E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of pain associated with fibromyalgia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048439 |
E.1.2 | Term | Fibromyalgia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the efficacy of droxidopa and droxidopa/carbidopa in the treatment of pain associated with fibromyalgia |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the effect of droxidopa and droxidopa/carbidopa on signs and symptoms of fibromyalgia (including depression, fatigue, sleep disorder) • Evaluate the effect of droxidopa and droxidopa/carbidopa on the overall quality of life of fibromyalgia patients • Evaluate the dose-response relationship for droxidopa between the doses of 200, 400, and 600mg TID or carbidopa 25 and 50mg TID and droxidopa/carbidopa TID in the treatment of fibromyalgia patients • Evaluate the clinical benefit of treatment with combination 200, 400, and 600mg droxidopa TID or 25 and 50mg carbidopa or droxidopa/carbidopa TID, in fibromyalgia patients • Estimate the optimal dose for relief of fibromyalgia pain using response surface methodology • 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patients; • Aged at least 18 years; • Diagnosed with fibromyalgia as defined by the 1990 American College of Rheumatology (ACR) criteria. • Have a score between 20mm and 90mm on the Visual Analog Scale for Pain (VAS-P) section of the SF-MPQ at screening and baseline visits |
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E.4 | Principal exclusion criteria |
• Currently taking any norepinephrine re-uptake inhibitors; • Currently taking tri-cyclic antidepressant medication; • 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 • Have clinically relevant depression noted as significant by 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; • Sexually active males whose partner is a WOCP who do not 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of efficacy will be the improvement of pain as demonstrated by:
• A decrease in the average pain score from baseline over 2 months of treatment according to Short-Form McGill Pain Questionnaire (SF-MPQ) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |