Regional Pain Syndrome (CSS) at the End of Part A	Signs and symptoms reflecting the sensory, vasomotor, sudomotor/edema, and motor/trophic disturbances of CRPS had been incorporated into a clinically feasible CSS. Total CSS is a 16-point score which was calculated by the number of "yes" answers to the questions on the 8 symptoms and 8 signs when all 16 questions were answered. Negative change from Baseline indicates improvement.	Baseline and Week 15
Percent Change From Baseline in CSS at the End of Part A	Signs and symptoms reflecting the sensory, vasomotor, sudomotor/edema, and motor/trophic disturbances of CRPS had been incorporated into a clinically feasible CSS. Total CSS is a 16-point score which was calculated by the number of "yes" answers to the questions on the 8 symptoms and 8 signs when all 16 questions were answered. Negative percent change from Baseline indicates improvement.	Baseline and Week 15

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): June 29, 2020
• Study Completion (Actual): October 28, 2020

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: June 17, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: June 24, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy; Soticlestat; TAk-935
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Somatoform Disorders
• Other Study ID Numbers: TAK-935-2008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No