Symptomatic neurogenic orthostatic hypotension (NOH) in patients with Primary Autonomic Failure (PD, MSA and PAF), DBH deficiency and Non-Diabetic Neuropathy.
Conditions
Interventions
Trade Name: DOPS
Product Name: Droxidopa
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DROXIDOPA
CAS Number: 23651958
Sponsors
Chelsea Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Male or female and aged 18 years or over; b) Clinical diagnosis of orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency or Non-Diabetic Autonomic Neuropathies; c) A documented fall in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at least 10 mmHg, within 3 minutes after standing; d) 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a) Taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine; - Patients taking vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit (Visit 2); b) Currently taking anti-hypertensive medication -The use of short-acting anti-hypertensive medications at bedtime is permitted; c) Currently taking tri-cyclic antidepressant medication or other norepinephrine re-uptake inhibitors; d) Have changed dose, frequency and or type of prescribed medication, within two weeks of Baseline Visit (Visit 2), with the following exceptions: - vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine (see exclusion a), -s hort courses of antibiotics or other medications/treatments that do not interfere with, or exacerbate the patient’s condition under study. e) History of more than moderate alcohol consumption; f) History of known or suspected drug or substance abuse; g) Women of childbearing potential who are not using a medically accepted contraception; • Reproductive potential: Female subjects should be either post-menopausal (amenorrhoea 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. 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. • For WOCP a serum beta HCG pregnancy test must be conducted at screening and a urine pregnancy test must be conducted at baseline and study termination; the results must be negative at screening and at baseline for the patient to receive study medication. WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product. 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 30 days after the last dose of investigational product. h) Sexually active males whose partner is a WOCP and who do not agree to use condoms for the duration of the study and for 30 days after the last dose; i) Women who are pregnant or breast feeding; j) Known or suspected hypersensitivity to the study medication or any of its ingredients; k) Pre-existing sustained severe hypertension (BP greater than or equal to 180/110 mmHg in the sitting position); l) Have atrial fibrillation or, in the investigator’s opinion, have any other significant cardiac arrhythmia; m) Any other significant systemic, hepatic, cardiac or renal illness; n) Diabetes mellitus or insipidus; o) Have a history of closed angle glaucoma; p) Have a known or suspected malignancy; q) Patients with known gastrointestinal illness or other gastrointestinal disorder th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of droxidopa in patients with symptomatic neurogenic orthostatic hypotension as measured by the relative change in mean score of Item 1 of the Orthostatic Hypotension Symptom Assessment (OHSA) 14 days following randomization to continued therapy with droxidopa or placebo.; Secondary Objective: - To evaluate efficacy of droxidopa as measured by changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements 3 minutes post standing; - To evaluate the efficacy of droxidopa by global assessment evaluations using the clinician-recorded and patient-recorded Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales; - To evaluate efficacy of droxidopa by symptom and activity measurements using the composite scores of OHSA and OHDAS (the two subcomponents of the OHQ); - To evaluate the safety of droxidopa based on the occurrence of treatment-emergent adverse events and specific evaluation of blood pressure, heart rate, ECG, and laboratory findings across the study. - To develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for droxidopa within the target population. ; Primary end point(s): The primary efficacy variable is the relative mean change from randomization to 14 days post-randomization in the score of Item 1 of the OHSA. The OHSA is a 6 item questionnaire used to measure symptoms associated with orthostatic hypotension (see section 13.1.2). Item 1 of the OHSA asks the patient to rate using a 0 to 10 scale (0 meaning not bothered and 10 meaning the worst) his or her impression of the severity of “dizziness, lightheadedness, feeling faint, or “feeling like you might black out.” | — |
Countries
United Kingdom
Outcome results
None listed