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

NCT01323374 | Completed Phase 2 DMC

• 1 other identifier: Droxidopa FMS201
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 7

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.

Conditions

Fibromyalgia

Keywords

Fibromyalgia; FMS; droxidopa; pain

Outcome Measures

Primary Outcomes (1)

• Determine the efficacy of droxidopa and droxidopa/carbidopa in the treatment of pain associated with fibromyalgia

  Baseline to end of 8 week treatment period

Secondary Outcomes (6)

• Evaluate the effect of droxidopa and combinations of droxidopa/carbidopa on signs and symptoms of fibromyalgia (including depression, fatigue, and sleep disorder)

  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

  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

  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

  Baseline to end of 8 week treatment period

• Estimate the optimal dose for relief of fibromyalgia pain using response surface methodology

  Baseline to end of 8 week treatment period

Study Arms (12)

Droxidopa 200mg TID

EXPERIMENTAL

Drug: Droxidopa

Droxidopa 400mg TID

EXPERIMENTAL

Drug: Droxidopa

Droxidopa 600mg TID

EXPERIMENTAL

Drug: Droxidopa

Carbidopa 25mg TID

ACTIVE COMPARATOR

Drug: Carbidopa

Carbidopa 50 mg TID

ACTIVE COMPARATOR

Drug: Carbidopa

Droxidopa/carbidopa 200mg/25mg TID

EXPERIMENTAL

Drug: Droxidopa/carbidopa

Droxidopa/carbidopa 400mg/25mg TID

EXPERIMENTAL

Drug: Droxidopa/carbidopa

Droxidopa/carbidopa 600mg/25mg TID

EXPERIMENTAL

Drug: Droxidopa/carbidopa

Droxidopa/carbidopa 200mg/50mg TID

EXPERIMENTAL

Drug: Droxidopa/carbidopa

Droxidopa/carbidopa 400mg/50mg TID

EXPERIMENTAL

Drug: Droxidopa/carbidopa

Droxidopa/carbidopa 600mg/50mg TID

EXPERIMENTAL

Drug: Droxidopa/carbidopa

Placebo TID

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Droxidopa DRUG

Oral, 200mg, 400mg or 600mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.

Also known as: L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, L-DOPS

Droxidopa 200mg TID; Droxidopa 400mg TID; Droxidopa 600mg TID

Carbidopa DRUG

Oral, 25mg, or 50mg TID, duration includes up to a 1 week blinded titration period followed by an 8 week treatment period.

Also known as: Lodosyn

Carbidopa 25mg TID; Carbidopa 50 mg TID

Droxidopa/carbidopa DRUG

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.

Also known as: L-threo-3,4-dihydroxyphenylserine / Lodosyn, L-threo-DOPS / Lodosyn, L-DOPS / Lodosyn

Droxidopa/carbidopa 200mg/25mg TID; Droxidopa/carbidopa 200mg/50mg TID; Droxidopa/carbidopa 400mg/25mg TID; Droxidopa/carbidopa 400mg/50mg TID; Droxidopa/carbidopa 600mg/25mg TID; Droxidopa/carbidopa 600mg/50mg TID

Placebo DRUG

Oral, placebo TID

Also known as: Inactive ingrediant

Placebo TID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (7)

Rheumatology Department; Barnsley Hospital NHS Foundation Trust

Barnsley, S75 2EP, United Kingdom

Location

MAC UK Neuroscience

Liverpool, L18 1HQ, United Kingdom

Location

Academic Dept of Rheumatology, Kings College London

London, SE5 9RJ, United Kingdom

Location

MAC UK Neuroscience

Manchester, M32 0UT, United Kingdom

Location

Musculoskeletal Department; Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Rheumatology Department, Poole Hospital NHS Trust

Poole, BH15 2JB, United Kingdom

Location

Clinical Trials Unit; Main Hospital; Salford Rooyal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

Related Links

• EudraCT summary results

MeSH Terms

Conditions

Fibromyalgia; Pain

Interventions

Droxidopa; 3,4-dihydroxyphenylserine aldolase; Carbidopa

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Methyldopa; Dihydroxyphenylalanine; Hydrazines

Study Officials

• Ernest Choy, M.D.

  Academic Dept of Rheumatology Kings College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2011
• First Posted: March 25, 2011
• Study Start: January 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: February 14, 2024

Record last verified: 2024-02

Locations

GB (7)