CREATE-1: A Study to Assess the Efficacy and Safety of AXS-02 in Patients With CRPS-1 (CREATE-1)

• ClinicalTrials.gov Identifier: NCT02504008
• Recruitment Status: Active, not recruiting
• First Posted: July 21, 2015
• Last Update Posted: March 23, 2018
• Sponsor: Axsome Therapeutics, Inc.
• Information provided by (Responsible Party): Axsome Therapeutics, Inc.

Tracking Information

• First Submitted Date: July 20, 2015
• First Posted Date: July 21, 2015
• Last Update Posted Date: March 23, 2018
• Actual Study Start Date: July 2015
• Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2015)

Change in patient reported pain intensity [ Time Frame: Baseline to Week 12 ]

Patient reported pain intensity is recorded as an average daily pain intensity using an 11-point scale (0 = no pain to 10 = worst pain possible).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 21, 2018)

• Change in Brief Pain Inventory (BPI) Pain Score [ Time Frame: Baseline to Week 12 ]
  The BPI is a nine-question survey completed by the patient that assesses quality of life and health status. BPI scores range from 0 to 10, with higher values indicating greater pain.
• Patients' Global Impression of Change (PGI-C) [ Time Frame: Baseline to Week 12 ]
  The PGI-C is a patient/patient's caregiver rated scale to assess the patients overall treatment response. PGI-C is a 7-point (1-7) scale rated as; very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
• Clinicians' Global Impression of Change (CGI-C) [ Time Frame: Baseline to Week 12 ]
  The CGI-C is an investigator-rated scale to assess the overall treatment response. CGI-C is a 7-point (1-7) scale rated as; very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
• Change in EuroQOL 5-dimensions questionnaire (EQ-5D) [ Time Frame: Baseline to Week 12 ]
  The EQ-5D descriptive system comprised the following 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated by the patient at one of 5 levels, with level 1 indicating the best health state (no problems) and level 5 indicating worst health state (e.g., unable to walk about).
• Change in Short-Form McGill Pain Questionnaire (SF-MPQ-2) [ Time Frame: Baseline to Week 12 ]
  The SF-MPQ-2 measures both neuropathic and nonneuropathic pain. It contains a total of 22 descriptors, which are rated on an intensity scale of 0 = None, to 10 = Worst Possible.
• Change in bone turnover markers [ Time Frame: Baseline to Week 52 ]
  Bone turnover is measured from 2 biomarkers collected from peripheral blood samples: serum carboxy terminal telopeptide of collagen type I (CTX) and serum procollagen type I N terminal propeptide (s-P1NP).

Original Secondary Outcome Measures (submitted: July 20, 2015)

• Change in Brief Pain Inventory (BPI) Pain Score [ Time Frame: Baseline to Week 12 ]
  The BPI is a nine-question survey completed by the patient that assesses quality of life and health status. BPI scores range from 0 to 10, with higher values indicating greater pain.
• Patients' Global Impression of Change (PGI-C) [ Time Frame: Baseline to Week 12 ]
  The PGI-C is a patient/patient's caregiver rated scale to assess the patients overall treatment response. PGI-C is a 7-point (1-7) scale rated as; very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
• Clinicians' Global Impression of Change (CGI-C) [ Time Frame: Baseline to Week 12 ]
  The CGI-C is an investigator-rated scale to assess the overall treatment response. CGI-C is a 7-point (1-7) scale rated as; very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
• Change in EuroQOL 5-dimensions questionnaire (EQ-5D) [ Time Frame: Baseline to Week 12 ]
  The EQ-5D descriptive system comprised the following 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated by the patient at one of 5 levels, with level 1 indicating the best health state (no problems) and level 5 indicating worst health state (e.g., unable to walk about).
• Change in Short-Form McGill Pain Questionnaire (SF-MPQ-2) [ Time Frame: Baseline to Week 12 ]
  The SF-MPQ-2 measures both neuropathic and nonneuropathic pain. It contains a total of 22 descriptors, which are rated on an intensity scale of 0 = None, to 10 = Worst Possible.
• Change in bone turnover markers [ Time Frame: Baseline to Week 12 ]
  Bone turnover is measured from 2 biomarkers collected from peripheral blood samples: serum carboxy terminal telopeptide of collagen type I (CTX) and serum procollagen type I N terminal propeptide (s-P1NP).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CREATE-1: A Study to Assess the Efficacy and Safety of AXS-02 in Patients With CRPS-1
• Official Title: CREATE-1 Study: CRPS Treatment Evaluation 1 Study. A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of AXS-02 (Oral Zoledronate) Administered Orally to Subjects With Complex Regional Pain Syndrome Type I (CRPS-I)
• Brief Summary: This is a randomized, double-blind, placebo-controlled, 24-week study to evaluate the efficacy and safety of AXS-02 in patients with CRPS-I.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Complex Regional Pain Syndrome
• Reflex Sympathetic Dystrophy

Intervention

• Drug: AXS-02 (oral zoledronate)
  Once weekly for 6 weeks
• Drug: Placebo
  Once weekly for 6 weeks

Study Arms

• Experimental: AXS-02 (oral zoledronate)
  Administered orally in the morning on Days 1, 8, 15, 22, 29, and 36
  Intervention: Drug: AXS-02 (oral zoledronate)
• Placebo Comparator: Placebo
  Administered orally in the morning on Day 1, 8, 15, 22, 29, and 36
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 20, 2015): 190
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2019
• Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Male or female of at least 18 years of age
• Recently confirmed diagnosis of CRPS-1 (Budapest criteria)
• Average pain intensity score of ≥ 5 (based on an 11-point scale [0 - 10])
• Willing and able to provide written informed consent

Key Exclusion Criteria:

• Received chronic opioid therapy within 4 weeks
• Received a sympathetic nerve block within 3 weeks
• Active litigation or a pending workers' compensation decision
• Any other clinically significant medical or pain condition (eg, Parkinson's disease, cognitive impairment, or fibromyalgia) or clinical laboratory abnormality that would in the investigator's judgment interfere with the subject's ability to participate in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, United Kingdom, United States

Administrative Information

• NCT Number: NCT02504008
• Other Study ID Numbers: AXS02-301
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Axsome Therapeutics, Inc.
• Study Sponsor: Axsome Therapeutics, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Axsome Therapeutics, Inc.
• Verification Date: March 2018