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

Browse trials for

• Complex Regional Pain Syndromes 196

Keywords

• Drug Therapy
• Soticlestat
• TAk-935

Study arms

• 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

• 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

• 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

Interventions

• DrugSoticlestat

  Soticlestat tablets

  Also known as: TAK-935

• DrugPlacebo

  Soticlestat matching placebo tablets

Primary outcomes

1. 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.

   Time frame: Baseline and Week 15

Secondary outcomes

1. 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.

   Time frame: Baseline and Week 15

2. 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.

   Time frame: Week 15

3. 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.

   Time frame: Baseline and Week 15

4. 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.

   Time frame: Baseline and Week 15

5. 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.

   Time frame: Week 15

6. 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.

   Time frame: Baseline and Week 15

7. 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.

   Time frame: Baseline and Week 15

Baseline characteristics

Publications

• 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. PubMed 36538782 ↗

Study documents

• Study protocol · Dec 16, 2019
• Statistical analysis plan · Feb 10, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Icf, Csr