A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Chelsea Therapeutics
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT01927055
First received: August 16, 2013
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

Evaluate the clinical efficacy and safety of droxidopa versus placebo over a 17 week (maximum) treatment period in patients with symptomatic NOH.


Condition Intervention Phase
Symptomatic Neurogenic Orthostatic Hypotension
Parkinson's Disease
Multiple Systems Atrophy
Pure Autonomic Failure
Dopamine Beta Hydroxylase Deficiency
Drug: Droxidopa
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy

Resource links provided by NLM:


Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • OHSA Item 1 [ Time Frame: Change from Randomization to Week 1 ] [ Designated as safety issue: No ]
    Evaluate the duration of clinical benefits of droxidopa as demonstrated by the change in the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1


Secondary Outcome Measures:
  • Falls [ Time Frame: Change from Randomization to Week 12 ] [ Designated as safety issue: Yes ]
    Evaluate the clinical efficacy of droxidopa as demonstrated by a difference between placebo and droxidopa in patient reported falls from Randomization to the end of study visit at Week 12

  • Standing blood pressure [ Time Frame: Change from Randomization to Week 12 ] [ Designated as safety issue: No ]
    Evaluate the effect of droxidopa on standing blood pressure as demonstrated by a change from Randomization to the end of study visit at Week 12

  • Orthostatic Hypotension Questionnaire [ Time Frame: Change from Randomization to Week 12 ] [ Designated as safety issue: No ]
    Evaluate the clinical efficacy of droxidopa as demonstrated change in disease severity using the Orthostatic Hypotension Questionnaire (OHQ) composite score and individual item scores

  • Clinical Global Impression Scales [ Time Frame: Change from Randomization to Week 12 ] [ Designated as safety issue: No ]
    Evaluate the clinical efficacy of droxidopa as demonstrated by change in the clinician recorded and patient-recorded Clinical Global Impression-Severity (CGI-S) and the Clinical Global Impression-Improvement (CGI-I) scales from Randomization to the end of study visit at Week 12

  • Boston University Activity Measure for Post-Acute Care Basic Mobility [ Time Frame: Change from Randomization to Week 12 ] [ Designated as safety issue: No ]
    Evaluate the clinical efficacy of droxidopa as demonstrated by change in basic mobility using the Boston University Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Outpatient Short Form from Randomization to the end of study visit at Week 12


Estimated Enrollment: 450
Study Start Date: November 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Droxidopa
Droxidopa 100 mg, 200 mg, 300 mg
Drug: Droxidopa
Droxidopa at 100 mg, 200 mg, 300 mg
Other Name: L-threo-3,4-dihydroxyphenylserine, L-threo-DOPS, or L-DOPS
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo to match droxidopa capsules and strength designations
Other Name: Mannitol

Detailed Description:

This is a multi-center, multi-national, randomized, parallel-group, placebo-controlled, double-blind study with a 17 week (maximum) treatment period consisting of an initial, open-label dose titration (up to 2 weeks), followed by a washout period (up to 3 weeks), followed by a 12 week treatment period on a stable dose.

  Eligibility

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

Inclusion Criteria:

  • 1. 18 years and older and ambulatory (defined as able to walk at least 10 meters);

    2. Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA and PAF), Dopamine Beta Hydroxylase Deficiency;

    3. At the Baseline visit (Visit 2), patients must demonstrate:

    1. a score of at least 4 or greater on the Orthostatic Hypotension Symptom Assessment (OHSA) Item #1;
    2. a fall of at least 20 mmHg in their systolic blood pressure, within 3 minutes of standing;

      4. 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;

      Exclusion Criteria:

  • 1. Score of 23 or lower on the mini-mental state examination (MMSE);

    2. Concomitant use of vasoconstricting agents for the purpose of increasing blood pressure;

    1. 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) and throughout the duration of the study;

      3. Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV definition of alcohol or substance abuse);

      4. Women who are pregnant or breastfeeding;

      5. Women of child bearing potential (WOCP) who are not using at least one method of contraception with their partner;

      6. Male patients who are sexually active with a woman of child bearing potential (WOCP) and not using at least one method of contraception;

      7. Untreated closed angle glaucoma;

      8. Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine HTN are allowed in this study) Any significant uncontrolled cardiac arrhythmia;

      9. History of myocardial infarction, within the past 2 years;

      10. Current unstable angina;

      11. Congestive heart failure (NYHA Class 3 or 4);

      12. History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ;

      13. Gastrointestinal condition that may affect the absorption of study drug (e.g. ulcerative colitis, gastric bypass);

      14. Any major surgical procedure within 30 days prior to the Baseline visit (Visit 2);

      15. Previously treated with droxidopa within 30 days prior to the Baseline visit (Visit 2);

      16. Currently receiving any other investigational drug or have received an investigational drug within 30 days prior to the Baseline visit (Visit 2);

      17. Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study;

      18. The Investigator has the ability to exclude a patient if for any reason they feel the subject is not a good candidate for the study or will not be able to follow study procedures.

  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: NCT01927055

Contacts
Contact: Cameron Szakacs, Ph. D. 704-973-4203 szakacs@chelseaRx.com
Contact: Charles Cram, BS 7049734213 cram@chelseaRx.com

Locations
United States, New York
NYU Langone Medical Center Not yet recruiting
New York, New York, United States, 10016
Contact: Horacio Kaufmann, M.D.    212-263-7225    Horacio.Kaufmann@med.nyu.edu   
Principal Investigator: Horacio Kaufmann, M.D.         
United States, North Carolina
Information on additional locations involved in this clinical trial contact Chelsea Therapeutics Recruiting
Charlotte, North Carolina, United States, 28277
Contact: Cameron Szakacs, Ph. D.    704-973-4203    szakacs@chelseaRx.com   
United States, Wisconsin
Wisconsin Institute for Neurology and Sleep Disorders Recruiting
Milwaukee, Wisconsin, United States, 53233
Contact: Paul Nausieda, MD    414-219-7450    jklein@parkcent.com   
Sponsors and Collaborators
Chelsea Therapeutics
Investigators
Principal Investigator: Horacio Kaufmann, M.D. NYU Langone Medical Center
  More Information

No publications provided

Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT01927055     History of Changes
Other Study ID Numbers: NOH401
Study First Received: August 16, 2013
Last Updated: November 13, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Chelsea Therapeutics:
NOH
OH
PD
MSA
PAF
DBH

Additional relevant MeSH terms:
Autonomic Nervous System Diseases
Primary Dysautonomias
Hypotension
Hypotension, Orthostatic
Multiple System Atrophy
Parkinson Disease
Pure Autonomic Failure
Shy-Drager Syndrome
Basal Ganglia Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Orthostatic Intolerance
Parkinsonian Disorders
Vascular Diseases
Droxidopa
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014