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

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
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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
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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 
Overall Participants Analyzed 
[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 ]

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
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Time Frame No text entered.
Additional Description

Subjects with more than 1 of a given AE, the subject is counted only once for that AE. Subject with more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.

Only dosed patients included in Safety Set.

Droxidopa Safety Set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa.


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

Droxidopa Safety set includes 3 patients randomized to placebo who were mistakenly dosed with droxidopa for short periods of time during the trial.

Placebo

Placebo matched control

Placebo: Placebo

Placebo Safety set excludes 3 patients randomized to placebo who were mistakenly dosed with droxidopa for short periods of time during the trial.


Serious Adverse Events
    Droxidopa   Placebo
Total, serious adverse events     
# participants affected / at risk   5/114 (4.39%)   4/108 (3.70%) 
Cardiac disorders     
Atrial fibrillation     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Gastrointestinal disorders     
Abdominal pain upper     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Faecaloma     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Inguinal hernia     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
General disorders     
Asthenia     
# participants affected / at risk   0/114 (0.00%)   1/108 (0.93%) 
# events   0   1 
Infections and infestations     
Bronchitis viral     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Upper respiratory tract infection bacterial     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Viral infection     
# participants affected / at risk   0/114 (0.00%)   1/108 (0.93%) 
# events   0   1 
Injury, poisoning and procedural complications     
Fibula fracture     
# participants affected / at risk   0/114 (0.00%)   1/108 (0.93%) 
# events   0   1 
Nervous system disorders     
Presyncope     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Syncope     
# participants affected / at risk   0/114 (0.00%)   2/108 (1.85%) 
# events   0   2 
Psychiatric disorders     
Mental status changes     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 
Vascular disorders     
Hypertension     
# participants affected / at risk   1/114 (0.88%)   0/108 (0.00%) 
# events   1   0 




  Other Adverse Events


  Limitations and Caveats
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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
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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 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