Study To Assess The Clinical Benefit Of Droxidopa And Droxidopa/Carbidopa In Subjects With Fibromyalgia (FMS201)
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| ClinicalTrials.gov Identifier: NCT01323374 |
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Recruitment Status
:
Completed
First Posted
: March 25, 2011
Last Update Posted
: July 19, 2012
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Sponsor:
Chelsea Therapeutics
Information provided by (Responsible Party):
Chelsea Therapeutics
- Study Details
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Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Fibromyalgia | Drug: Droxidopa Drug: Carbidopa Drug: Droxidopa/carbidopa Drug: Placebo | Phase 2 |
Show Detailed Description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 120 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, 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 |
| Study Start Date : | January 2009 |
| Actual Primary Completion Date : | October 2011 |
| Actual Study Completion Date : | October 2011 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Fibromyalgia
U.S. FDA Resources
| Arm | Intervention/treatment |
|---|---|
| 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:
|
| 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:
|
| 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:
|
| 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
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| 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
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| 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:
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| 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:
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| 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:
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| 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:
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| 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:
|
| 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:
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| Placebo Comparator: Placebo TID |
Drug: Placebo
Oral, placebo TID
Other Name: Inactive ingrediant
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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 ]
Secondary Outcome Measures
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- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Estimate the optimal dose for relief of fibromyalgia pain using response surface methodology [ Time Frame: Baseline to end of 8 week treatment period ]
- 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 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 |
| Responsible Party: | Chelsea Therapeutics |
| ClinicalTrials.gov Identifier: | NCT01323374 History of Changes |
| Other Study ID Numbers: |
Droxidopa FMS201 |
| First Posted: | March 25, 2011 Key Record Dates |
| Last Update Posted: | July 19, 2012 |
| Last Verified: | July 2012 |
Keywords provided by Chelsea Therapeutics:
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Fibromyalgia FMS droxidopa pain |
Additional relevant MeSH terms:
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Fibromyalgia Myofascial Pain Syndromes Muscular Diseases Musculoskeletal Diseases Rheumatic Diseases Neuromuscular Diseases Nervous System Diseases Carbidopa Droxidopa |
Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Aromatic Amino Acid Decarboxylase Inhibitors Enzyme Inhibitors |