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

This study has been completed.

Study NCT00102596 Information provided by National Institutes of Health Clinical Center (CC)

First Received on January 30, 2005. Last Updated on January 31, 2012 History of Changes

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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.

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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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 ]

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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 ]

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3. Secondary:

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

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4. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

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
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.

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:

Nahab FB, Wittevrongel L, Ippolito D, Toro C, Grimes GJ, Starling J, Potti G, Haubenberger D, Bowen D, Buchwald P, Dong C, Kalowitz D, Hallett M. An open-label, single-dose, crossover study of the pharmacokinetics and metabolism of two oral formulations of 1-octanol in patients with essential tremor. Neurotherapeutics. 2011 Oct;8(4):753-62.

Other Publications:

Bikson M, Ghai RS, Baraban SC, Durand DM. Modulation of burst frequency, duration, and amplitude in the zero-Ca(2+) model of epileptiform activity. J Neurophysiol. 1999 Nov;82(5):2262-70.

Busenbark KL, Nash J, Nash S, Hubble JP, Koller WC. Is essential tremor benign? Neurology. 1991 Dec;41(12):1982-3.

Bushara KO, Goldstein SR, Grimes GJ Jr, Burstein AH, Hallett M. Pilot trial of 1-octanol in essential tremor. Neurology. 2004 Jan 13;62(1):122-4.

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