A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson's Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT01176240
First received: July 30, 2010
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

This is a study to evaluate the effects of an investigational drug, Droxidopa, in participants with neurogenic orthostatic hypotension (NOH), associated with Parkinson's disease. Droxidopa is being studied to determine the effects on blood pressure changes upon standing up (orthostatic challenge). Symptoms and activity measurements, including patient reported falls, will be evaluated to determine the effectiveness of the study drug.

Symptoms of NOH may include any of the following:

  • Dizziness, light-headedness, feeling faint or feeling like you may blackout
  • Problems with vision (blurring, seeing spots, tunnel vision, etc.)
  • Weakness
  • Fatigue
  • Trouble concentrating
  • Head & neck discomfort (the coat hanger syndrome)
  • Difficulty standing for a short time or a long time
  • Trouble walking for a short time or a long time

The study duration is a maximum of approximately 14 weeks including up to 2 weeks for screening, up to 2 weeks for proper dose finding, followed by an 8 week treatment period and a follow-up visit after 2 weeks. A sufficient number of patients will be screened to allow approximately 211 randomized patients. An extension study is also available to continue treatment if determined appropriate by the study doctor. This Study is NCT01132326 sponsored by Chelsea Therapeutics and is enrolling by invitation only.


Condition Intervention Phase
Orthostatic Hypotension
Parkinson's Disease
Drug: Droxidopa
Other: 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, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Double-blind, Randomized, Parallel-Group, Placebo-Controlled Study to Assess the Clinical Effect of Droxidopa in the Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Patients With Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • 306A Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]

    The primary efficacy endpoint for 306A is the relative mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to end of study. The OHQ is the average of two sub-scales, the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). Each asks the patient to rate their symptoms or disease impact over the past week. The OHSA sub-scale is the average of six items: 1) Dizziness, lightheadedness, feeling faint or feeling like you might black out; 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. The OHDAS sub-scale is the average of four items: 1) Standing for a short time; 2) Standing for a long time; 3) Walking for a short time; and 4) Walking for a long time. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe.

    For the change from baseline, negative numbers represent improvement from baseline in OHQ score.


  • 306B Efficacy: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1) [ Time Frame: Baseline, Week1 ] [ Designated as safety issue: No ]
    OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 1 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.


Secondary Outcome Measures:
  • 306B Efficacy: Change in OHSA Item 1 From Baseline to Week 2 (Visit 5) [ Time Frame: Baseline, Week2 ] [ Designated as safety issue: No ]
    OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 2 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

  • 306B Efficacy: Change in OHSA Item 1 From Baseline to Week 4 (Visit 6) [ Time Frame: Baseline, Week4 ] [ Designated as safety issue: No ]
    OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 4 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

  • 306B Efficacy: Change in Systolic Blood Pressure (SBP) Measurements Post Standing From Baseline to Week 1 [ Time Frame: Baseline, Week 1 ] [ Designated as safety issue: No ]
    Measure: Lowest standing systolic blood pressure reading of immediately post standing and 3 minutes post standing. Change: standing systolic blood pressure at Week 1 (Visit 4) minus standing systolic blood pressure at baseline. A positive score indicates an improvement in standing systolic blood pressure during the double-blind randomized phase relative to value at baseline.

  • 306B Efficacy: Change in OHSA Item 1 From Baseline to Week 8 (Visit 7) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    OHSA item 1 scale range: 0 (none) -10 (worst), likert scale. Change: score at Week 8 minus score at baseline. A negative score indicates an improvement in symptoms during the double-blind randomized phase relative to value at baseline.

  • 306B Efficacy: Rate of Patient Reported Falls [ Time Frame: up to 10 weeks ] [ Designated as safety issue: Yes ]
    The average number of patient reported falls per week.

  • 306B Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]

    The relative mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from baseline to end of study. The OHQ is the average of two sub-scales, the Orthostatic Hypotension Symptom Assessment Scale (OHSA) and the Orthostatic Hypotension Daily Activities Scale (OHDAS). Each asks the patient to rate their symptoms or disease impact over the past week. The OHSA sub-scale is the average of six items: 1) Dizziness, lightheadedness, feeling faint or feeling like you might black out; 2) Problems with vision; 3) Weakness; 4) Fatigue; 5) Trouble concentrating; and 6) Head/neck discomfort. The OHDAS sub-scale is the average of four items: 1) Standing for a short time; 2) Standing for a long time; 3) Walking for a short time; and 4) Walking for a long time. Each item is scored on a Likert scale from 0 to 10, with 10 being the most severe.

    For the change from baseline, negative numbers represent improvement from baseline in OHQ score.



Enrollment: 225
Study Start Date: June 2010
Study Completion Date: November 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Droxidopa
droxidopa active drug
Drug: Droxidopa
100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment
Other Names:
  • Northera
  • Droxidopa
  • L-DOPS
  • L-threo-dihydroxyphenylserine
  • SM-5688
Placebo Comparator: Placebo
Placebo matched control
Other: Placebo
Placebo
Other Name: Mannitol, Sugar Pill

  Show Detailed Description

  Eligibility

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

Inclusion criteria:

  1. 18 years or over
  2. Clinical diagnosis of Parkinson's disease
  3. Clinical diagnosis of symptomatic neurogenic orthostatic hypotension

At their baseline visit (Visit 2), patients must demonstrate:

  • a score of at least 3 or greater on the OHQ composite
  • a score of at least 3 or greater on the clinician CGI-S
  • a fall of at least 20 mmHg in their systolic blood pressure, or 10 mmHg in their diastolic 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;

    - 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. Concomitant use of anti-hypertensive medication for the treatment of essential hypertension
  4. Have changed dose, frequency or type of prescribed medication, within two weeks of baseline visit (Visit 2) with the following exceptions:

    • Vasoconstricting agents such a ephedrine, dihydroergotamine, or midodrine
    • Short courses (less than 2 weeks) of medications or treatments that do not interfere with, or exacerbate the patient's condition under study (e.g. antibiotics)
  5. Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV definition of alcohol or substance abuse)
  6. Women who are pregnant or breastfeeding
  7. Women of child bearing potential (WOCP) who are not using at least one method of contraception with their partner
  8. Male patients who are sexually active with a woman of child bearing potential (WOCP) and not using at least one method of contraception
  9. Untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the patient
  10. Sustained severe hypertension (BP ≥ 180 mmHg systolic or ≥ 110 mmHg diastolic in the seated or supine position which is observed in 3 consecutive measurements over an hour)
  11. Any significant uncontrolled cardiac arrhythmia
  12. History of myocardial infarction, within the past 2 years
  13. Current unstable angina
  14. Congestive heart failure (NYHA Class 3 or 4)
  15. Diabetic autonomic neuropathy
  16. 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
  17. Gastrointestinal condition, which in the Investigator's judgment, may affect the absorption of study drug (e.g. ulcerative colitis, gastric bypass)
  18. Any major surgical procedure within 30 days of the baseline visit (Visit 2)
  19. Previously treated with droxidopa
  20. Currently receiving any investigational drug or have received an investigational drug within 30 days of the baseline visit (Visit 2)
  21. 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. Additionally 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: NCT01176240

  Show 60 Study Locations
Sponsors and Collaborators
Chelsea Therapeutics
Investigators
Principal Investigator: Robert Hauser, M.D. University of South Florida
Study Chair: Lawrence A. Hewitt, Ph.D. Chelsea Therapeutics, Inc.
Study Director: William Schwieterman, M.D. Chelsea Therapeutics, Inc.
  More Information

Additional Information:
Publications:
Malamut, R., Freeman, R., Gilden, J., Tulloch, J., Kaufmann, H., 2005. A multi-center, double-blind, randomized, placebo controlled, cross-over study to assess the clinical benefit of midodrine in patients with neurogenic orthostatic hypotension. Clin. Auto. Res. 15 (5) 337[abstract].
Narabayashi, H., Nakanishi, T., Kanazawa, I., Yoshida, M., Mizuno, Y., Yanagisawa, N., Kondo, T. 1987. Clinical effects of L-threo-3,4-dihydroxyphenylserine in Parkinson's disease and Parkinson syndrome: Results of multi-center open study at 45 institutions. Yakuri To Chiryo (Jpn. Pharmacol. Ther.) 15(Suppl. 2):411 to 443.
Sobue, I., Senda, Y., Suzuki, T., Narabayashi, I., Hirayama, K. 1987. Clinical effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in Shy-Drager Syndrome and its related diseases. Shinkei Naika Chiryo [Neurol. Ther.] 4(2):199-208.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT01176240     History of Changes
Other Study ID Numbers: Droxidopa NOH306 (306A / 306B)
Study First Received: July 30, 2010
Results First Received: March 18, 2014
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Chelsea Therapeutics:
lightheadedness
unsteadiness
dizziness
weak
fatigue
concentration
head & neck pain
standing/walking for a short time
standing/walking for a long time
Neurogenic Orthostatic Hypotension
falls
NOH
Parkinson's disease
weakness

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

ClinicalTrials.gov processed this record on August 28, 2014