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

Sponsor

Axsome Therapeutics, Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02504008

Collaborator

(none)

190

Enrollment

Locations

Arms

42.1

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Complex Regional Pain Syndrome Reflex Sympathetic Dystrophy	Drug: AXS-02 (oral zoledronate) Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

190 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 1, 2015

Anticipated Primary Completion Date :

Jan 1, 2019

Anticipated Study Completion Date :

Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AXS-02 (oral zoledronate) Administered orally in the morning on Days 1, 8, 15, 22, 29, and 36	Drug: AXS-02 (oral zoledronate) Once weekly for 6 weeks
Placebo Comparator: Placebo Administered orally in the morning on Day 1, 8, 15, 22, 29, and 36	Drug: Placebo Once weekly for 6 weeks

Arm

Intervention/Treatment

Experimental: AXS-02 (oral zoledronate)

Administered orally in the morning on Days 1, 8, 15, 22, 29, and 36

Drug: AXS-02 (oral zoledronate)

Once weekly for 6 weeks

Placebo Comparator: Placebo

Administered orally in the morning on Day 1, 8, 15, 22, 29, and 36

Drug: Placebo

Once weekly for 6 weeks

Outcome Measures

Primary Outcome Measures

Change in patient reported pain intensity [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).

Secondary Outcome Measures

Change in Brief Pain Inventory (BPI) Pain Score [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) [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) [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) [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) [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 [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Tucson	Arizona	United States
2	Hot Springs	Arkansas	United States
3	Encinitas	California	United States
4	La Jolla	California	United States
5	Los Angeles	California	United States
6	Napa	California	United States
7	Temecula	California	United States
8	Denver	Colorado	United States
9	Clermont	Florida	United States
10	Miami	Florida	United States
11	Orlando	Florida	United States	32827
12	Tampa	Florida	United States
13	West Palm Beach	Florida	United States
14	Canton	Georgia	United States
15	Marietta	Georgia	United States
16	Saint Marys	Georgia	United States	31558
17	Meridian	Idaho	United States
18	Chicago	Illinois	United States
19	Louisville	Kentucky	United States
20	Albuquerque	New Mexico	United States
21	New York	New York	United States
22	Winston-Salem	North Carolina	United States
23	Oklahoma City	Oklahoma	United States
24	Portland	Oregon	United States
25	Dallas	Texas	United States
26	San Antonio	Texas	United States
27	Bellevue	Washington	United States
28	Seattle	Washington	United States
29	Madison	Wisconsin	United States
30	Broadmeadow	New South Wales	Australia
31	Hurstville	New South Wales	Australia
32	Noosa Heads	Queensland	Australia
33	Welland	South Australia	Australia
34	Clayton	Victoria	Australia
35	Nedlands	Western Australia	Australia
36	Sherbrooke	Quebec	Canada
37	Warrington	Cheshire	United Kingdom
38	Darlington	County Durham	United Kingdom
39	Lambeth	London	United Kingdom
40	Liverpool	Merseyside	United Kingdom
41	Norwich	Norfolk	United Kingdom
42	Newcastle upon Tyne	Tyne And Wear	United Kingdom
43	Glasgow		United Kingdom
44	London		United Kingdom