Study To Assess The Clinical Benefit Of Droxidopa And Droxidopa/Carbidopa In Subjects With Fibromyalgia (FMS201)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT01323374
First received: March 24, 2011
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

A correlation between increased norepinephrine concentration in the central nervous system (CNS) and a decrease in fibromyalgia pain has been suggested in clinical studies. Therefore, as a pro-drug of norepinephrine, droxidopa could potentially benefit fibromyalgia patients by reducing pain as a result of increasing CNS levels of norepinephrine.

As this benefit is presumed to be a central effect, the addition of carbidopa, a peripheral DOPA decarboxylase (DDC) inhibitor, may favorably impact the drug's treatment profile. Carbidopa is utilized as a blocker of peripheral DDC, an enzyme required for the conversion of droxidopa into norepinephrine. Therefore, inhibition of peripheral DDC should result in a reduction of any side effects resulting from the peripheral production of norepinephrine, whilst allowing for increased central levels, and hence, increased centrally mediated benefits.

The purpose of the study is the obtain information regarding the proper dosing, effectiveness and safety of droxidopa and combination droxidopa/carbidopa treatments in patients with fibromyalgia.


Condition Intervention Phase
Fibromyalgia
Drug: Droxidopa
Drug: Carbidopa
Drug: Droxidopa/carbidopa
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Response, Study To Assess The Clinical Benefit Of Droxidopa and Droxidopa/Carbidopa In Subjects With Fibromyalgia

Resource links provided by NLM:


Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • Determine the efficacy of droxidopa and droxidopa/carbidopa in the treatment of pain associated with fibromyalgia [ Time Frame: Baseline to end of 8 week treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the effect of droxidopa and combinations of droxidopa/carbidopa on signs and symptoms of fibromyalgia (including depression, fatigue, and sleep disorder) [ Time Frame: Baseline to end of 8 week treatment period ] [ Designated as safety issue: No ]
  • Evaluate the effect of droxidopa and combinations of droxidopa/carbidopa on the overall quality of life of fibromyalgia patients [ Time Frame: Baseline to end of 8 week treatment period ] [ Designated as safety issue: No ]
  • Evaluate the dose-response relationship for droxidopa (200, 400, and 600mg TID), carbidopa (25 and 50mg TID) and combinations of droxidopa/carbidopa (200/25, 200/50, 400/25, 400/50, 600/25 and 600/50mg TID) in the treatment of fibromyalgia patients [ Time Frame: Baseline to end of 8 week treatment period ] [ Designated as safety issue: No ]
  • Evaluate the clinical benefit of treatment with 200, 400, and 600mg droxidopa TID, or 25 and 50mg carbidopa TID and combinations of droxidopa/carbidopa 200/25, 200/50, 400/25, 400/50, 600/25 and 600/50mg TID in the treatment of fibromyalgia patients [ Time Frame: Baseline to end of 8 week treatment period ] [ Designated as safety issue: No ]
  • Estimate the optimal dose for relief of fibromyalgia pain using response surface methodology [ Time Frame: Baseline to end of 8 week treatment period ] [ Designated as safety issue: No ]
  • Evaluate the safety of droxidopa and droxidopa/carbidopa treatments based on the occurrence of treatment-emergent adverse events (AE) and specific evaluation of blood pressure, heart rate, ECG, and laboratory findings across the study. [ Time Frame: Baseline to end of 4 week follow-up period following 8 week treatment period ] [ Designated as safety issue: Yes ]

Enrollment: 120
Study Start Date: January 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Droxidopa 200mg TID Drug: Droxidopa
Oral, 200mg, 400mg or 600mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine
  • L-threo-DOPS
  • L-DOPS
Experimental: Droxidopa 400mg TID Drug: Droxidopa
Oral, 200mg, 400mg or 600mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine
  • L-threo-DOPS
  • L-DOPS
Experimental: Droxidopa 600mg TID Drug: Droxidopa
Oral, 200mg, 400mg or 600mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine
  • L-threo-DOPS
  • L-DOPS
Active Comparator: Carbidopa 25mg TID Drug: Carbidopa
Oral, 25mg, or 50mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.
Other Name: Lodosyn
Active Comparator: Carbidopa 50 mg TID Drug: Carbidopa
Oral, 25mg, or 50mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.
Other Name: Lodosyn
Experimental: Droxidopa/carbidopa 200mg/25mg TID Drug: Droxidopa/carbidopa
Oral, 200mg/25mg, 400mg/25mg, 600mg/25mg, 200mg/50mg, 400mg/50mg, or 600mg/50mg TID. Duration includes up to a 1 week titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine / Lodosyn
  • L-threo-DOPS / Lodosyn
  • L-DOPS / Lodosyn
Experimental: Droxidopa/carbidopa 400mg/25mg TID Drug: Droxidopa/carbidopa
Oral, 200mg/25mg, 400mg/25mg, 600mg/25mg, 200mg/50mg, 400mg/50mg, or 600mg/50mg TID. Duration includes up to a 1 week titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine / Lodosyn
  • L-threo-DOPS / Lodosyn
  • L-DOPS / Lodosyn
Experimental: Droxidopa/carbidopa 600mg/25mg TID Drug: Droxidopa/carbidopa
Oral, 200mg/25mg, 400mg/25mg, 600mg/25mg, 200mg/50mg, 400mg/50mg, or 600mg/50mg TID. Duration includes up to a 1 week titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine / Lodosyn
  • L-threo-DOPS / Lodosyn
  • L-DOPS / Lodosyn
Experimental: Droxidopa/carbidopa 200mg/50mg TID Drug: Droxidopa/carbidopa
Oral, 200mg/25mg, 400mg/25mg, 600mg/25mg, 200mg/50mg, 400mg/50mg, or 600mg/50mg TID. Duration includes up to a 1 week titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine / Lodosyn
  • L-threo-DOPS / Lodosyn
  • L-DOPS / Lodosyn
Experimental: Droxidopa/carbidopa 400mg/50mg TID Drug: Droxidopa/carbidopa
Oral, 200mg/25mg, 400mg/25mg, 600mg/25mg, 200mg/50mg, 400mg/50mg, or 600mg/50mg TID. Duration includes up to a 1 week titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine / Lodosyn
  • L-threo-DOPS / Lodosyn
  • L-DOPS / Lodosyn
Experimental: Droxidopa/carbidopa 600mg/50mg TID Drug: Droxidopa/carbidopa
Oral, 200mg/25mg, 400mg/25mg, 600mg/25mg, 200mg/50mg, 400mg/50mg, or 600mg/50mg TID. Duration includes up to a 1 week titration period followed by an 8 week treatment period.
Other Names:
  • L-threo-3,4-dihydroxyphenylserine / Lodosyn
  • L-threo-DOPS / Lodosyn
  • L-DOPS / Lodosyn
Placebo Comparator: Placebo TID Drug: Placebo
Oral, placebo TID
Other Name: Inactive ingrediant

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female and aged 18 years or over
  • Clinical diagnosis of fibromyalgia as defined by the 1990 American College of Rheumatology (ACR) criteria
  • Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care
  • Have a score of between 20mm and 90mm on the Visual Analog Scale for Pain (VAS-P) section of the SF-MPQ at screening and baseline visits

Exclusion Criteria:

  • Have uncontrolled hypertension (defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >110 mmHg) or use of ≥2 antihypertensive medications
  • Patients currently taking pregabalin; unless they provide written informed consent and agree to discontinue pregabalin use 3 weeks prior to other screening procedures and for the duration of the study
  • Currently taking tri-cyclic antidepressant medication
  • Currently taking any norepinephrine re-uptake inhibitors
  • Have clinically relevant depression noted as significant by a score greater than 17 on the Hamilton Depression Scale (HAM-D)
  • History of known or suspected drug or substance abuse
  • Women of childbearing potential who are not using a medically accepted contraception (Reproductive potential: Female subjects should be either post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception throughout the study period and for 4 weeks after the last dose of investigational product. Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If hormonal contraceptives are used they should be taken according to the package insert. WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 4 weeks after the last dose of investigational product. For WOCP a urine pregnancy test must be conducted at screening, baseline and study termination; the results must be negative at screening and at baseline. Any positive result will be confirmed by serum beta HCG pregnancy test).
  • Sexually active males whose partner is a WOCP must agree to use condoms for the duration of the study and for 4 weeks after the last dose
  • Women who are pregnant, breast feeding, or plan to become pregnant during the course of this study
  • Known or suspected hypersensitivity to the study medication or any of its ingredients
  • Have in the investigator's opinion any significant cardiac arrhythmia
  • Any significant systemic, hepatic, cardiac or renal illness
  • Diabetes mellitus or insipidus
  • Have a history of closed angle glaucoma
  • Have a known or suspected current malignancy. Patients with a history of cancer must be symptom- and treatment-free for at least 5 years prior to randomization, with the exception of patients with non-melanoma, non-invasive skin cancers (such as basal cell carcinoma), who should not have had an intervention or recurrence within one year of starting the study
  • Patients with known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug
  • In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing
  • In the investigator's opinion, are unable to adequately co-operate because of individual or family situation
  • In the investigator's opinion, are suffering from a mental disorder that interferes with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major depression, dementia
  • Are not able or willing to comply with the study requirements for the duration of the study
  • Have participated in another clinical trial with an investigational agent (including named patient or compassionate use protocol) within 1 month before the start of the study
  • Previous enrollment in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01323374

Locations
United Kingdom
Rheumatology Department; Barnsley Hospital NHS Foundation Trust
Barnsley, United Kingdom, S75 2EP
MAC UK Neuroscience
Liverpool, United Kingdom, L18 1HQ
Academic Dept of Rheumatology, Kings College London
London, United Kingdom, SE5 9RJ
MAC UK Neuroscience
Manchester, United Kingdom, M32 0UT
Musculoskeletal Department; Freeman Hospital
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Rheumatology Department, Poole Hospital NHS Trust
Poole, United Kingdom, BH15 2JB
Clinical Trials Unit; Main Hospital; Salford Rooyal NHS Foundation Trust
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Chelsea Therapeutics
Investigators
Principal Investigator: Ernest Choy, M.D. Academic Dept of Rheumatology Kings College London
  More Information

Additional Information:
No publications provided

Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT01323374     History of Changes
Other Study ID Numbers: Droxidopa FMS201
Study First Received: March 24, 2011
Last Updated: July 18, 2012
Health Authority: United Kingdom: Department of Health

Keywords provided by Chelsea Therapeutics:
Fibromyalgia
FMS
droxidopa
pain

Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Rheumatic Diseases
Carbidopa
Droxidopa
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014