Fixed Versus Flexible Dosing of Pregabalin in Patients With Fibromyalgia (Flexdose)

A 9-week randomized double-blind, multi-center study of 172 patients, who after 1 week baseline evaluation are randomized to either fixed dose pregabalin starting at 75 mg BID for one week and increased to 150 mg BID for 7 weeks or flexibly dosed pregabalin given BID (75-300 mg/d) increased gradually over 4 weeks then maintained at that same dosing for 4 weeks.It is proposed that use of flexible dosing combined with nightly dosing would have similar pain relief to fixed dosing, would improve adherence, would have less side effects and would be more likely to improve sleep.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Pregabalin

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • David Silver MD Inc
    • Beverly Hills, California, United States, 90211
      • Stuart L Silverman MD Inc.
    • Huntington Beach, California, United States, 92646
      • Talbert Medical Group
    • Tucson, California, United States, 85704
      • Catalina Pointe Clinial Research
    • West Hills, California, United States, 91307
      • Affilaites in Medical Specialty

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• diagnosis of fibromyalgia by ACR criteria
• ambulatory patients
• complete of 5 pain diaries during 1 week evaluation
• other inclusion criteria may apply

Exclusion Criteria:

• pregnant or of childbearing potential not using contraceptives
• use of pregabalin in the past
• concomitant use of opioids or gabapentin
• estimated creatinine clearance less than 60
• other criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Flexible Dose; flexibly dosed pregabalin given BID (75-300 mg/d) increased gradually over 4 weeks then maintained at that same dosing for 4 weeks	Drug: Pregabalin; Fixed dosing of pregabalin: Week 1: 75 mg bid. Weeks 2 - 8: 150 mg bid. Week 9 (Days 57-60 and Days 61-63): 75 mg bid. Flexible dosing of pregabalin: Week 1: placebo in the AM and 75 mg nightly; Week 2: placebo in the AM and 150 mg nightly.; Week 3 placebo in the a.m., 225 mg nightly; Weeks 4 - 8 placebo in the a.m., 300 mg nightly. Week 9 (Days 57-60) placebo in the a.m,, 150 mg bid nightly and Days 61-63: placebo in the a.m., and 75 mg bid nightly.
Active Comparator: Fixed Dosing; 75 mg BID for one week and increased to 150 mg BID for 7 weeks	Drug: Pregabalin; Fixed dosing of pregabalin: Week 1: 75 mg bid. Weeks 2 - 8: 150 mg bid. Week 9 (Days 57-60 and Days 61-63): 75 mg bid. Flexible dosing of pregabalin: Week 1: placebo in the AM and 75 mg nightly; Week 2: placebo in the AM and 150 mg nightly.; Week 3 placebo in the a.m., 225 mg nightly; Weeks 4 - 8 placebo in the a.m., 300 mg nightly. Week 9 (Days 57-60) placebo in the a.m,, 150 mg bid nightly and Days 61-63: placebo in the a.m., and 75 mg bid nightly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score evaluation by NRS	Least square mean change in Fibromyalgia pain at 8weeks compared to baseline utilizing an 11 point numerical rating scale daily pain diary (0 = no pain to 10 =worst possible pain) performed at daily awakening.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change		At weeks 4 and 8
Discontinuation rate	Discontinuation rates due to lack of efficacy and discontinuation rates due to adverse event.	9 weeks
Improvements in Wolfe Symptom Severity Score	Wolfe Symptom Severity scales for pain, fatigue, trouble sleeping, trouble with anxiety or depression, trouble thinking or remembering, overall FM severity, problems awaking feeling unrefreshed	9 weeks

Collaborators and Investigators

• Sponsor: Osteoporosis Medical Center, Beverly Hills, CA
• Collaborators: Pfizer
• Investigators: Study Director: Keaton Nasser, Osteoporosis Medical Center; Principal Investigator: Stuart L Silverman, M.D., Osteoporosis Medical Center

Publications and helpful links

General Publications

• Nasser K, Kivitz AJ, Maricic MJ, Silver DS, Silverman SL. Twice daily versus once nightly dosing of pregabalin for fibromyalgia: a double-blind randomized clinical trial of efficacy and safety. Arthritis Care Res (Hoboken). 2014 Feb;66(2):293-300. doi: 10.1002/acr.22111.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 20, 2010
• First Posted (Estimate): October 22, 2010

Study Record Updates

• Last Update Posted (Estimate): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 30, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: fibromyalgia; pregabalin; lyrica
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: SLS2009001