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
Results First Received: March 18, 2014  
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
Conditions: Orthostatic Hypotension
Parkinson's Disease
Interventions: Drug: Droxidopa
Other: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Post-randomization, up to 2 weeks dose titration followed by 8 wks at optimal dose.

The first 51 patients enrolled in the study were analyzed as a separate group in an interim analysis (Study 306A).

The final 171 patients remained blinded until the end of the study and analyzed as a separate study (Study 306B).


Reporting Groups
  Description
Droxidopa

droxidopa active drug

Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment

Placebo

Placebo matched control

Placebo: Placebo


Participant Flow for 2 periods

Period 1:   Study 306A
    Droxidopa     Placebo  
STARTED     24     27  
COMPLETED     21     24  
NOT COMPLETED     3     3  
Lack of Efficacy                 2                 1  
Protocol Violation                 0                 1  
Withdrawal by Subject                 0                 1  
Stop due to diverse problems                 1                 0  

Period 2:   Study 306B
    Droxidopa     Placebo  
STARTED     89     85  
Took at Least 1 Dose of Study Drug     87 [1]   84 [2]
1 wk of Stable Dosing and Visit 4     69     78  
2 wk of Stable Dosing and Visit 5     68     75  
4 wk of Stable Dosing and Visit 6     67     73  
COMPLETED     63     68  
NOT COMPLETED     26     17  
Lack of Efficacy                 5                 3  
Adverse Event                 10                 5  
Protocol Violation                 2                 3  
Withdrawal by Subject                 4                 1  
Physician Decision                 2                 1  
Supine Hypertension                 1                 2  
Lost to Follow-up                 0                 1  
withdrew prior to dosing                 2                 1  
[1] Two randomized patients discontinued before receiving study drug.
[2] One randomized patient discontinued before receiving study drug.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

The population only includes those patients who were randomized and took at least one dose of study drug (n=222).

The first 51 patients enrolled in the study were analyzed as a separate group in an interim analysis (Study 306A).

The final 171 patients remained blinded until the end of the study and analyzed as a separate study (Study 306B).


Reporting Groups
  Description
Study 306A: Droxidopa

droxidopa active drug

Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment

Study 306A: Placebo

Placebo matched control

Placebo: Placebo

Study 306B: Droxidopa

droxidopa active drug

Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment

Study 306B: Placebo

Placebo matched control

Placebo: Placebo

Total Total of all reporting groups

Baseline Measures
    Study 306A: Droxidopa     Study 306A: Placebo     Study 306B: Droxidopa     Study 306B: Placebo     Total  
Number of Participants  
[units: participants]
  24     27     87     84     222  
Age  
[units: years]
Mean ± Standard Deviation
  72.2  ± 7.30     72.9  ± 7.76     72.5  ± 7.64     72.2  ± 7.97     72.4  ± 7.78  
Gender  
[units: participants]
         
Female     10     10     27     30     77  
Male     14     17     60     54     145  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     0     0     0     0     0  
Asian     0     0     1     0     1  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0  
Black or African American     0     2     2     1     5  
White     24     25     84     83     216  
More than one race     0     0     0     0     0  
Unknown or Not Reported     0     0     0     0     0  
Region of Enrollment  
[units: participants]
         
United States     24     27     87     84     222  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   306A Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ)   [ Time Frame: Baseline, Week 8 ]

2.  Primary:   306B Efficacy: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1)   [ Time Frame: Baseline, Week1 ]
  Hide Outcome Measure 2

Measure Type Primary
Measure Title 306B Efficacy: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1)
Measure Description 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.
Time Frame Baseline, Week1  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The primary analysis was defined as those patients who completed 1 week of dosing at the identified optimal dose of study medication and completed the visit 4 (1 week) efficacy evaluation. Patients who did not have week 1 efficacy data were excluded from the analysis.

Reporting Groups
  Description
Droxidopa

droxidopa active drug

Droxidopa: 100 mg and 200 mg capsules 100, 200, 300, 400, 500, 600mg TID dosing for up to 8 weeks of treatment

Placebo

Placebo matched control

Placebo: Placebo


Measured Values
    Droxidopa     Placebo  
Number of Participants Analyzed  
[units: participants]
  69     78  
306B Efficacy: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1)  
[units: units on a scale]
Mean ± Standard Deviation
  -2.3  ± 2.95     -1.3  ± 3.16  


Statistical Analysis 1 for 306B Efficacy: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1)
Groups [1] All groups
Method [2] Mantel Haenszel
P Value [3] 0.018
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Mantel-Haenszel statistic comparing treatment groups based on rank statistics adjusted for the covariate OHSA Item 1 value at baseline.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical analysis plan involved a hierarchical assessment of secondary endpoints to prevent inflation of type I errors.



3.  Secondary:   306B Efficacy: Change in OHSA Item 1 From Baseline to Week 2 (Visit 5)   [ Time Frame: Baseline, Week2 ]

4.  Secondary:   306B Efficacy: Change in OHSA Item 1 From Baseline to Week 4 (Visit 6)   [ Time Frame: Baseline, Week4 ]

5.  Secondary:   306B Efficacy: Change in Systolic Blood Pressure (SBP) Measurements Post Standing From Baseline to Week 1   [ Time Frame: Baseline, Week 1 ]

6.  Secondary:   306B Efficacy: Change in OHSA Item 1 From Baseline to Week 8 (Visit 7)   [ Time Frame: Baseline, Week 8 ]

7.  Secondary:   306B Efficacy: Rate of Patient Reported Falls   [ Time Frame: up to 10 weeks ]

8.  Secondary:   306B Efficacy: Change in Orthostatic Hypotension Questionnaire Score (OHQ)   [ Time Frame: Baseline, Week 8 ]

9.  Post-Hoc:   306A Efficacy: Patient Reported Falls   [ Time Frame: Baseline, Week 8 ]

10.  Post-Hoc:   Study 306A: Change in Dizziness/Lightheadedness/Feeling Faint/Feeling Like You Might Black Out (OHSA Item 1) From Baseline to Week 1   [ Time Frame: Baseline, Week 1 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Scientific Officer
Organization: Chelsea Therapeutics Inc.
phone: 704-973-4202
e-mail: hewitt@chelsearx.com


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.

Publications automatically indexed to this study:

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