Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT00102596
First received: January 30, 2005
Last updated: January 31, 2012
Last verified: January 2012
Results First Received: November 10, 2010  
Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Essential Tremor
Intervention: Drug: 1-Octanol

  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
No text entered.

Reporting Groups
  Description
Part A: Dose Escalation

Subjects fasted overnight for 6 hours and received 1, 4, 8, 16, 32 and 64 mg/kg 1-octanol at 6AM on different days. There were 2 formulations:

1) 2 participants received 1-octanol adsorbed to microcrystalline cellulose, NF (Avicel PH 102, FMC Corp., Philadelphia, PA), and fine particle silica (Sipernat 50S, Evonik Degussa Corp., Parsippany, NJ) and encapsulated in 50 mg and 250 mg dosages; and 2) two participants received a soft-gel capsule containing 1-octanol embedded in soybean oil at 50 mg and 800 mg dosages (Best Formulations Inc, City of Industry, CA).

Part B Then C: Fixed Dose

In Part B, subjects fasted overnight for 6 hours and received 64 mg/kg 1-octanol at 6AM of both formulations:

1) 1-octanol adsorbed to microcrystalline cellulose, NF (Avicel PH 102, FMC Corp., Philadelphia, PA), and fine particle silica (Sipernat 50S, Evonik Degussa Corp., Parsippany, NJ) and encapsulated in 50 mg and 250 mg dosages; or 2) a soft-gel capsule containing 1-octanol embedded in soybean oil at 50 mg and 800 mg dosages (Best Formulations Inc, City of Industry, CA).

At the completion of Parts A and B, an exploratory Part C was added in which subjects fasted overnight for 6 hours and received 128 mg/kg 1-octanol at 6AM of both formulations.


Participant Flow for 3 periods

Period 1:   Part A
    Part A: Dose Escalation     Part B Then C: Fixed Dose  
STARTED     11     0  
Participants Assigned Treatment     5     0  
COMPLETED     4     0  
NOT COMPLETED     7     0  
Screen failures                 6                 0  
Adverse Event                 1                 0  

Period 2:   Part B
    Part A: Dose Escalation     Part B Then C: Fixed Dose  
STARTED     0 [1]   10  
COMPLETED     0     10  
NOT COMPLETED     0     0  
[1] Participants from Part A did not continue to Part B

Period 3:   Part C
    Part A: Dose Escalation     Part B Then C: Fixed Dose  
STARTED     0     2 [1]
COMPLETED     0     2  
NOT COMPLETED     0     0  
[1] Only 2 patients participated in Part C



  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.
No text entered.

Reporting Groups
  Description
All Participants Baseline is included for all participants who passed screening and received at least 1 dose of 1-octanol, whether in Part A, B or C

Baseline Measures
    All Participants  
Number of Participants  
[units: participants]
  15  
Age  
[units: years]
Mean ± Standard Deviation
  68.1  ± 8.1  
Gender  
[units: participants]
 
Female     6  
Male     9  
Region of Enrollment  
[units: participants]
 
United States     15  
Height  
[units: centimeters]
Mean ± Standard Deviation
  169.6  ± 12.0  
Weight  
[units: kg]
Mean ± Standard Deviation
  82.9  ± 20.1  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  28.6  ± 4.7  
Age of onset  
[units: years]
Mean ± Standard Deviation
  39.5  ± 18.6  
Disease Duration  
[units: years]
Mean ± Standard Deviation
  28.7  ± 17.2  
History of alcohol-responsive tremors  
[units: participants]
  15  
Number of alcohol servings required for tremor response [1]
[units: servings]
Mean ± Standard Deviation
  2.1  ± 0.3  
Family history of essential tremor  
[units: participants]
  13  
Fahn Tolosa Marin Tremor Rating Scale [2]
[units: scores on a scale]
Mean ± Standard Deviation
  41.6  ± 17.6  
[1] One serving of alcohol is 50 ml of 40% ethanol
[2] Only available for the 10 participants who entered Part B. The Fahn Tolosa Marin Tremor Rating Scale was used. Minimum of this scale is 0, maximum is 164 points. Higher scores indicate more tremor. See Fahn S, Tolosa E, and Marin C (1993) "Clinical rating scale for tremor" reference provided in Protocol for full information.



  Outcome Measures
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1.  Primary:   Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B   [ Time Frame: 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose ]

2.  Secondary:   Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose   [ Time Frame: 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose ]

3.  Secondary:   Heart Rate Post 1-Octanol Dose   [ Time Frame: 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose ]

4.  Secondary:   PR and QTc Intervals Post 1-Octanol Dose   [ Time Frame: 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose ]


  Serious Adverse Events


  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
Enrollment to study was ended early, as evidence became available, that a metabolite of the study substance promised significantly higher feasibility for treatment in ET.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Mark Hallett, M.D.
Organization: NINDS/NIH
phone: 301-496-9526
e-mail: hallettm@ninds.nih.gov


Publications of Results:
Other Publications:

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT00102596     History of Changes
Obsolete Identifiers: NCT01195909
Other Study ID Numbers: 050092, 05-N-0092
Study First Received: January 30, 2005
Results First Received: November 10, 2010
Last Updated: January 31, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration