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

Tracking Information
First Submitted Date ICMJE	July 20, 2015
First Posted Date ICMJE	July 21, 2015
Last Update Posted Date	March 23, 2018
Actual Study Start Date ICMJE	July 2015
Estimated Primary Completion Date	January 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (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 ICMJE	Same as current
Change History	Complete list of historical versions of study NCT02504008 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (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 ICMJE; (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 Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	CREATE-1: A Study to Assess the Efficacy and Safety of AXS-02 in Patients With CRPS-1
Official Title ICMJE	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 ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Complex Regional Pain Syndrome; Reflex Sympathetic Dystrophy
Intervention ICMJE	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
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: July 20, 2015)	190
Original Estimated Enrollment ICMJE	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 ICMJE	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 ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Canada, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT02504008
Other Study ID Numbers ICMJE	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 ICMJE	Axsome Therapeutics, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Axsome Therapeutics, Inc.
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP