Trial Outcomes & Findings for Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor (NCT NCT00102596)
NCT ID: NCT00102596
Last Updated: 2012-02-01
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose
Results posted on
2012-02-01
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Part A
STARTED
|
11
|
0
|
|
Part A
Participants Assigned Treatment
|
5
|
0
|
|
Part A
COMPLETED
|
4
|
0
|
|
Part A
NOT COMPLETED
|
7
|
0
|
|
Part B
STARTED
|
0
|
10
|
|
Part B
COMPLETED
|
0
|
10
|
|
Part B
NOT COMPLETED
|
0
|
0
|
|
Part C
STARTED
|
0
|
2
|
|
Part C
COMPLETED
|
0
|
2
|
|
Part C
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|
|
Part A
Screen failures
|
6
|
0
|
|
Part A
Adverse Event
|
1
|
0
|
Baseline Characteristics
Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
Baseline characteristics by cohort
| Measure |
All Participants
n=15 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
|
|---|---|
|
Age Continuous
|
68.1 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
|
Height
|
169.6 centimeters
STANDARD_DEVIATION 12.0 • n=5 Participants
|
|
Weight
|
82.9 kg
STANDARD_DEVIATION 20.1 • n=5 Participants
|
|
Body Mass Index
|
28.6 kg/m^2
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Age of onset
|
39.5 years
STANDARD_DEVIATION 18.6 • n=5 Participants
|
|
Disease Duration
|
28.7 years
STANDARD_DEVIATION 17.2 • n=5 Participants
|
|
History of alcohol-responsive tremors
|
15 participants
n=5 Participants
|
|
Number of alcohol servings required for tremor response
|
2.1 servings
STANDARD_DEVIATION 0.3 • n=5 Participants
|
|
Family history of essential tremor
|
13 participants
n=5 Participants
|
|
Fahn Tolosa Marin Tremor Rating Scale
|
41.6 scores on a scale
STANDARD_DEVIATION 17.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dosePopulation: All participants who received both formulations of 64 mg/kg 1-octanol in Part B
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.
Outcome measures
| Measure |
64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation
n=10 Participants
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.
|
64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation
n=10 Participants
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).
|
|---|---|---|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 30 minutes post-dose
|
0.826 normalized score on a scale
Standard Error 0.104
|
0.738 normalized score on a scale
Standard Error 0.132
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 0 minutes
|
1 normalized score on a scale
Standard Error 0
|
1 normalized score on a scale
Standard Error 0
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 15 minutes post-dose
|
1.009 normalized score on a scale
Standard Error 0.092
|
0.901 normalized score on a scale
Standard Error 0.181
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 60 minutes post-dose
|
0.786 normalized score on a scale
Standard Error 0.084
|
0.766 normalized score on a scale
Standard Error 0.171
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 90 minutes post-dose
|
0.670 normalized score on a scale
Standard Error 0.082
|
0.685 normalized score on a scale
Standard Error 0.16
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 120 minutes post-dose
|
0.662 normalized score on a scale
Standard Error 0.107
|
0.709 normalized score on a scale
Standard Error 0.119
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 150 minutes post-dose
|
0.680 normalized score on a scale
Standard Error 0.101
|
0.746 normalized score on a scale
Standard Error 0.143
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 180 minutes post-dose
|
0.645 normalized score on a scale
Standard Error 0.1
|
0.707 normalized score on a scale
Standard Error 0.113
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 240 minutes post-dose
|
0.791 normalized score on a scale
Standard Error 0.129
|
0.683 normalized score on a scale
Standard Error 0.112
|
|
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Normalized score at 360 minutes post-dose
|
0.894 normalized score on a scale
Standard Error 0.223
|
0.122 normalized score on a scale
Standard Error 0.098
|
SECONDARY outcome
Timeframe: 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dosePopulation: All participants who received either formulation 64 mg/kg 1-octanol in Part A or B
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.
Outcome measures
| Measure |
64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation
n=12 Participants
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.
|
64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation
n=12 Participants
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).
|
|---|---|---|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 5 min post-dose
|
62.94 ng/ml
Standard Deviation 29.37
|
74.16 ng/ml
Standard Deviation 38.78
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 20 min post-dose
|
5064.12 ng/ml
Standard Deviation 4240.79
|
3885.52 ng/ml
Standard Deviation 4111.65
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 45 min post-dose
|
7967.97 ng/ml
Standard Deviation 3078.81
|
9645.55 ng/ml
Standard Deviation 5805.79
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 70 min post-dose
|
6788.58 ng/ml
Standard Deviation 2598.85
|
13315.26 ng/ml
Standard Deviation 9162.85
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 100 min post-dose
|
5701.60 ng/ml
Standard Deviation 2207.62
|
9289.39 ng/ml
Standard Deviation 2998.95
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 130 min post-dose
|
5448.23 ng/ml
Standard Deviation 1514.60
|
9605.68 ng/ml
Standard Deviation 3822.29
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 160 min post-dose
|
4662.88 ng/ml
Standard Deviation 1719.10
|
6678.69 ng/ml
Standard Deviation 2748.75
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 210 min post-dose
|
3179.10 ng/ml
Standard Deviation 1194.03
|
4307.74 ng/ml
Standard Deviation 3135.91
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 270 min post-dose
|
2248.74 ng/ml
Standard Deviation 1192.60
|
2618.25 ng/ml
Standard Deviation 2585.11
|
|
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Plasma Octanoic Acid Level at 360 min post-dose
|
1266.37 ng/ml
Standard Deviation 822.56
|
872.51 ng/ml
Standard Deviation 758.44
|
SECONDARY outcome
Timeframe: 0 minutes, 15 minutes, 100 minutes and 24 hours post-dosePopulation: All participants who received at least 1 dose of 1-octanol in Part A, B or C
Outcome measures
| Measure |
64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation
n=15 Participants
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.
|
64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation
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).
|
|---|---|---|
|
Heart Rate Post 1-Octanol Dose
Heart Rate at 0 min
|
70.8 beats per minute
Standard Error 2.9
|
—
|
|
Heart Rate Post 1-Octanol Dose
Heart Rate at 15 min
|
66.6 beats per minute
Standard Error 2.7
|
—
|
|
Heart Rate Post 1-Octanol Dose
Heart Rate at 100 min
|
67.1 beats per minute
Standard Error 2.7
|
—
|
|
Heart Rate Post 1-Octanol Dose
Heart Rate at 24 hours
|
72.4 beats per minute
Standard Error 2.7
|
—
|
SECONDARY outcome
Timeframe: 0 minutes, 15 minutes, 100 minutes and 24 hours post-dosePopulation: All participants who received at least 1 dose of 1-octanol in Part A, B or C
Outcome measures
| Measure |
64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation
n=15 Participants
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.
|
64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation
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).
|
|---|---|---|
|
PR and QTc Intervals Post 1-Octanol Dose
PR Interval at 0 min
|
168.8 ms
Standard Error 6.6
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
PR Interval at 15 min
|
172.8 ms
Standard Error 6.2
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
PR Interval at 100 min
|
171.6 ms
Standard Error 6.2
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
PR Interval at 24 hours
|
168.6 ms
Standard Error 6.2
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
QTc Interval at 0 min
|
433.8 ms
Standard Error 8.4
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
QTc Interval at 15 min
|
436.5 ms
Standard Error 7.4
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
QTc Interval at 100 min
|
433.0 ms
Standard Error 7.4
|
—
|
|
PR and QTc Intervals Post 1-Octanol Dose
QTc Interval at 24 hours
|
437.4 ms
Standard Error 7.5
|
—
|
Adverse Events
1-octanol Dose
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
1-octanol Dose
n=15 participants at risk
Subjects fasted overnight for 6 hours. At 6AM subjects received 1-128 mg/kg of 1-octanol
|
|---|---|
|
Infections and infestations
Fever
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Injury, poisoning and procedural complications
Fall
|
6.7%
1/15 • Number of events 1 • 6 hours
|
Other adverse events
| Measure |
1-octanol Dose
n=15 participants at risk
Subjects fasted overnight for 6 hours. At 6AM subjects received 1-128 mg/kg of 1-octanol
|
|---|---|
|
Gastrointestinal disorders
Taste Change
|
53.3%
8/15 • Number of events 12 • 6 hours
|
|
General disorders
Headache
|
33.3%
5/15 • Number of events 10 • 6 hours
|
|
Gastrointestinal disorders
Heartburn
|
33.3%
5/15 • Number of events 7 • 6 hours
|
|
Gastrointestinal disorders
Gas/Bloating
|
33.3%
5/15 • Number of events 8 • 6 hours
|
|
Gastrointestinal disorders
Nausea
|
26.7%
4/15 • Number of events 7 • 6 hours
|
|
Gastrointestinal disorders
Dry Mouth
|
26.7%
4/15 • Number of events 6 • 6 hours
|
|
Gastrointestinal disorders
Constipation
|
20.0%
3/15 • Number of events 6 • 6 hours
|
|
General disorders
Sedation
|
13.3%
2/15 • Number of events 3 • 6 hours
|
|
General disorders
Dizziness
|
13.3%
2/15 • Number of events 5 • 6 hours
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
2/15 • Number of events 2 • 6 hours
|
|
Gastrointestinal disorders
Diarrhea
|
13.3%
2/15 • Number of events 2 • 6 hours
|
|
Nervous system disorders
Worsening of tremor
|
13.3%
2/15 • Number of events 5 • 6 hours
|
|
Psychiatric disorders
Anxiety
|
13.3%
2/15 • Number of events 2 • 6 hours
|
|
General disorders
Insomnia
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Cardiac disorders
Hypotension
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Nervous system disorders
Numbness
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Nervous system disorders
Vertigo
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Nervous system disorders
Fainting
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Eye disorders
Blurred Vision
|
6.7%
1/15 • Number of events 1 • 6 hours
|
|
Eye disorders
Dry Eyes
|
6.7%
1/15 • Number of events 5 • 6 hours
|
|
General disorders
Sweating
|
6.7%
1/15 • Number of events 1 • 6 hours
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60