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

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ClinicalTrials.gov Identifier: NCT00102596
Recruitment Status : Completed
First Posted : January 31, 2005
Results First Posted : February 1, 2012
Last Update Posted : February 1, 2012
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Essential Tremor
Intervention Drug: 1-Octanol
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part A: Dose Escalation Part B Then C: Fixed Dose
Hide Arm/Group Description

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).

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.

Period Title: Part A
Started 11 0
Participants Assigned Treatment 5 0
Completed 4 0
Not Completed 7 0
Reason Not Completed
Screen failures             6             0
Adverse Event             1             0
Period Title: Part B
Started 0 [1] 10
Completed 0 10
Not Completed 0 0
[1]
Participants from Part A did not continue to Part B
Period Title: Part C
Started 0 2 [1]
Completed 0 2
Not Completed 0 0
[1]
Only 2 patients participated in Part C
Arm/Group Title All Participants
Hide Arm/Group Description 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
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
68.1  (8.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
6
  40.0%
Male
9
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 15 participants
169.6  (12.0)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 15 participants
82.9  (20.1)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 15 participants
28.6  (4.7)
Age of onset  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
39.5  (18.6)
Disease Duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
28.7  (17.2)
History of alcohol-responsive tremors  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
15
Number of alcohol servings required for tremor response   [1] 
Mean (Standard Deviation)
Unit of measure:  Servings
Number Analyzed 15 participants
2.1  (0.3)
[1]
Measure Description: One serving of alcohol is 50 ml of 40% ethanol
Family history of essential tremor  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
13
Fahn Tolosa Marin Tremor Rating Scale   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 15 participants
41.6  (17.6)
[1]
Measure Description: 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.
1.Primary Outcome
Title Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Hide Description Spirography mean tremor amplitudes were measured in the right hand of each participant at 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose. Then, the scores of each participant were normalized (i.e., divided by) by their baseline tremor severity scores so that all scores are expressed as a proportion of the baseline score. Therefore, 1 is the baseline tremor severity, and lower scores indicate tremor reduction.
Time Frame 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received both formulations of 64 mg/kg 1-octanol in Part B
Arm/Group Title 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation
Hide Arm/Group Description:
Subjects fasted overnight for 6 hours. At 6AM subjects received 64 mg/kg of the 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.
Subjects fasted overnight for 6 hours. At 6AM subjects received 64 mg/kg of the 1-octanol in 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).
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: normalized score on a scale
Normalized score at 0 minutes 1  (0) 1  (0)
Normalized score at 15 minutes post-dose 1.009  (0.092) 0.901  (0.181)
Normalized score at 30 minutes post-dose 0.826  (0.104) 0.738  (0.132)
Normalized score at 60 minutes post-dose 0.786  (0.084) 0.766  (0.171)
Normalized score at 90 minutes post-dose 0.670  (0.082) 0.685  (0.16)
Normalized score at 120 minutes post-dose 0.662  (0.107) 0.709  (0.119)
Normalized score at 150 minutes post-dose 0.680  (0.101) 0.746  (0.143)
Normalized score at 180 minutes post-dose 0.645  (0.1) 0.707  (0.113)
Normalized score at 240 minutes post-dose 0.791  (0.129) 0.683  (0.112)
Normalized score at 360 minutes post-dose 0.894  (0.223) 0.122  (0.098)
2.Secondary Outcome
Title Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Hide Description Octanoic Acid is a metabolite of 1-octanol. Blood plasma levels of octanoic acid were measured at 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose.
Time Frame 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received either formulation 64 mg/kg 1-octanol in Part A or B
Arm/Group Title 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation
Hide Arm/Group Description:
Subjects fasted overnight for 6 hours. At 6AM subjects received 64 mg/kg of the 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.
Subjects fasted overnight for 6 hours. At 6AM subjects received 64 mg/kg of the 1-octanol in 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).
Overall Number of Participants Analyzed 12 12
Mean (Standard Deviation)
Unit of Measure: ng/ml
Plasma Octanoic Acid Level at 5 min post-dose 62.94  (29.37) 74.16  (38.78)
Plasma Octanoic Acid Level at 20 min post-dose 5064.12  (4240.79) 3885.52  (4111.65)
Plasma Octanoic Acid Level at 45 min post-dose 7967.97  (3078.81) 9645.55  (5805.79)
Plasma Octanoic Acid Level at 70 min post-dose 6788.58  (2598.85) 13315.26  (9162.85)
Plasma Octanoic Acid Level at 100 min post-dose 5701.60  (2207.62) 9289.39  (2998.95)
Plasma Octanoic Acid Level at 130 min post-dose 5448.23  (1514.60) 9605.68  (3822.29)
Plasma Octanoic Acid Level at 160 min post-dose 4662.88  (1719.10) 6678.69  (2748.75)
Plasma Octanoic Acid Level at 210 min post-dose 3179.10  (1194.03) 4307.74  (3135.91)
Plasma Octanoic Acid Level at 270 min post-dose 2248.74  (1192.60) 2618.25  (2585.11)
Plasma Octanoic Acid Level at 360 min post-dose 1266.37  (822.56) 872.51  (758.44)
3.Secondary Outcome
Title Heart Rate Post 1-Octanol Dose
Hide Description [Not Specified]
Time Frame 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of 1-octanol in Part A, B or C
Arm/Group Title 1-Octanol Dose
Hide Arm/Group Description:
Subjects fasted overnight for 6 hours. At 6AM subjects received 1-128 mg/kg of the 1-octanol
Overall Number of Participants Analyzed 15
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute
Heart Rate at 0 min 70.8  (2.9)
Heart Rate at 15 min 66.6  (2.7)
Heart Rate at 100 min 67.1  (2.7)
Heart Rate at 24 hours 72.4  (2.7)
4.Secondary Outcome
Title PR and QTc Intervals Post 1-Octanol Dose
Hide Description [Not Specified]
Time Frame 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of 1-octanol in Part A, B or C
Arm/Group Title 1-Octanol Dose
Hide Arm/Group Description:
Subjects fasted overnight for 6 hours. At 6AM subjects received 1-128 mg/kg of 1-octanol
Overall Number of Participants Analyzed 15
Least Squares Mean (Standard Error)
Unit of Measure: ms
PR Interval at 0 min 168.8  (6.6)
PR Interval at 15 min 172.8  (6.2)
PR Interval at 100 min 171.6  (6.2)
PR Interval at 24 hours 168.6  (6.2)
QTc Interval at 0 min 433.8  (8.4)
QTc Interval at 15 min 436.5  (7.4)
QTc Interval at 100 min 433.0  (7.4)
QTc Interval at 24 hours 437.4  (7.5)
Time Frame 6 hours
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1-octanol Dose
Hide Arm/Group Description Subjects fasted overnight for 6 hours. At 6AM subjects received 1-128 mg/kg of 1-octanol
All-Cause Mortality
1-octanol Dose
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
1-octanol Dose
Affected / at Risk (%) # Events
Total   2/15 (13.33%)    
Infections and infestations   
Fever * [1]  1/15 (6.67%)  1
Injury, poisoning and procedural complications   
Fall * [2]  1/15 (6.67%)  1
*
Indicates events were collected by non-systematic assessment
[1]
due to flu
[2]
leading to fracture of one rib, accidental nature (patient slipped)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1-octanol Dose
Affected / at Risk (%) # Events
Total   14/15 (93.33%)    
Cardiac disorders   
Hypotension   1/15 (6.67%)  1
Eye disorders   
Blurred Vision   1/15 (6.67%)  1
Dry Eyes   1/15 (6.67%)  5
Gastrointestinal disorders   
Taste Change   8/15 (53.33%)  12
Heartburn   5/15 (33.33%)  7
Gas/Bloating   5/15 (33.33%)  8
Nausea   4/15 (26.67%)  7
Dry Mouth   4/15 (26.67%)  6
Constipation   3/15 (20.00%)  6
Diarrhea   2/15 (13.33%)  2
General disorders   
Headache   5/15 (33.33%)  10
Sedation   2/15 (13.33%)  3
Dizziness   2/15 (13.33%)  5
Insomnia   1/15 (6.67%)  1
Sweating   1/15 (6.67%)  1
Nervous system disorders   
Worsening of tremor   2/15 (13.33%)  5
Numbness   1/15 (6.67%)  1
Vertigo   1/15 (6.67%)  1
Fainting   1/15 (6.67%)  1
Psychiatric disorders   
Anxiety   2/15 (13.33%)  2
Respiratory, thoracic and mediastinal disorders   
Cough   2/15 (13.33%)  2
Indicates events were collected by systematic assessment
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.
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
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
First Submitted: January 30, 2005
First Posted: January 31, 2005
Results First Submitted: November 10, 2010
Results First Posted: February 1, 2012
Last Update Posted: February 1, 2012