Trial Outcomes & Findings for Double-Blind, Placebo Controlled Pilot Study of Octanoic Acid in Essential Tremor (NCT NCT00848172)
NCT ID: NCT00848172
Last Updated: 2012-12-27
Results Overview
Postural tremor was measured using accelerometry with a motion sensor (accelerometer) placed at the dorsum of each hand, and tremor recorded simultaneously with surface-electromyography of wrist flexors and extensors for 2 minutes at each time-point. The recording was repeated with 1 lbs weight added to each wrist, which was described to record the central tremor component. The primary outcome measure was defined as tremor power of the central tremor component (after the addition of weight) 80 minutes after administration, measured at the dominant hand, normalized to baseline (baseline = 1), and comparing octanoic acid vs. placebo. Ratio of tremor power at 80 min divided by tremor power at baseline used for outcome measure calculation.
COMPLETED
PHASE1/PHASE2
29 participants
80 min after administration of the study drug on day 1 and 2 of Visit 2
2012-12-27
Participant Flow
Subjects with a diagnosis of ET were recruited by referral from the Motor Control outpatient clinic, a listing on the NINDS web page, and from the general community.
29 subjects (12f, 17m) were screened for eligibility. 10 subjects were considered screening failures due to the following reasons: failure to confirm ET according to diagnostic consensus criteria (n=7), other medical conditions precluding a safe participation (n=2), or the lack of objective alcohol-response (n=1). Nineteen subjects were randomized.
Participant milestones
| Measure |
Sequence OA / Placebo
During the 3-day inpatient Visit 2 (Drug Administration), after the admissions day (day 1 of Visit 2) patients randomized to Sequence OA / Placebo received a single oral dose of 4 mg/kg OA on the second day of Visit 2, and matching Placebo on the third day of Visit 2. Patients were discharged at the end of the third day of Visit 2, which ended this study visit.
|
Sequence Placebo / OA
During the 3-day inpatient Visit 2 (Drug Administration), after the admissions day (day 1 of Visit 2) patients randomized to Sequence OA / Placebo received Placebo on the second day of Visit 2, and a single oral dose of 4 mg/kg OA on the third day of Visit 2. Patients were discharged at the end of the third day of Visit 2, which ended this study visit.
|
|---|---|---|
|
Visit 2 - Drug Administration
STARTED
|
10
|
9
|
|
Visit 2 - Drug Administration
COMPLETED
|
10
|
8
|
|
Visit 2 - Drug Administration
NOT COMPLETED
|
0
|
1
|
|
Visit 3 - Follow Up
STARTED
|
10
|
8
|
|
Visit 3 - Follow Up
COMPLETED
|
10
|
8
|
|
Visit 3 - Follow Up
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Double-Blind, Placebo Controlled Pilot Study of Octanoic Acid in Essential Tremor
Baseline characteristics by cohort
| Measure |
Sequence OA / Placebo
n=10 Participants
First day: octanoic acid Second day: placebo
|
Sequence Placebo / OA
n=9 Participants
First day: placebo Second day: octanoic acid
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age Continuous
|
59.90 years
STANDARD_DEVIATION 10.97 • n=5 Participants
|
64.22 years
STANDARD_DEVIATION 8.60 • n=7 Participants
|
61.95 years
STANDARD_DEVIATION 9.90 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
9 participants
n=7 Participants
|
19 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 80 min after administration of the study drug on day 1 and 2 of Visit 2Population: 2 patients were excluded from primary outcome measure analysis because of one subject was withdrawn prior to drug administration due to an SAE, and one subject did not exhibit a central tremor component (primary measure), on the day of administration.
Postural tremor was measured using accelerometry with a motion sensor (accelerometer) placed at the dorsum of each hand, and tremor recorded simultaneously with surface-electromyography of wrist flexors and extensors for 2 minutes at each time-point. The recording was repeated with 1 lbs weight added to each wrist, which was described to record the central tremor component. The primary outcome measure was defined as tremor power of the central tremor component (after the addition of weight) 80 minutes after administration, measured at the dominant hand, normalized to baseline (baseline = 1), and comparing octanoic acid vs. placebo. Ratio of tremor power at 80 min divided by tremor power at baseline used for outcome measure calculation.
Outcome measures
| Measure |
Octanoic Acid
n=17 Participants
|
Placebo
n=17 Participants
|
|---|---|---|
|
Normalized Accelerometric Tremor Power, Dominant Hand, 80min After Administration, Weighted Condition
|
0.669 ratio
Interval 0.489 to 1.548
|
0.798 ratio
Interval 0.54 to 1.342
|
SECONDARY outcome
Timeframe: 300 min post doseAs described at the section for the primary outcome, normalized accelerometric tremor accelerometry was measured at other time-points to describe a time-course of effect. This stated secondary outcome compared normalized (baseline = 1) accelerometric at the last time-point 300 min post dose after OA vs Placebo. Ratios of tremor power at 300 min divided by tremor power at baseline used for outcome measure calculation.
Outcome measures
| Measure |
Octanoic Acid
n=17 Participants
|
Placebo
n=17 Participants
|
|---|---|---|
|
Normalized Tremor Power, 300 Min After Administration, Weighted Condition, Dominant Hand, OA vs Placebo
|
0.689 ratio
Interval 0.506 to 1.111
|
1.071 ratio
Interval 0.542 to 1.995
|
SECONDARY outcome
Timeframe: between 5 and 300 min post doseTime to plasma peak OA
Outcome measures
| Measure |
Octanoic Acid
n=18 Participants
|
Placebo
|
|---|---|---|
|
TMax Octanoic Acid
|
72.8 min
Standard Deviation 34.3
|
—
|
SECONDARY outcome
Timeframe: 5 to 300 min post doseArea under the curve of PA plasma levels after administration
Outcome measures
| Measure |
Octanoic Acid
n=18 Participants
|
Placebo
|
|---|---|---|
|
PK: AUC After OA
|
1860.9 hr*ng/ml
Standard Deviation 474.7
|
—
|
Adverse Events
Octanoic Acid
Placebo
Non-drug Related
Serious adverse events
| Measure |
Octanoic Acid
n=18 participants at risk
|
Placebo
n=19 participants at risk
|
Non-drug Related
n=19 participants at risk
AE was considered to be non-drug related, if no temporal connection was present between AE occurrence and drug administration (e.g. if AE occurred during the study, but prior to drug-administration), or an AE was clearly related to a study procedure (e.g. PICC line) rather than the study drug.
|
|---|---|---|---|
|
Cardiac disorders
Troponin I elevation
|
0.00%
0/18
|
0.00%
0/19
|
5.3%
1/19 • Number of events 1
|
|
Blood and lymphatic system disorders
bleeding from PICC insertion site
|
0.00%
0/18
|
0.00%
0/19
|
5.3%
1/19 • Number of events 1
|
Other adverse events
| Measure |
Octanoic Acid
n=18 participants at risk
|
Placebo
n=19 participants at risk
|
Non-drug Related
n=19 participants at risk
AE was considered to be non-drug related, if no temporal connection was present between AE occurrence and drug administration (e.g. if AE occurred during the study, but prior to drug-administration), or an AE was clearly related to a study procedure (e.g. PICC line) rather than the study drug.
|
|---|---|---|---|
|
General disorders
Fatigue
|
16.7%
3/18 • Number of events 3
|
10.5%
2/19 • Number of events 2
|
0.00%
0/19
|
|
Skin and subcutaneous tissue disorders
Itching
|
5.6%
1/18 • Number of events 1
|
10.5%
2/19 • Number of events 2
|
0.00%
0/19
|
|
Nervous system disorders
Headache
|
11.1%
2/18 • Number of events 2
|
5.3%
1/19 • Number of events 1
|
0.00%
0/19
|
|
Injury, poisoning and procedural complications
Pain at PICC insertion site
|
0.00%
0/18
|
0.00%
0/19
|
10.5%
2/19 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/18
|
5.3%
1/19 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Dry Mouth
|
0.00%
0/18
|
5.3%
1/19 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Taste Change
|
5.6%
1/18 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
0.00%
0/19
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place